Volume 67 • Number S10 • October 2015
ABSTRACT SUPPLEMENT 2015 ACR/ARHP ANNUAL MEETING November 6–11, 2015 San Francisco, CA
26/09/15 2:17 PM
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Table of Contents ACR/ARHP ABSTRACT SESSIONS SUNDAY, NOVEMBER 8, 2015 8:30 AM - 4:00 PM ACR Poster Session A (#1-895) 11:00 AM - 12:30 PM ACR Plenary Session I Discovery 2015 (#896-901) 2:30 - 4:00 PM ACR Concurrent Abstract Sessions (#901-906) Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis (#907-912) Epidemiology and Public Health I: Rheumatoid Arthritis Comorbidities and Mortality (#913-918) Fibromyalgia: Insights into Diagnostic Criteria and Symptom Epidemiology (#919-924) Health Services Research I: Digital Health and Patient, Provider Factors in Rheumatic Disease (#925-930) Imaging of Rheumatic Diseases I: Ultrasound (#931-936) Innate Immunity and Rheumatic Disease (#937-942) Miscellaneous Rheumatic and Inflammatory (#943-948) Muscle Biology, Myositis and Myopathies I (#949-954) Osteoarthritis – Clinical Aspects: Treatments and Epidemiology (#955-960) Pediatric Rheumatology – Clinical and Therapeutic Aspects I: Juvenile Idiopathic Arthritis (#961-966) Rheumatoid Arthritis – Human Etiology and Pathogenesis I (#967-972) Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy I: Biologics (#973-978) Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment: Treatment of Ankylosing Spondylitis (#979-984) Spondylarthropathies Psoriatic Arthritis – Pathogenesis, Etiology (#985-990) Systemic Lupus Erythematosus – Clinical Aspects and Treatment I: Epidemiology and Prognosis (#991-996) T cell Biology and Targets in Autoimmune Disease I ARHP Concurrent Abstract Session (#997-1002) ARHP: Exemplary Abstracts 4:30 - 6:00 PM ACR Concurrent Abstract Sessions (#1003-1008) Osteoarthritis – Clinical Aspects I: Imaging and Epidemiology (#1009-1014) Education (#1015-1020) Pain: Basic Aspects (#1021-1026) Pediatric Rheumatology – Pathogenesis and Genetic (#1027-1032) Quality Measures and Quality of Care (#1033-1038) Rheumatoid Arthritis – Animal Models I
(#1039-1044) Rheumatoid Arthritis – Clinical Aspects I – Treatment Advances and Strategies (#1045-1050) Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy II: Small Molecular Targeted Therapies (#1051-1056) Sjögren’s Syndrome I: Basic Insights (#1057-1062) Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment: Clinical Aspects and CoMorbidities (#1063-1068) Systemic Lupus Erythematosus – Clinical Aspects and Treatment II: Patient-Reported Measures, Outcomes and Reporting (#1069-1074) Systemic Lupus Erythematosus – Human Etiology and Pathogenesis: Genetics, Gene Expression, and Epigenetics (#1075-1080) Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s – Clinical Aspects and Therapeutics I (#1081-1086) Vasculitis I 4:30-6:00 PM ACR/ARHP Combined Abstract Session (#1087-1092) ACR/ARHP Combined Abstract Session: Rehabilitation
MONDAY, NOVEMBER 9, 2015 8:30 AM - 4:00 PM ACR/ARHP Poster Session B (#1093-1993) 11:00 AM - 12:30 PM ACR Plenary Session II Discovery 2015 (#1994-1999) 2:30 - 4:00 PM ACR Concurrent Abstract Sessions (#2000-2005) Antiphospholipid Syndrome: Recent Findings (#2006-2011) Biology and Pathology of Bone and Joint: Osteoarthritis Pathogenesis (#2012-2017) Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II (#2018-2023) Epidemiology and Public Health II: RA and Lifestyle Factors (#2024-2029) Imaging of Rheumatic Diseases II: MRI, PET and CT (#2030-2035) Infection-related Rheumatic Disease (#2036-2041) Miscellaneous Rheumatic and Inflammatory Diseases Oral Session II (#2042-2047) Pediatric Rheumatology – Clinical and Therapeutic Aspects II: Pediatric Systemic Lupus Erythematosus (#2048-2053) Rheumatoid Arthritis (RA) – Clinical Aspects II: Infection, Malignancy and Other Comorbidites in RA (#2054-2059) Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy III: Biosimilars (#2060-2065) Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment: Clinical Aspects (#2066-2071) Systemic Lupus Erythematosus – Clinical Aspects and Treatment III: Biomarkers (#2072-2077) Systemic Lupus Erythematosus – Human Etiology and Pathogenesis: Modulators of Disease
ARHP Concurrent Abstract Session (#2078-2083) ARHP II: Lupus 4:30 - 6:00 PM ACR Concurrent Abstract Sessions (#2084-2089) Biology and Pathology of Bone and Joint: Bone Remodeling (#2090-2095) Epidemiology and Public Health III: Risk Factors, Treatment and Outcomes of Gout and Osteoarthritis (#2096-2101) Genetics, Genomics, and Proteomics (#2102-2107) Health Services Research II: Rheumatoid Arthritis Treatment and Healthcare Utilization (#2108-2113) Metabolic and Crystal Arthropathies I: Therapeutics (#2114-2119) Orthopedics, Low Back Pain and Rehabilitation (#2120-2125) Reproductive Issues in Rheumatic Disorders: Basic and Clinical Aspects (#2126-2131) Rheumatoid Arthritis – Clinical Aspects III: Cardiovascular Disease and RA (#2132-2137) Rheumatoid Arthritis – Human Etiology and Pathogenesis II (#2138-2143) Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy IV: Safety of Targeted Therapies (#2144-2149) Spondylarthropathies (SpA) and Psoriatic Arthritis (PsA) – Clinical Aspects and Treatment: Treatment of PsA and SpA (#2150-2155) Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics I (#2156-2161) Vasculitis II ACR/ARHP Combined Abstract Session (#2162-2167) ACR/ARHP Combined Abstract Session: Epidemiology and Pubic Health ARHP Concurrent Abstract Session (#2168-2173) ARHP III: Epidemiology and Public Health
TUESDAY, NOVEMBER 10, 2015 8:30 AM - 4:00 PM ACR/ARHP Poster Session C (#2174-3073) 11:00 AM - 12:30 PM ACR Plenary Session III Discovery 2015 (#3074-3079) 2:30 - 4:00 PM ACR Concurrent Abstract Sessions (#3080-3085) 2015 Rheumatology Research Foundation Edmond L. Dubois, MD Memorial Lectureship: Systemic Lupus Erythematosus – Basic Science (#3086-3091) Fibromyalgia: Clinical Issues (#3092-3097) Pediatric Rheumatology – Clinical and Therapeutic Aspects III: Miscellaneous Pediatric Rheumatic Diseases (#3098-3013) Rheumatoid Arthritis – Clinical Aspects IV: Biomarkers, Disease Progression and Treatment Response (#3104-3109) Rheumatoid Arthritis – Human Etiology and Pathogenesis III (#3110-3115) Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy V: Immunogenecity
(#3116-3121) Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment: Psoriatic Arthritis – Comorbidities (#3122-3127) Systemic Lupus Erythematosus – Clinical Aspects and Treatment V: Neuropsychiatric Lupus (#3128-3133) Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics II (#3134-3139) Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s – Clinical Aspects and Therapeutics II (#3140-3145) Vasculitis III ACR/ARHP Combined Abstract Session (#3146-3151) ACR/ARHP Combined Abstract Session: Pediatric Rheumatology 4:30 - 6:00 PM ACR Concurrent Abstract Session (#3152-3157) B Cell Biology and Targets in Autoimmune Disease: Novel B Cell roles in Rheumatoid Arthritis and Systemic Lupus Erythematosus (#3158-3163) Epidemiology and Public Health IV: Risk Factors and Comorbidities for Systemic Lupus Erythematosus and Psoriatic Arthritis (#3164-3169) Metabolic and Crystal Arthropathies II: Mechanisms and Associations (#3170-3175) Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis I (#3176-3181) Pediatric Rheumatology – Clinical and Therapeutic Aspects IV: Imaging and Novel Clinical Interventions (#3182-3187) Rheumatoid Arthritis – Clinical Aspects V: Goal = Remission (#3188-3193) Rheumatoid Arthritis Animal Models II (#3194-3199) Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy VI: Strategies (#3200-3205) Sjögren’s Syndrome II: Clinical Discoveries (#3206-3211) Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment: Clinical Aspects, Imaging and Biomarkers (#3212-3217) Systemic Lupus Erythematosus–Animal Models (#3218-3223) Systemic Lupus Erythematosus–Clinical Aspects and Treatment VI: Novel Therapies (#3224-3229) Vasculitis IV ARHP Concurrent Abstract Session (#3230-3235) ARHP IV: Clinical Practice and Patient Care
WEDNESDAY, NOVEMBER 11, 2015 9:00-10:30 AM ACR Concurrent Abstract Sessions (#3236-3246) Rheumatoid Arthritis (RA) – Clinical Aspects VI: Death Be Not Proud – Mortality and Treatment Outcomes in RA (Includes 2014 Lee C. Howley, Sr. Prize for Arthritis Research Introductory Talk) ARHP Concurrent Abstract Session (#3241-3246) ARHP V: Physical Activity 11:00 AM - 12:30 PM ACR Concurrent Abstract Sessions (#3247-3252) Pain: Clinical Aspects
(#3253-3258) Rheumatoid Arthritis – Clinical Aspects VII: Disease Activity and Updates in Measurement (#3259-3264) Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s – Clinical Aspects and Therapeutics III ARHP Concurrent Abstract Session (#3265-3270) ARHP VI: Physical Function and Disability
ACR LATE-BREAKING ABSTRACT SESSIONS TUESDAY, NOVEMBER 10, 2015 8:30 AM - 4:00 PM ACR/ARHP Poster Session C (#7L-15L) ACR Late-breaking Abstract Poster Presentations* 4:30 - 6:00 PM ACR Concurrent Abstract Session (#1L-6L) ACR Late-breaking Abstract Oral Presentations* *Please Note: ACR Late-breaking abstracts are listed below in numberic order instead of presentation order.
Abstract Number: 1
The Integrin Very Late Antigen-4 Plays a Key Role in the Recruitment of B Cells at the Inflammatory Foci Estefanía Armas-González 1, Ana Díaz-Martín2, María Jesús Domínguez-Luis3, María Teresa Arce-Franco2 and Federico Díaz-González4, 1Universidad de La Laguna, Pharmacology Department, Tenerife, Spain, 2Hospital Universitario de Canarias, Rheumatology Service, Tenerife, Spain, 3CIBICAN, Center of Biomedical Research of the Canary Islands, University of La Laguna, Tenerife, Spain, 4Investigation Unit, Sociedad Española de Reumatológía, Madrid, Spain First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Experimental data suggest that B cells must migrate and accumulate into the synovial membrane to exert their pathogenic role in rheumatoid arthritis (RA). Leukocyte extravasation requires a number of coordinated adhesives events between circulating leukocytes and endothelial cells, a process known as the adhesion cascade. While the molecules involved in the sequential steps of the adhesion cascade for neutrophils and T lymphocytes have been well established, little is known about this process in B cells. Objective: To determine the adhesion molecules involved in the interactions between B cells and endothelium under dynamic condition resembling those of postcapillary venules during the inflammatory response. Methods: The surface expression levels of very late antigen (VLA)-4, intercellular adhesion molecule (ICAM)-1 and L-selectin were assessed by double-colour staining flow cytometry analysis in CD20 + cells from the peripheral blood (PB) and synovial fluid (SF), simultaneously obtained from 10 RA and 8 psoriatic arthritis (PsA) patients. Dynamic interactions between B cells negatively immunoselected from buffy coats, and 12h TNF-a-activated human umbilical vein endothelial cell (HUVEC) monolayers were studied in a two-parallel plate flow chamber. To study molecules involved in the B-cells-HUVEC dynamic interaction, B cells were preincubated with monoclonal antibodies (mAbs) anti-CD20 or blocking mAbs anti- L-selectin, VLA-4 and ICAM-1; and HUVEC, with anti-vascular adhesion molecule (VCAM)1. Results: Flow cytometry analysis showed that the VLA-4 surface expression level in B-cells from SF in both RA (105±30%) and PsA (135±45%) patients was not significantly different with respect to PB (considered 100%). Interestingly, the surface expression level of ICAM-1 was significantly higher in SF relative to PB, in both RA (280±85%;) and PsA (300±65%) patients, while L-selectin surface expression diminished in SF compared to PB in RA (40±5%) and PsA (45±5%). In flow chamber experiments, no differences were observed in the process of rolling when B cells were incubated with anti-CD20 antibodies, or with blocking mAbs anti-L-selectin and anti-ICAM-1 with respect to cells incubated with mAb matching controls. However, the presence of blocking anti-VLA-4 mAb or anti-VCAM-1 mAbs abrogated the interaction of B cells with activated endothelial cells. Conclusion:
These results suggest that 1) B-cells with increased ICAM-1 expression and decreased L-selectin expression are preferentially recruited in the inflamed synovial microenvironment; and 2) the integrin VLA-4, vis-à-vis its endothelial counter receptor VCAM-1, plays a key role in the initial process of B-cell extravasation to inflammatory foci. Disclosure: E. Armas-González, None; A. Díaz-Martín, None; M. J. Domínguez-Luis, None; M. T. Arce-Franco, None; F. Díaz-González, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-integrin-very-late-antigen-4plays-a-key-role-in-the-recruitment-of-b-cells-at-the-inflammatory-foci
Abstract Number: 2
The Neutrophil Protein S100A12 Has Stronger Associations with a Comprehensive Ultrasound Score of Synovitis Than Vascular Endothelial Growth Factor in a Longitudinal Study of Rheumatoid Arthritis Patients Hilde Haugedal Nordal1,2 and Hilde Berner Hammer3, 1Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway, 2Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, 3Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: S100A12, a neutrophil protein, has proinflammatory effects on immune cells and can activate endothelial cells. The mechanism of action suggests vascular endothelial growth factor (VEGF) as a marker of synovial neovascularization in rheumatoid arthritis (RA). S100A12 and VEGF have both been associated with disease activity in RA. We wanted to compare S100A12 and VEGF as biomarkers in a large longitudinal study of RA patients, and explore their association with inflammatory activity expressed as synovial power Doppler (PD) scores. Methods: A total of 141 patients with RA (all met the ACR 1987 criteria, 81% women, mean (SD) age 52 (12) years, 79% antiCCP positive) were examined clinically and with ultrasound (US) before starting biologic treatment (67% anti-tumor necrosis factor therapy) and after 1, 2, 3, 6 and 12 months. Inflammation of wrist (radiocarpal, intercarpal, radioulnar), metacarpophalangeals 1-5, proximal interphalangeals 2-3, elbow, knee, ankle, metatarsophalangeals 1-5, extensor carpi ulnaris and tibialis posterior tendons bilaterally, expressed as gray scale (GS) and PD scores, was scored semiquantitatively 0-3. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were analyzed by in-house methodology. Sera from all examinations were frozen at -80 ˚C and S100A12 was analyzed by an enzyme-linked immunosorbent assay and VEGF by multiplex analysis. A total of 141 blood donors were controls (81% women, mean (SD) age 52 (12) years). Mann-Whitney test was used to evaluate differences between patients and controls, Wilcoxon signed rank test to study changes from baseline and Spearman’s rank test for correlation analysis. Results:
At baseline, median (interquartile range) values of S100A12 were 275 (142-463) ng/mL in patients and 129 (75-222) ng/mL in controls (p 300 mg daily) to reach a goal SUA. Of these SNVs, rs34929837 is an exonic missense mutation affecting XO (Lys395Met) and lies in the Flavin adenine nucleotide (FAD) domain of the enzyme. Rs45612738 is a synonymous codon in XO (Gly378=). All other SNVs were intronic with the majority in XO. For the secondary outcome, 1 SNV was associated with a smaller change in SUA with a lower XOI dose: rs6760292 (p < 0.05). This SNV is intronic and located in XO. Four SNVs were associated with larger changes in SUA with febuxostat 80 mg daily (all p < 0.05): rs7599556, rs75995567, rs145877467, and rs78467837. Both rs145877467 and rs78467837 are synonymous codons in AOX1(Pro1245= and Ser1264= respectively). Conclusion: Though the sample size is modest, we identified multiple SNVs that were associated with a lower XOI dose and one related to a higher XOI dose to reach a goal SUA. One of the exonic alleles detected, rs34929837, leads
to an amino acid substitution in the FAD co-factor domain of xanthine oxidase. Additional work is needed to assess the impact of this change but our data may start to explain why some patients need different doses of XOI and yet achieve the same serum uric acid (SUA) goal. Disclosure: M. Carroll, None; K. Cook, None; T. Shaak, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genomic-sequencing-of-uric-acidmetabolizing-and-clearing-genes-in-relationship-to-xanthine-oxidase-inhibitor-dose
Abstract Number: 98
The Mitochondrial DNA (mtDNA) Haplogroups Influence the Risk of Incidence Knee OA. Replication Study Including Data from Check and OAI Cohorts Ignacio Rego-Pérez 1, Angel Soto-Hermida1, Juan Fernandez-Tajes1, Mercedes Fernandez Moreno1, Maria Eugenia Vazquez Mosquera1, Estefanía Cortés-Pereira1, Sonia Pertega2, Sara Relaño-Fernandez1, Natividad Oreiro1, Carlos Fernandez-Lopez1 and Francisco J. Blanco1, 1Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, 2Unidad de Epidemiología Clínica y Bioestadística. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Genetics, Genomics and Proteomics Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Previous studies showed a significant influence of the mtDNA haplogroups on prevalence, radiographic progression and cartilage integrity of knee OA patients from different worldwide cohorts. The aim of this study is to analyze the influence of the mitochondrial variants on the risk of incident knee OA in patients from CHECK as well as in an updated cohort of OAI patients. Methods: We assessed the mtDNA haplogroups in 1003 DNA samples from CHECK and 3681 Caucasian samples from the OAI. Incident knee OA was defined as a KL score 3 months of back pain and age of onset ≤45 years were referred to the program. Exclusion criteria included: leg dominant pain, neurological symptoms, or an established diagnosis of an inflammatory condition. A comprehensive examination was completed by an Advanced Practice Physiotherapist (APP). Investigations included: HLA B27, CRP, ESR, and radiographs of the SI joints. Patients completed an initial assessment with an APP and were subsequently reviewed by a Rheumatologist with experience in axSpA. The APP and Rheumatologist independently categorized each patient’s risk of axSpA into ‘low’, ‘medium’, or ‘high’ as well as the risk of mechanical back pain. Each patient’s radiographs were interpreted independently by the APP and the Rheumatologist. Final axSpA diagnosis was determined by the Rheumatologist using the Assessment of Spondyloarthritis (ASAS) criteria. Results: A total of 123 patients were evaluated using the inter-professional MOC. Fifty-nine percent were female, with a mean age of 35.5 years (±9.6 years). Mean duration of back pain was 7.2 years (+/-8.5, range 3 months to 37 years). Agreement of risk categorization between APP and Rheumatologist was 79.7%, with Kappa coefficient= 0.57 (CI 0.380.77). Sensitivity and specificity for the APP (versus final diagnosis) was 71.4% (CI 30.3-94.9%) and 75% (CI 61.984.9%) respectively; with a positive predictive value of 25% (CI 9.6-49.4%) and negative predictive value of 95.7% (CI 84.3-99.3%). Radiographic interpretation for the presence of sacroiliitis, as per modified New York Criteria (mNYC), was fair to moderate (Kappa=0.39 left, Kappa=0.42 right) between the APP and Rheumatologist. Patients assigned by the APP and Rheumatologist to the low and high risk groups did not differ with respect to the following:
age, gender, inflammatory back pain, extra articular features, family history, HLA B27 status, ESR, CRP, or radiographic sacroiliitis. Conclusion: Using the ASAS criteria and Rheumatologists’ final diagnosis as a gold standard, an inter-professional MOC demonstrated high negative predictive value and fair agreement with radiographic interpretation for sacroiliitis consistent with the literature. No significant differences were identified between clinical characteristics when assigning risk scores for axSpA. These preliminary findings suggest that an inter-disciplinary team is an effective MOC when screening for axSpA and represents a possible model for earlier detection within primary care. Disclosure: C. Hawke, None; L. Passalent, None; A. V. Perruccio, None; K. Sundararajan, None; N. Haroon, None; R. D. Inman, None; Y. R. Rampersaud, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/axial-spondyloarthritis-validationof-an-inter-professional-model-of-care
Abstract Number: 135
Limitations of Treat-to-Target in Rheumatoid Arthritis: Joint Damage Appears As Severe As Inflammation in Contemporary Care at One Site Theodore Pincus1, Alex D. Luta2, Isabel Castrejón1, Annie Huang1, Ruchi Jain1, Sarah L. Everakes3 and Joel A. Block4, 1Rheumatology, Rush University Medical Center, Chicago, IL, 2Georgetown University, Washington, DC, 3Internal Medicine, Rush University Medical Center, Chicago, IL, 4Rush University Medical Center, Chicago, IL First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Treatment of rheumatoid arthritis is directed to “treat-to-target,” with intensification of therapy in patients with moderate/high disease activity according to a quantitative index toward low disease activity or remission. However, remission or even low disease activity is unusual in even 50% of patients. One study suggests a partial explanation, as about 20% of patients with high index scores whose therapy is not intensified had clinically important joint damage (1). We analyzed physician estimates of inflammation and damage in RA patients in two ways: a) quantitative physician 0-10 visual analog scales (VAS); and b) estimates of the proportion(s) of clinical management decisions attributable to inflammation, damage, and/or distress, totaling 100%. Methods: All patients seen at a one academic site completed an MDHAQ/RAPID3, and rheumatologists completed a RheuMetric physician checklist which includes 4 0-10 VAS for overall global estimate, inflammation, damage, and distress. A second type of scale asks doctors to estimate the proportion of the decision concerning management that is attributable to inflammation, damage, or distress, totaling 100%. Only the inflammation and damage VAS and proportions are analyzed in this study. Cross tabulations were computed with categories 0-1.9, 2-3.9,4-5.9,6-7.9,and 810 for the 0-10 VAS, and 0-19%, 20-39%, 40-59% 60-79%, and 80-100% for the proportion of the decision attributable to inflammation or damage. Results: Among 72 patients studied, a 0-10 inflammation VAS was estimated as 8-10 in 6% of patients, versus 6-7.9 in 4%, 4-5.9 in 14%, 2-3.9 in 38%, and 0-1.9 in 39% of patients. Overall, only 24% of patients had scores ≥4 for
inflammation. Damage was estimated at 8-10 in 10% of patients, 6-7.9 in 10%, 4-5.9 in 18%, 2-3.9 in 40%, and 0-1.9 in 22%; 37% of patients had damage scores ≥4 . The proportion of clinical management attributable to inflammation was estimated as 80-100% in 10% of patients, 60-79% in 15%, 40-59% in 24%, 20-39% in 18%, and 0-19% in 33%. Damage was estimated as impacting 80-100% of the clinical decision in 36%, 60-79% in 8%, 40-59% in 24%, 2039% in 18%, and 0-19% in 14% of patients. Overall, inflammation accounted for more than 40% of clinical decisions in 49% of patients, while damage accounted for more than 40% of decisions in 68% of patients. Conclusion: In one setting, damage appears to impact clinical decisions in contemporary treatment of patients with RA as much as inflammation. This finding may explain in part why clinical trials of established patients indicate only 60% ACR20 responses with all 10 approved biological agents for RA, and may also explain in part why fewer patients than might be expected are in remission. The data suggest that quantitative assessment of physician VASs to assess inflammation and damage (and distress) may be informative in routine care. Reference: 1)Tymms K, et al. Arthritis Care Res (Hoboken). 2014;66(2):190-6. Table: Physician estimates for inflammation and damage in patients with rheumatoid arthritis according to 0-10 visual analog scales and estimates of the proportion of management decisions based on these types of clinical problems Physician 0-10 VAS Score for Inflammation (Reversible) 8-10 6-7.9 4-5.9 2-3.9 0-1.9 Total 8-10 1 0 2 2 2 7 (10%) Physician 0-10 6-7.9 0 1 0 4 2 7 (10%) VAS Score for 4-5.9 1 1 1 4 6 13 (18%) Damage 2-3.9 1 0 3 13 12 29 (40%) 1 1 4 4 6 16 (22%) (irreversible) 0-1.9 Total 4 (6%) 3 (4%) 10 (14%) 27 (38%) 28 (39%) 72 (100%) % of Clinical Management Based on Inflammation 80-100% 60-79% 40-59% 20-39% 0-19% Total 80-100% NA NA NA 7 19 26 (36%) 60-79% NA NA 3 3 0 6 (8%) % of Clinical 40-59% NA 2 12 3 0 17 (24%) Management 20-39% 1 7 2 0 3 13 (18%) Based on Damage 0-19% 6 2 0 0 2 10 (14%) Total 7 (10%) 11 (15%) 17 (24%) 13 (18%) 24 (33%) 72 (100%) Disclosure: T. Pincus, None; A. D. Luta, None; I. Castrejón, None; A. Huang, None; R. Jain, None; S. L. Everakes, None; J. A. Block, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/limitations-of-treat-to-target-inrheumatoid-arthritis-joint-damage-appears-as-severe-as-inflammation-in-contemporary-care-at-one-site
Abstract Number: 136
Physician Patterns of Patient Care in Systemic Lupus Erythematosus: Are We Ordering Unnecessary Tests? Aman Kugasia1, Meenakshi Jolly2, Winston Sequeira3, Ailda Nika3, Neha Sehgal4 and Mary Dollear5, 1Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, 2Department of Medicine, Section of Rheumatology, Rush University Medical Center, Chicago, IL, 3Rheumatology, Rush University Medical Center, Chicago, IL, 4Indiana University- Bloomington, Valparaiso, IN, 5Vice President, Lupus Society of Illinois, Chicago, IL First publication: September 29, 2015
SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: To plan a quality improvement project, we need to understand the practice patterns of physicians. We undertook an online survey of physicians (MDs) (Rheumatologists, Nephrologists and General practitioner) taking care of SLE patients through the Lupus Society of Illinois (LSI) to determine the patterns of medical care provided to SLE patients. Methods: A 13-item survey was designed to collect data using item development guidelines for surveys. A cover letter explaining the study purpose, improving patient care, was emailed by LSI, and included the link to the survey. This was sent electronically to Rheumatologists and Nephrologists. All data obtained were tabulated; descriptive and stratified data were analyzed using chi square tests and p²0.05 on two-tailed tests. Results: 86 MD's completed the survey, 97% were Rheumatologists; 46 MDs practiced in academic setting, 27 in private practice, and the remainder in both settings. Mean (SD) age was 55 (12) years. Descriptives for the whole group and stratified by academic or private practice are shown in Table 1. Laboratory tests ordered at each follow up visit were significantly different among academicians as compared to private practice MD's (Table 1). In 8-11% of patients seen in private practice, the laboratory tests ordered routinely at each SLE patient care visit may be unnecessary or avoidable. Conclusion: There may be avoidable costs associated with laboratory tests ordered at each SLE patient care visit. Physician education about indications for serial routine testing for ANA, ENA and Sjogrens autoantibodies may be indicated to reduce health care costs.
Disclosure: A. Kugasia, None; M. Jolly, Pfizer Inc, 7; W. Sequeira, None; A. Nika, None; N. Sehgal, None; M. Dollear, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/physician-patterns-of-patient-carein-systemic-lupus-erythematosus-are-we-ordering-unnecessary-tests
Abstract Number: 137
Willingness to Pay for Highly Effective Drug Treatments in Brazilian Rheumatoid Arthritis Patients Cleandro Albuquerque1, Pedro Haddad2, Vander Fernandes3, Claudia Marques4, Sonia Fialho5, Adriana Kakehasi6, Fabio Jennings7, Claiton Brenol8, Lícia M. H. Mota9,10, Geraldo Castelar-Pinheiro2,11, Angela Duarte12, Iara Giroto13, Maria Raquel C. Pinto14, Mariana Toni15, Mirhelen Mendes Abreu16 and Marcos B. Ferraz17,
1Rheumatology, Hospital Universitário de Brasília - UnB, Brasília, Brazil, 2Universidade do Estado do Rio de Janeiro - UERJ, Rio de Janeiro, Brazil, 3Universidade de Cuiabá, Cuiaba MT, Brazil, 4Disciplina de Reumatologia, Hospital
das Clínicas - Universidade Federal de Pernambuco, Recife - PE, Brazil, 5Rodovia Virgílio Várzea 1510 B, Universidade Federal de Santa Catarina, Florianópolis, Brazil, 6Rua Astolfo Vieira de Resende, Faculdade de Medicina - UFMG, Belo Horizonte, Brazil, 7Disciplina de reumatologia, Universidade Federal de São Paulo, Sao Paulo, Brazil, 8Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil, 9Rheumatology, University Hospital, Faculty of Medicine, University of Brasília, Brasília/DF, Brazil, 10Hospital Universitário de Brasília - UnB, Brasília, Brazil, 11Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil, 12Internal Medicine, Hospital das Clínicas - UFPE, Recife, Brazil, 13Universidade de Cuiabá, Cuiabá, Brazil, 14Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 15Faculdade de Medicina - UFRGS, Porto Alegre, Brazil, 16Disciplina de Reumatologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 17Universidade Federal de São Paulo, São Paulo, Brazil First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Willingness to pay (WTP) is a technique used for valuing health benefits and individual preferences. Brazil’s national public health system (Sistema Único de Saúde) grants the population access to costly and effective drugs for the management of rheumatoid arthritis (RA). The aim of this study was to establish WTP valuations for highly effective drug treatments in Brazilian RA patients. Methods: This cross-sectional multicenter study enrolled adult RA patients (ACR 1987 or ACR/EULAR 2010 criteria) from rheumatology outpatient clinics of the Brazilian public health system. Consecutive patients were asked to reveal the maximum monetary value they would be willing to pay, on a monthly basis, for a hypothetical new intravenous drug offering a 90% improvement in their general health, thus a highly effective drug. Two WTP elicitation tools were used: a payment scale and an open-ended format. Demographic, social and clinical data were gathered from each subject. Disease activity was estimated by DAS28 score and physical function was assessed by HAQ-DI. Descriptive statistics were calculated. Results: From April 2014 to May 2015, 688 patients (87% female) were assessed in eight Brazilian centers from all over the country. Mean disease duration was 12.7 (8.7) years; mean DAS28 = 3.5 (1.4); mean HAQ-DI = 1.23 (0.8). Subjects had a median of 6 (0 to 21) years of schooling and median household income of US$ 610.3 (0 to 7,909.9) per month. Median WTP values were US$ 22.9 (Q1=11.5; Q3=91.6) on payment scale, and US$ 38.2 (Q1=22.9; Q3=76.3) on open-ended format. On payment scale, 4.2% (28/665) of the respondents assigned zero values for WTP. Overall, 12.4% (83/688) of the subjects added commentaries expressing no willingness to pay at all, regardless of the value (if any) assigned to the elicitation tools. The ratio between median WTP value (open-ended format) and median household income was 6.3%. Conclusion: This study set WTP valuations of highly effective intravenous drug treatments for chronic, moderately active RA, in outpatient clinics of the Brazilian public health system. The typical population attending to those clinics had low educational and income profile, and had free access to health resources, including medicines, seldom expecting to pay directly for their treatment. The stated WTP values were low, in face of the well known high costs of treating RA patients. Nonetheless, as a proportion of household income, WTP values were in line with the average expenditure of Brazilian families with health resources. Disclosure: C. Albuquerque, None; P. Haddad, None; V. Fernandes, None; C. Marques, None; S. Fialho, None; A. Kakehasi, None; F. Jennings, None; C. Brenol, None; L. M. H. Mota, None; G. Castelar-Pinheiro, Abbvie,
5,AstraZeneca, 5,GlaxoSmithKline, 5,Hospira, 5,Janssen Pharmaceutica Product, L.P., 5,Pfizer Inc, 5,RuiYi, 5,SanofiAventis Pharmaceutical, 5; A. Duarte, None; I. Giroto, None; M. R. C. Pinto, None; M. Toni, None; M. Mendes Abreu, None; M. B. Ferraz, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/willingness-to-pay-for-highlyeffective-drug-treatments-in-brazilian-rheumatoid-arthritis-patients
Abstract Number: 138
Identification and Documentation of Secondary Osteoarthritis in Patients with Primary Inflammatory Arthritides Using a Patient MDHAQ/RAPID3 and a Physician Estimate of Joint Damage to Recognize Patient Complexity and Inform Management Decisions Kathryn A. Gibson1, Annie Huang2, Katherine J. Bryant3 and Theodore Pincus2, 1Liverpool Hospital, Liverpool, Australia, 2Rheumatology, Rush University Medical Center, Chicago, IL, 3University of New South Wales, Sydney, Australia First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Patients with inflammatory arthritides may have secondary osteoarthritis (OA), which affects decisions concerning clinical management. For example, in one study, about 20% of patients with DAS28 scores >3.2, suggesting that therapy should be intensified according to treat-to-target, did not have intensification because of clinically important joint damage (1). We analyzed patient MDHAQ/RAPID3 scores and physician RheuMetric checklist estimates of damage (as well as overall global estimate, inflammation and distress) to identify and document secondary OA in patients with inflammatory arthritides seen in a busy clinical setting. Methods: All patients seen at one rheumatology site complete a MDHAQ/RAPID3, and the rheumatologists complete a RheuMetric physician checklist. The MDHAQ includes scores for physical function (0-10), pain (0-10), and patient global estimate (PATGL) (0-10), compiled into a RAPID3 (0-30) score. The 1-page physician RheuMetric checklist includes a standard 0-10 visual analog scale (VAS) for physician global estimate (DOCGL), and 3 further 0-10 VAS for the levels of inflammation or reversible findings (DOCINF), damage or irreversible findings (DOCDAM), and patient distress (e.g. fibromyalgia, depression) (DOCDIS), as well as primary, secondary and tertiary rheumatic diagnoses. Patients with RA, ankylosing spondylitis, psoriatic arthritis, and inflammatory arthritis were classified as “inflammatory arthritides”, and were further classified as having or not having comorbid secondary OA. Mean MDHAQ scores and RheuMetric estimates were computed in the two groups; statistical significance was analyzed using 2-tailed t-tests with significance at p3 ICD-9 codes of 710.0, >30 days apart). We required 6 months of continuous Medicaid enrollment (baseline period) prior to the 3rdcode (index date). Baseline data included age, year, sex, race/ethnicity, US region of residence. Subjects were followed from index date until death, Medicaid disenrollment or end of follow-up (12/31/2010). Within claims, CPT codes identified lipid testing and NDC codes identified statin prescription filling. We calculated rates per 1000 person-years for lipid testing and statin prescription filling, and rate ratios (with 95% CIs) to compare rates between sociodemographic groups. We tested for trends in lipid testing and statin prescription rates over time using Cochrane Armitage tests. Results: Of 37,999 patients with prevalent SLE, 93% were female. Mean age was 41.2 (+ 12.1) years. Race/ethnicity were: 42% Black, 36% White, 16% Hispanic, 2% Native American. Mean follow-up was 19.4 (+ 12.7) months; 746 patients died. In the entire cohort, 11,969 patients (32%) had >1 lipid testing and 6885 (18%) had >1 filled statin prescription. Lipid testing did not differ by sex, but statin prescription was slightly more frequent among men than women. The highest rates of lipid testing were seen among Hispanic and Asian patients (vs. White), older patients (ages 55-65 vs. younger), those living in the West (vs. other regions), and those receiving corticosteroids (vs. not). (Table) The highest rates for filled statin prescriptions were observed in older patients (ages 55-65 vs. younger), and those receiving corticosteroids. Black and Native American patients had lower rates of both lipid testing and statin prescription (vs. White patients). No geographic variation in statin prescribing was seen. Rates of both lipid testing (from 235.1 [227.3, 243.2] to 474.6 [450.9, 499.5] per 1000 person-years, p trend 1 statin prescription between 2007-10. Rates of both lipid testing and statin prescription increased significantly during this time. Rates were higher among older patients and those on corticosteroids. Given high CVD and mortality risks among Black and Native American SLE patients, it is noteworthy that these groups had low rates of lipid testing and statin prescriptions. Table. Rate Ratios for Lipid Testing and Statin Prescription Filling among Medicaid patients with SLE in the U.S., 2007-2010 Lipid Testing* Statin Prescriptions** Patient Group Rate Ratio 95% CI Rate Ratio 95% CI Female Ref. Ref. Ref. Ref.
Female Ref. Ref. Ref. Ref. Male 0.92 0.85-1.01 1.27 1.15-1.41 White Ref. Ref. Ref. Ref. Black 0.97 0.92-1.02 0.85 0.80-0.91 Race/Ethnicity Hispanic 1.35 1.27-1.43 1.01 0.92-1.10 Asian 1.63 1.45-1.83 1.17 0.99-1.38 Native 0.78 0.61-0.98 0.70 0.50-0.97 18-34 0.64 0.60-0.68 0.22 0.20-0.24 Age 35-44 0.81 0.76-0.86 0.42 0.39-0.46 45-54 0.93 0.87-0.98 0.73 0.68-0.79 55-65 Ref. Ref. Ref. Ref. West Ref. Ref. Ref. Ref. Northeast 0.77 0.73-0.82 0.99 0.90-1.08 US Region South 0.77 0.73-0.82 0.96 0.89-1.04 Midwest 0.65 0.61-0.69 1.09 0.99-1.19 Yes Ref. Ref. Ref. Ref. Receiving Corticosteroids No 0.41 0.39-0.43 0.42 0.39-0.45 2007 0.50 0.46-0.53 0.29 0.26-0.31 Calendar year 2010 Ref. Ref. Reference Reference *CPT codes for lipid screening (80061, 82465, 83700, 83701, 83715, 83716, 83721, 84478, 83718 (Morrato EH, Arch Pediatr Adolesc Med, 2010). Sex
**NDC codes used to identify statin use (Bateman BT, BMJ, 2015). Disclosure: S. Chen, None; M. A. Fischer, Alosa Foundation, 5,CVS-Caremark, Otsuka America, 9; H. Guan, None; M. Barbhaiya, None; K. H. Costenbader, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rates-of-lipid-testing-and-statinprescription-filling-among-u-s-medicaid-recipients-with-sle-2007-2010
Abstract Number: 147
Fatigue, Coping, Sleeping Disorders and Productivity Were Still Not Frequently Reported in Rheumatoid Arthritis Trials Published in 20142015: A Systematic Literature Review Levent Kilic1, Abdulsamet Erden1, Laure Gossec2 and Umut Kalyoncu1, 1Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, 2Rheumatology, Pitié Salpetriere Hospital, Paris, France First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: In a systematic literature review (SLR), frequency of patients reported outcomes (PROs) related with rheumatoid arthritis (RA) was evaluated between 2005 and 2007 (1). Relatively low frequent outcome measures at this SLR were fatigue, utility, psychological status, coping, sleeping disturbance, productivity losses, wellbeing and leisure. Although pain and function are essential domains for patients, priority of patients also include fatigue,
emotional well-being, sleep, coping and physical well-being (2). Objective of this study was to assess frequency and changing trend of PROs related with RA at the last 2 years. Methods: Literature search was performed in PUBMED MEDLINE database on 01 January 2015. Publications were identified through a search that used the following exploded MeSH term: (‘‘arthritis, rheumatoid’’ (MeSH)) with a limitation to ‘‘humans’’, ‘‘all adults: 19+ years’’, ‘‘English’’, ‘‘published in the last 2 years’’ and ‘‘clinical trials’’. Publications were limited to articles referenced in PUBMED in the last 2 years. Demographic characteristics of patients, study design, treatments assessed and all PROs assessed. Results were compared with previous SLR (1). Results:Of the 479 publications identified by the literature search, 250 were included in the analysis. Of the 250 publications, 113 (45.2%) were randomized controlled trials. One hundred-forty different tools were reported in this SLR. Function (83.4% vs 68.0%), pain (55.9% vs 40.0%), patient global assessment (63.3% vs 49.2%) and quality of life (19.2% vs 18.4%) were still essential PROs. Frequency of fatigue (13.7 vs 14.4), psychological status (7.3 vs 9.6), productivity losses (5.5 vs 6.4) and sleeping disturbance (1.8 vs 2.4) were not changed over time. On the other hand, frequency of morning stiffness (26.6 vs 10.0), coping (6.4% vs 2.0%) and utility (16.5 vs 5.2) were decreased. Although fatigue assessed with valid tools (VAS 7.2%, FACIT 4.8%), other less frequent domains (psychological status, productivity losses, sleeping disturbance, coping) did not have constant and specific tools for RA. Conclusion: Eight years later, we still did not determine any significant change about PROs in RA trials. Priority of patients, for instance fatigue, psychological status, productivity losses, sleeping disturbance, coping were not sufficiently appear RA trials. One of the major challenge of those PROs was also related with tools. Tools about psychological status, productivity losses, sleeping disturbance and coping had high heterogeneity and low specificity for RA. Ref: 1. Kalyoncu U, Dougados M, Daurès JP, Gossec L. Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: a systematic literature. Ann Rheum Dis. 2009;68:183-90. 2. Gossec L, Dougados M, Rincheval N et al. Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative. Ann Rheum Dis. 2009;68:1680-5. Disclosure: L. Kilic, None; A. Erden, None; L. Gossec, None; U. Kalyoncu, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/fatigue-coping-sleeping-disordersand-productivity-were-still-not-frequently-reported-in-rheumatoid-arthritis-trials-published-in-2014-2015-asystematic-literature-review
Abstract Number: 148
An Evaluation of the Virtual Monitoring Clinic, a Novel Nurse-Led Telemonitoring Service for Monitoring Patients with Stable Rheumatoid Arthritis Li-Ching Chew1, Julian Thumboo1, Hui Yang2 and Xiaohui Xin3, 1Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore, 2Division of Medicine, Singapore General Hospital, Singapore, Singapore, 3Academic Clinical Programme, Division of Medicine, Singapore General Hospital, Singapore, Singapore First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Health Services Research Poster I: Diagnosis, Management and Treatment Strategies
Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: To study the clinical and patient reported outcomes of the Virtual Monitoring Clinic (VMC), which is novel nurse-led telemonitoring cum pharmacy medication home delivery service for monitoring stable Rheumatoid Arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). Methods: Patients with stable RA enrolled into the VMC programme were followed up prospectively. The primary outcomes evaluated at 1-year were: Disease Activity Score-28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), and patient satisfaction score assessed using an 11-point Likert scale. Results: Of the 251 patients enrolled, 186 completed 1year of follow-up. 2.3% of the annual workload from the specialist outpatient clinic was freed up as a result of the VMC programme. Statistically significant improvement was seen in the mean satisfaction score (7.70 to 8.16, p1 and/or PD>0. Simple descriptive statistics were used and longitudinal course of DAS28 and number of ultrasound positive MTP joints were plotted for each patient. Results: At baseline, 174 patients were included of whom 159 completed one year follow-up. At baseline, 109 (73%) patients had at least one ultrasound positive MTP joint. Overall, mean(sd) DAS28 decreased from 4.9(1.3) at baseline to 2.3(1.2) at one year, while the number of ultrasound positive MTP joints decreased from median(interquartile range) 1(0-4) at baseline to 0(0-0) at one year. Discordance in evolution of DAS28 and ultrasound positive MTP joints over one year was seen in 9 patients (6%). After one year of follow-up, 98 (62%) patients were in DAS28 remission (DAS28 0, % 73 43 25 US = ultrasound; LDA = low disease activity; sd = standard deviation; IQR = interquartile range
Disclosure: M. van der Ven, None; D. F. Ten Cate, None; A. Gerards, None; J. Jacobs, None; N. Swen, None; M. H. de Jager, None; N. Basoski, None; C. Haagsma, None; M. Hazes, None; J. J. Luime, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ultrasonographic-signs-ofinflammation-of-metatarsophalangeal-joints-in-rheumatoid-arthritis-patients-who-are-treated-to-target
Abstract Number: 170
Relationship Between Finger Joint Cartilage Evaluated By Ultrasound and Clinical Characteristics in Rheumatoid Arthritis (RA) Takehisa Ogura1, Ayako Hirata1, Hideki Ito2, Sayaka Takenaka2, Kennosuke Mizushina1, Yuki Fujisawa1, Naoko Yamashita1, Munetugu Imamura2, Norihide Hayashi2 and Hideto Kameda1, 1Department of Rheumatology, Toho University Ohashi Medical Center, Tokyo, Japan, 2Toho University Ohashi Medical Center, Tokyo, Japan First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Imaging of Rheumatic Diseases Poster I: Ultrasound, Optical Imaging and Capillaroscopy Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Joint destruction is the primary lesion by bone and cartilage damage in RA. By X-ray examination, cartilage destruction is evaluated as a joint space narrowing, although it is not the direct evaluation of cartilage itself. The aim of the study was to clarify the relationship between the finger joint cartilage evaluated by ultrasound (US) imaging and clinical characteristics in RA. Methods: We examined 29 RA patients in clinical remission (DAS28-CRP < 2.6). The cartilage layer of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints for 2nd to 5th fingers was bilaterally visualized from a dorsal view, with joints in approximately 90 degrees flexion. Cartilage thickness (CT) was measured with
integrated tools on static images, and thickness was compared with other clinical and laboratory parameters. Results: CT in MCP joints ranged from 0.0 to 0.8 mm (average 0.4 mm), and CT in PIP ranged from 0.0 to 0.5mm (average 0.2mm), respectively. The sum of total CT from 8 fingers ranged from 2.7 to 6.8 mm (average 4.8 mm). CT measured by ultrasound was not correlated with age, DAS28-CRP, functional disability score, positivity of rheumatoid factor and anti-CCP-antibody. However, there was significant relationship between CT and disease duration (r=-0.438, p=0.017). Moreover, CT was reduced in RA patients with elevated serum matrix metalloproteinase-3 (MMP-3) values compared with those with normal MMP-3 values (4.2 versus 5.0, p=0,046). Conclusion: The US method of direct visualization and quantification of cartilage in MCP and PIP joints can be valid and useful in RA, and our results supported the importance of MMP-3 in the pathophysiology of cartilage destruction. Disclosure: T. Ogura, None; A. Hirata, None; H. Ito, None; S. Takenaka, None; K. Mizushina, None; Y. Fujisawa, None; N. Yamashita, None; M. Imamura, None; N. Hayashi, None; H. Kameda, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-between-finger-jointcartilage-evaluated-by-ultrasound-and-clinical-characteristics-in-rheumatoid-arthritis-ra
Abstract Number: 171
Serum Calprotectin Levels Correlate with Ultrasonographic Synovitis in Rheumatoid Arthritis Patients Jana Hurnakova1, Jakub Zavada1, Petra Hanova1, Hana Hulejová1, Martin Klein1, Herman F Mann1, Olga Sleglova1, Marta Olejarova1, Šárka Forejtová1, Olga Ruzickova1, Martin Komarc2, Jiri Vencovsky1, Karel Pavelka1 and Ladislav Senolt1, 1Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic, 2Institute of Biophysics and Informatics of the First Faculty of Medicine, Charles University, Prague, Czech Republic First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Imaging of Rheumatic Diseases Poster I: Ultrasound, Optical Imaging and Capillaroscopy Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Calprotectin (S100A8/9, MRP8/14) has been demonstrated as a promising biomarker of clinical and laboratory disease activity in rheumatoid arthritis (RA). In addition, two small previous studies have shown that calprotectin might by associated with ultrasound-determined synovitis 1,2. The aim was to evaluate associations between calprotectin and conventional disease markers as well as ultrasound parameters of disease activity in a larger cohort of RA patients. Methods: A total of 160 patients with RA (128 females, median disease duration 4.8 years) were recruited in this study. All patients underwent clinical (DAS28, CDAI, SDAI) and ultrasound examination (German US-7 score) 3. The levels of serum calprotectin and CRP were measured at the time of ultrasound assessment. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Multiple regression analysis was used to determine the predictive value of calprotectin, CRP and DAS28 to determine GS and PD synovitis scores.
Results: We found that calprotectin was significantly associated with DAS28 (r=0.332, p85% and soft tissue 63%. Attitudes: More than 60% of the Rs report that MSK US results often lead to a change in their management plans and that it enhances patients’ satisfaction. 82% think it appropriate that RC should perform MSK US scans as part of their RWP. 50% of the RC and 72% of the RT think that proficiency in use of US should be a mandatory part of the rheumatology training curriculum. 51% of the Rs indicated a willingness to learn the technique. Free text responses revealed concerns about available time and proper training but others commented that MSK US is beneficial in an early IA setting. Conclusion: This cross-sectional, observational, multicentre survey demonstrates widespread use of MSK US by rheumatologists in routine care in the South East Coast region of England. 82% of Rs think it appropriate that RC should perform MSK US in RWP and 57% believe training in this should be a mandatory part of the curriculum. In contrast 42% of Rs have had formal training, but only 10% of them have incorporated MSK US into RWP, the majority relying on radiology colleagues to do the scans. This illustrates a discrepancy between attitudes, desire and reality of MSK US use in routine rheumatological practice. Disclosure: A. Grigoriou, None; P. Kiely, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/rheumatologists-andmusculoskeletal-ultrasound-discrepancy-between-attitudes-desire-and-reality-in-routine-practice-in-south-east-england
Abstract Number: 185
Success Rate and Utility of Ultrasound Guided Synovial Biopsies in Clinical Practice Aurélie Najm, Benoît Le Goff and Yves Maugars, Rheumatology, Rheumatology, Nantes, France First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Imaging of Rheumatic Diseases Poster I: Ultrasound, Optical Imaging and Capillaroscopy Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Histological and bacteriological analysis of synovial tissue (ST) can be useful in the diagnosis of arthritis of undetermined origin. Ultrasound can assist this biopsy in directing the needle to relevant sites within the joint as well as allowing an evaluation of synovial inflammation and thickness. The aims of this study were to describe the indications for US guided synovial biopsies in clinical practice, to determine the rate of success in acquiring ST using this approach and to determine how frequently the synovial biopsy can lead to a definite diagnosis. Methods: Synovial biopsies of small and large joints were performed under US guidance (Philips HD11 XE) between January 2007 and December 2014 using a semi-automatic core biopsy needle (Tru-cutR). The patient cohort was characterized clinically. Crystal microscopy, bacteriological (with PCR for Whipple or Lyme disease), mycobacteriological and fungal analysis were performed according to the clinical presentation. Histological features of biopsies were described. The biopsy procedure was considered as successful if synovial tissue was found at histological examination. Results: Seventy-two patients underwent 74 synovial biopsies. Fifty-three percent were men and average age was 58,7 years (+/- 16,97). Biopsies were performed in the following joints: knee (n=42; 56%), ankle (n=7; 10%), wrist (n=7; 10%), shoulder (n=6; 8%), hip (n=4), sterno-clavicular (n=3), elbow (n=3), pubic symphysis (n=1), acromio-clavicular (n=1), first metatarsophalangeal (n=1). Patients presented with a chronic (> 3 months) monoarthritis in 42 cases (56%), an acute monoarthritis in 17 cases (23%), a chronic polyarthritis in 13 cases (18%), an acute polyarthritis, a chronic tenosynovitis and a chronic bursitis in 1 case respectively. Biopsies were performed to rule out the diagnosis of septic arthritis in 64 cases (85%) or of villonodular synovitis in 11 cases (15%). US guided biopsy attempt succeeded in 85% of cases (63 on 74 biopsies performed). Failed biopsies retrieved fibrin deposition or adipose tissue.There was no difference on success rate between small and large joints. Ten of the 63 biopsies (17,5% of patients) leaded to a definitive diagnosis: 2 septic arthritis (no bacteria found on cultures, but a typical histological aspect), 2 villonodular synovitis, 1 case of amyloid arthritis on a patient having no known myeloma, 1 joint localization of a mantle cell lymphoma, 1 gouty arthritis, 1 osteochondromatosis, 1 Whipple disease (positive PCR on synovial tissue, with negative PCR on synovial fluid) and 1 Lyme arthritis (positive PCR on synovial tissue). The histological analysis of the 54 other biopsies showed a non-specific cell infiltrate with lymphocytes and/or macrophages. One patient presented a knee hemarthrosis 48 hours after the US guided biopsy.
Conclusion: Ultrasound guided synovial biopsies in clinical practice are performed on patients with heterogeneous features. The rate of success in acquiring synovial tissue is high. The procedure, when successful, leads to a definite diagnosis in more than 1 on 6 patients with an arthritis of undetermined origin. Disclosure: A. Najm, None; B. Le Goff, None; Y. Maugars, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/success-rate-and-utility-ofultrasound-guided-synovial-biopsies-in-clinical-practice
Abstract Number: 186
B Flow, a Novel Ultrasound Modality in the Assessment of Synovitis in RA Darren Tabechian1, Laura C Coates2, Jennifer H. Anolik1 and Ralf G. Thiele1, 1University of Rochester Medical Center, Rochester, NY, 2LIMM, Section of Musculoskeletal Disease, University of Leeds, Leeds, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Imaging of Rheumatic Diseases Poster I: Ultrasound, Optical Imaging and Capillaroscopy Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: B flow is a vascular ultrasound (US) technique in which the high resolution aspect of gray scale US is optimized to demonstrate movement of one tissue (particularly of erythrocytes) against the background of stationary structures. Though power Doppler can demonstrate relatively low flow structures such as synovial vessels and the neovascularization characteristic of active synovitis, it is in part a flow-direction dependent technique. B flow has been shown to demonstrate carotid artery stenosis as well as color Doppler techniques while more accurately depicting background non-vascular anatomy 1. The goal of this study is to evaluate the utility of B flow in the assessment of inflammatory arthritis. Methods: In a cohort of 10 patients with CCP positive RA (fulfilling the 2010 EULAR/ACR classification criteria) with at least one swollen joint, 120 joints (wrists and MCP joints) were assessed by gray scale US. 51 of the 120 joints were determined to have grade 1 or greater synovitis and underwent power Doppler and B flow interrogation. Two sonographers independently scanned all patients with a GE logic E9 and a 15Mhz matrix array transducer for PD imaging. B flow was performed with an 18 MHz transducer with settings for venous flow. Image scoring for both PD and b flow was performed by the same 2 rheumatologist sonographers (DT and RT) using a reference scoring atlas 2 Results: 51 joints were assessed by PD and B flow. There was a good to very good agreement between B flow and PD scores (quadratic weighted kappa 0.62 and prevalence-adjusted and bias-adjusted kappa (PABAK) using quadratic weights k= 0.86, p 25% green regions and > 10% but < 25% blue regions, grade 3 demonstrates 25-50% green region and > 25% but 50% blue regions (“hard tissue”); this grading 1-4 was labelled the elastography score (ES). Statistical analysis of response was performed with ShapiroWilk test and student t-test. Results: The normal hand had an average ES of 5.08 in the UpS and an ES of 16 in the LwS. In contrast, the untreated Dupuytren’s hand had an average ES of 12.36 in the UpS and an ES of 15.6 in the lower segment. The normal hand ES UpS vs untreated Dupuytren’s hand UpS had p < 0.01 but the normal hand ES LwS and untreated Dupuytren’s hand ES LwS did not. In the treated Dupuytren’s hands, the ES UpS at baseline 11.6 decreased to 9.1 in the first 24 hours of treatment and by day 30 was 8.8 and the ES LwS changed from 14.4 to 12.7; the contracture changed from 35.6o to 23o and the URAM scale changed an average of 2 points. The normal hand ES UpS vs treated ES UpS had p < 0.01. Conclusion: This pilot established an elastographic regional scoring system for normal and pathologic tissue affected by a fibrotic disorder and demonstrated that the elastographic regional scoring system could detect response to treatment. This has significant clinical implications for the treatment of Dupuytren’s contracture as well as for other rheumatologic fibrotic disorders. Further study with a larger cohort is needed. Disclosure: P. J. DeMarco, Auxilium Pharmaceuticals, 2,Amgen, 8,Abbott Immunology Pharmaceuticals, 8,AstraZeneca, 2; A. K. Matsumoto, None; N. Thomas, None; M. Bishop, None; A. G. DeMarco, None; G. Respicio, None; A. Beall, None; R. Rosenberg, None; T. Bass-Goldman, None; H. S. B. Baraf, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/ultrasound-imaging-withelastography-for-the-medical-treatment-of-dupuytrens-contracture
Abstract Number: 191
High Specificity of Spectral Nail Assessment in Psoriatic Arthritis Patients JOSE ALEXANDRE MENDONÇA, 4Rheumatology Unit, Hospital da Pontifícia Universidade Católica (PUC) de Campinas, Campinas, Brazil, Porto Alegre, Brazil; Rheumatology, Instituto de Pesquisa Clínica of Campinas – IPECC, Campinas, Brazil First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Imaging of Rheumatic Diseases Poster I: Ultrasound, Optical Imaging and Capillaroscopy Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM
Background/Purpose: Ultrasound evaluation of synovitis and enthesitis has changed the management of rheumatic diseases. In the present study we compare Power Doppler (PD) and Spectral Doppler (sD) ultrasonography indices (semiquantitative gray scale and PD scores and resistance index (RI) in the nails of patients with psoriatic arthritis (PsA) and their controls. Potential associations between sD measurements and clinical parameters were also investigated1,2,3. Methods: A cross sectional study was done and 44 patients with PsA, if they fulfilled the CASPAR criteria, 10 healthy controls and 6 patients with hands osteoarthritis (OA) were enrolled. Clinical parameters were recorded while US evaluation was performed in patients and controls nails. Nail bed measurements and semiquantitative gray scale (GS) and PD scores were derived for all nails examined, while RI was measured using sD. Results: Statistically significant lower RI was found in patients with PsA as compared to their controls (p1Tophus PD>0 PD>1 deposit 1st MTP
Multiple regression analysis showed that the presence of synovitis >0 was only statistically associated in the 1st MTP to tophi (R2 0.31), and in the knee to the presence of extense or bilateral DCS and tophi (R2 0.28). The PD>0 signal was only associated in both 1st MTP and in knee to tophi (R2 0.25 and 0.18, respectively). The more restrictive analysis of synovitis>1 and PD>1 did not show changes in the results, although numbers were small. Conclusion: ultrasonographic urate deposits, as tophi or extense double contour) are associated to synovitis or active synovitis (intra-articular synovitis with PD signal) as markers of synovial inflammation. The presence of tophi is the main factor associated, so the resolution of the intra-articular tophi seems to be the principal therapeutic goal for uratelowering therapy. Disclosure: F. Perez-Ruiz, AstraZeneca, 5,AstraZeneca, 8,Menarini, 5,Menarini, 8; S. P. Chinchilla-Gallo, None; I. Urionagüena, None; E. Garmendia, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-betweenultrasonographic-synovial-inflammation-and-ultrasonographic-urate-deposition-findings-in-patients-with-gout
Abstract Number: 239
The Role of Dual Energy Computed Tomography in Diagnosing Acute Gouty Arthritis: Comparison with Ultrasound and Aspiration Jennifer Lee 1, Ji Yeon Lee2, Jung Hee Koh3, Min Kyung Chung4, Ji Hun Kim1, Seung-Ki Kwok5, Ji Hyeon Ju6 and Sung-Hwan Park7, 1Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea, 2Division of Rheumatology, Department of Internal Medicine, School of Medicine, Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, South Korea, 3Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea, 4Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, South Korea, 5Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea, 6Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, 7Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea First publication: September 29, 2015
SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: The gold standard of acute gouty arthritis diagnosis has been to verify the presence of monosodium urate (MSU) crystal in the aspirated fluid of the affected joint. Recently, dual energy computed tomography (DECT) has emerged as a non-invasive MSU detecting tool. This study was undertaken to evaluate the diagnostic accuracy of DECT in acute gouty arthritis and to determine the affecting factors. Methods: Medical charts of patients who underwent both DECT and ultrasound (US) guided aspiration in suspicion of acute gouty arthritis from August 2013 to March 2015 were retrospectively reviewed. Positive ultrasound findings included effusion with snowstorm appearing microtophi or double contour sign or presence of tophi. For statistical analysis, Mann-Whitney U test was used for continuous variables. Chi-Square test was used for categorical variables. Results: A total of 74 patients were analyzed. All patients except one were male and mean age was 45.3 years. Mean disease duration was 46 months, mean serum uric acid level 7.4 mg/dL. Fifty six patients had one or more positive findings of DECT or US or MSU presence in aspirated joint fluid. MSU deposition was observed in 28/61 (46.0%) patients. There were 4 patients who had clinically apparent tophi on physical examination, all of which were detected on DECT. Joint fluid was successfully acquired in 40/61 (65.5%) patients and the presence of MSU crystal was confirmed in 28 patients. Positive US findings were observed in 60/61 (98.4%) patients. 26 patients showed positive findings of both DECT and ultrasound, whereas 34 patients had only positive ultrasound findings. Serum uric acid level, symptom duration was significantly greater in DECT(+) positive group. Of note, DECT could not detect MSU crystal in patientswith high BMI. After adjusting age, multivariate logistic regression revealed that DECT may not be appropriate in patients with high BMI and short symptom duration in acute setting. Conclusion: DECT can detect MSU deposition in acute gout patients without clinical tophi. However, the probability of false negativity rises in patients with high BMI and short symptom duration. Disclosure: J. Lee, None; J. Y. Lee, None; J. H. Koh, None; M. K. Chung, None; J. H. Kim, None; S. K. Kwok, None; J. H. Ju, None; S. H. Park, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-role-of-dual-energy-computedtomography-in-diagnosing-acute-gouty-arthritis-comparison-with-ultrasound-and-aspiration
Abstract Number: 240
Volumetric Assessment of Tophaceous Gout Ralf G. Thiele 1, Laura Coates2 and Darren Tabechian1, 1University of Rochester Medical Center, Rochester, NY, 2Medicine, University of Rochester, Rochester, NY First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM Background/Purpose: Ultrasound (US) can identify monosodium urate (MSU) tophi within joints, tendons, bursae and other soft tissues. The ability to readily, quickly and inexpensively assess volumes of tophi would be an attractive goal. Available 3D ultrasound transducers can scan tophi, and volumes can be re-constructed using commercially available software. The aim of this study was to assess the feasibility, repeatability and reproducibility of US volumetric assessment of MSU tophi. Methods: 14 consecutive patients (9 male, 5 female, 32-84 years) with a history of gout and previously US identified MSU tophi were enrolled. Eleven were on urate lowering drugs (allopurinol, n=7; febuxostat, n=2; pegloticase, n=1). Joint areas included MTP1 n=8, Achilles tendon, n=1; MCP2, n=1, olecranon, n=1; prepatellar, n=1; wrist, n=1. Only 2 had clinically palpable tophi (prepatellar and olecranon bursae). Medial fullness at MTP 1 was palpable in 4, but could not be distinguished by clinical exam from hallux valgus. A GE Logiq E9 built 2014 unit with a RSP6-16-D 4D linear transducer at 15 MHz was used. After placement the probe performed an internal sweep of 3 seconds to obtain the 3D data set. Volumetric analysis was performed using volume calculation software (VOCAL, GE Ultrasound, Wauwatosa, WI.) Tophi were identified as typical hyperechoic material with an anechoic rim, if present. The 3D image was rotated 6 times at 30 degree intervals. The area of the tophus on each orientation was traced manually on the screen. The software provided the volume of the resulting structure in cm3. For each resulting tophus volume, this process was performed twice by the first reader (RT) to test the intra-observer reliability. For 6 tophi, an additional volume calculation was performed by a second rheumatologist-sonographer to test the inter-observer reliability. Results: The software-aided volume analysis took on average 6 minutes per assessment. Reader 1 (RT) calculated a mean volume of 0.682cm3 (standard deviation (SD) 0.699, range 0.03 to 2.60) in the first reading and 0.705cm3 (SD 0.705, range 0.03 to 2.60) in the second reading. ICC showed excellent intra-reader reliability for reader 1 (0.995, 95% CI 0.985, 0.998). Reader 2 (DT) scored 6 of the 14 scans and calculated a mean volume of 0.607cm3 (SD 0.595, range 0.05 to 1.40). The ICC showed excellent inter-reader reliability between reader 1 and reader 2 (ICC 0.990, 95% CI 0.928, 0.999 using reader 1's first reading and ICC 0.994, 95% CI 0.958, 0.999 – second reading).
Conclusion: Volumetric assessment of MSU tophi by reconstruction of 3D ultrasound is a feasible, fast, inexpensive method to assess the tophus burden with excellent intra- and inter-reader reliability in this study. Future work should evaluate sensitivity to change and with positive results this method could act as an objective outcome measure for clinical trials of urate lowering therapy. Disclosure: R. G. Thiele, None; L. Coates, None; D. Tabechian, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/volumetric-assessment-of-
Abstract Number: 241
Inflammatory Syndrome in Polyarticular Gout – Description of a Previously Neglected Entity Valentin S. Schäfer1, Andreas Krause2 and Wolfgang A. Schmidt2, 1Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch, Berlin, Germany, 2Medical Center for Rheumatology and Clinical Immunology BerlinBuch, Immanuel Krankenhaus Berlin, Berlin, Germany First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Inflammatory polyarticular gout occurs in clinical practice. However, only very few single case reports have been published as yet. This case series aims at describing this previously poorly defined entity. Methods: This is a retrospective analysis of all consecutive patients of a single rheumatology center between January 2013 and April 2015. Patients were included with polyarticular gout with at least 5 joint regions involved (1st MTP joints, other MTP joints, ankles, knees, wrists, digits, elbows) and highly elevated inflammatory markers (CRP >80 mg/l and/or ESR > 80mm/h). Joint involvement was considered if clinical examination revealed swelling or tophi, or if imaging (ultrasound, dual energy CT or x-ray) showed features consistent with gout. Demographic, laboratory, imaging, clinical parameters and treatment regimens were recorded. Results: Of the 22 included patients, 18 were male; mean age 67 years (standard deviation (SD), ±11 years); mean BMI 29 (SD ±6). The diagnosis was confirmed in 19 patients by polarization microscopy. All patients fulfilled the new ACR/EULAR classification criteria for gout. Fourteen (64%) patients were newly diagnosed with gout. The other patients had been diagnosed with gout for a mean of 10 years (SD ±10). All patients except one were admitted to hospital due to the inflammatory syndrome. The median duration of the acute symptoms before presentation to our institution was 13 days (minimal / maximal, 2-90). A mean of 10 joint regions (minimal / maximal, 5-14) were affected. Of note, only 3 patients (14%) had fever (37.8, 38.1, 39°C, respectively). Mean visual analogue scale (VAS) for pain, disease activity and fatigue was 8.3, 8.1, and 6.7. The mean CRP was 172 mg/l (SD ±83.6 mg/l); mean ESR, 91 mm/h (SD ±24 mm/h). All patients had anemia (mean hemoglobin, 7.2 mmol/l; SD± 0.9mmol/l). Leukocytosis was found in only 6 patients (27%; mean, 14.8 G/l), thrombocytosis in 7 patients (32%; mean 405 G/l) and neutrophilia in 12 patients (54%; mean, 9.9 Gpt/l). In 12 (55%) of patients serum ferritin was elevated (mean 391 µg/l). Procalcitonin was normal in all 11 patients in whom it had been determined. Mean uric acid levels were 531 µmol/l (8.9 mg/dl). In 8 patients (36%) acute renal failure was observed, defined as >1.5 fold increase of creatinine. Ten patients had a glomerular filtration rate (GFR) of 30-60 ml/min; in 2 patients GFR was 80 mm/h are severely affected but rarely exhibit fever. Anemia is common. Leucocytosis and thrombocytosis are rare. Procalcitonin is usually normal. Renal failure occurs in Disclosure: V. S. Schäfer, None; A. Krause, Berlin Chemie, 8,Novartis Pharmaceutical Corporation, 5,Novartis Pharmaceutical Corporation, 8; W. A. Schmidt, Berlin-Chemie, 8,Berlin-Chemie, 5,Novartis Pharmaceutical Corporation, 8,Novartis Pharmaceutical Corporation, 5. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/inflammatory-syndrome-inpolyarticular-gout-description-of-a-previously-neglected-entity
Abstract Number: 242
Higher Serum Uric Acid Levels Are Associated with an Increased Risk of Flares: A Systematic Review Aki Shiozawa1, Shelagh M Szabo2, Antoinette Cheung2, Anna Bolzani2 and Hyon K. Choi3, 1Global Outcomes and Epidemiology Research, Takeda Pharmaceuticals International, Inc, Deerfield, IL, 2Redwood Outcomes, Vancouver, BC, Canada, 3Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Acutely painful flares represent the typical clinical burden of gout. Effective therapy can reduce serum uric acid (sUA) levels; however, epidemiologic evidence for the relationship between sUA and the risk gout flares is thought to be limited. The objective here was to systematically summarize the evidence of the association between sUA levels and the risk of gout flares. Methods: A systematic review of the published literature (1946 to present) was conducted in April 2015 in Medline, EMBASE, and Cochrane, using a search strategy including terms for gout, sUA, and flares. Two reviewers screened abstracts and extracted data from eligible articles reporting flares according to sUA level. The number and proportion of patients experiencing flares, or mean (standard deviation [SD] or error [SE]) flares per patient, were tabulated according to sUA category; mean sUA levels were also tabulated by mean gout flares. Studies were classified as retrospective (flares occurred prior to sUA measure) or prospective (flares occurred after sUA measure), and according to the treatment status of the cohort. Results: Of 866 abstracts, 19 articles presented estimates of flares according to sUA, and 17 presented estimates relevant to these analyses. In the seven studies describing flares according to sUA category, the proportion of the cohort experiencing flares increased in a dose-response fashion with higher sUA levels; as did the mean flares per gout patient (Table 1). The proportion experiencing flares was 1.4- to 2.8-fold higher in the highest sUA categories compared to the lowest. Mean flares also generally increased with higher sUA levels (Table 1). Ten studies also presented data on mean flares according to mean sUA level; these also demonstrated a dose-response relationship. As expected, clinical cohorts tended to show this relationship more clearly than administrative cohorts. Conclusion: Our systematic review of published articles on the risk of gout flares suggested a dose-response relationship, where higher sUA levels were associated with more flares. The selection, assessment methods, and timing
of outcome measures were variable between studies. As little evidence from prospective studies designed to comprehensively evaluate flares was identified, existing risk measures are likely underestimates. Nevertheless, the existing evidence underscores the need to treat to target as recommended by the recent gout care guidelines. Table 1: n (%) patients with flares, and mean (SD) flares over time, according to sUA level and the treatment status of the cohort
Disclosure: A. Shiozawa, Takeda Pharmaceuticals International, Inc., 3; S. M. Szabo, None; A. Cheung, None; A. Bolzani, None; H. K. Choi, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/higher-serum-uric-acid-levels-areassociated-with-an-increased-risk-of-flares-a-systematic-review
Abstract Number: 243
Increase in Risk of Future Attacks in Patients with Incident Gout: A Population-Based Study over 20 Years Nour Zleik1, Mohanad Elfishawi1, Zoran Kvrgic1, Clement J. Michet Jr.2, Cynthia S. Crowson3, Eric L. Matteson4 and Tim Bongartz1, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Mayo Clinic, Rochester, MN, 3Health Sciences Research, Mayo Clinic, Rochester, MN, 4Division of Rheumatology, Department of Internal Medicine and Department of Health Sciences Research, Mayo Clinic, Rochester, MN First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: While there appears to be consensus that non-pharmacological uric acid lowering therapies (diet and lifestyle modifications) should be initiated in every patient presenting with gout, there is much less agreement as to when urate lowering drugs should be considered. Expert opinion ranges from starting uric acid lowering therapy after the first attack of gouty arthritis through a more cautious approach where therapy is only started in patients with more than 3 attacks per year. We aimed to assemble a population-based cohort of patients with newly diagnosed gout
to determine the risk of additional flares after an initial gout attack and explore the role of various demographic, clinical and laboratory predictors that may aid the clinician in quantifying this risk. Methods: We examined a population-based incidence cohort of patients with gout, diagnosed according to the New York, Rome or ACR preliminary criteria during two time periods: January 1st 1989 - December 31st 1992 and January 1st 2009 – December 31st 2010. All subjects were followed longitudinally through their complete community medical records, until 5 years after their first gout attack, death, migration or July 1st 2012 – whichever came first. Person-year methods were used to estimate and compare flare rates over time. Frailty models (accounting for multiple flares per subject) were used to explore risk factors of subsequent flares. Results: 429 patients with incident gout (158 patients in the 1989-1992 time period and 271 patients in the 2009-2010 time period) were followed for a mean of 4.2 years. The majority of patients were male (73%) and the mean age (SD) at gout onset was 59.7 (17.3). Isolated podagra was the most common form of joint involvement at disease onset (64.0%) and the mean (SD) serum uric acid level was 8.1 (1.9) mg/dl. 248 patients developed at least 1 subsequent flare (cumulative incidence of first flare was 61.6% by 5 years in 1989-1992 vs 60.3% by 5 years in 2009-2010; p=0.70), with a total of 582 subsequent flares during the entire follow-up period. The rate of subsequent flares increased significantly from 2.82 per 10 person-years (py) in 1989-1992 to 3.49 per 10 py in 2009-2010 (rate ratio [RR]: 1.23; 95% confidence interval [CI]: 1.04, 1.47). Men were at higher risk for subsequent flares than women (HR 1.51, 95% CI 1.14, 2.00). Other predictors were a high serum uric acid level (>6mg/dL in women and >7mg/dL in men) at baseline (HR 2.20, 95% CI 1.49, 3.27), polyarticular involvement (HR 1.46, 95%CI 1.00, 2.13) and diuretic use (HR 1.30, 95%CI 1.03, 1.65). Age and body mass index were not significant predictors of subsequent flare risk. Conclusion: The majority of patients in our population-based cohort did develop at least one subsequent flare after an initial diagnosis of gout. The rate of subsequent flare was higher in patients diagnosed in 2009-2010 compared to those diagnosed in 1989-1992. Male sex, use of diuretics, polyarticular involvement and high uric acid levels at first flare were significant predictors of subsequent flares and should be taken into account when deciding on the timing of initiating uric acid lowering therapy. Disclosure: N. Zleik, None; M. Elfishawi, None; Z. Kvrgic, None; C. J. Michet Jr., None; C. S. Crowson, None; E. L. Matteson, None; T. Bongartz, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/increase-in-risk-of-future-attacksin-patients-with-incident-gout-a-population-based-study-over-20-years
Abstract Number: 244
Hospitalization and Flare Risk in Patients with Established Gout: A Population-Based Study Nour Zleik1, Mohanad Elfishawi1, Zoran Kvrgic1, Clement J. Michet Jr.2, Cynthia S. Crowson3, Eric L. Matteson4 and Tim Bongartz1, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Mayo Clinic, Rochester, MN, 3Health Sciences Research, Mayo Clinic, Rochester, MN, 4Division of Rheumatology, Department of Internal Medicine and Department of Health Sciences Research, Mayo Clinic, Rochester, MN First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015
Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Hospitalization of patients with gout may be associated with an increased risk of arthritic flares, due to administration of IV fluids, discontinuation of established uric acid lowering therapies and other medication changes. While previous studies have suggested an association of gouty arthritis and hospitalization, the absolute flare risk has not been identified. We aimed to determine the risk of flares with future hospitalizations and examine potential predictors of in-hospital gout flares. Methods: We examined a population-based incidence cohort of patients with gout, diagnosed according to the New York, Rome or ACR preliminary criteria during two time periods: 1989 - 1992 and 2009 – 2010. All subjects were followed longitudinally through their complete medical records, until 5 years after their first gout attack, death or migration, whichever came first. Hospitalizations of each subject were recorded and hospital records were evaluated for a possible flare of gouty arthritis. Person-year methods were used to calculate the rate of flares of gouty arthritis during hospitalizations and out-of-hospital. In addition, mixed logistic regression models with random subject effects (accounting for multiple hospitalizations per subject) were used to explore risk factors of in-hospital gout flares. Results: 429 patients with incident gout were followed for a mean of 4.2 years. The majority of patients were male (73%) and the mean age (SD) at gout onset was 59.7 (17.3). 169 patients had at least 1 hospitalization (cumulative incidence of first hospitalization was 39.1% for patients diagnosed in 1989-1992 compared to 43.1% for patients diagnosed in 2009-2010; p=0.56), with a total of 454 hospitalizations during the entire follow-up period. The rate of hospitalizations increased marginally from 2.26 per 10 person-years (py) in 1989-1992 to 3.49 per 10 py in 2009-2010 (rate ratio [RR]: 1.19; 95% confidence interval [CI]: 0.98, 1.45). 28 hospitalizations were complicated by a flare of gouty arthritis during a total of 3276 hospital days (9.0 total py) compared to 554 out-of hospital flares during 1784 py of follow-up. The rate of in-hospital flares was 85 per 100 py compared to 8.5 per 100 py out-of-hospital. Hospitalization was associated with a significantly increased risk of gout flares (RR: 10.2; 95% CI: 6.8, 14.5). In addition, the rate of in-hospital flares increased marginally over time (6.3 per 10 py in 1989-1992 vs 11.7 per 10 py in 2009-2010; RR: 1.85; 95% CI: 0.89, 4.00). Various possible predictors of gout flares during hospitalization were evaluated, including discontinuation of established uric acid lowering therapy, administration of IV fluids, ICU admission, use of diuretics and reason for admission, but none were identified as statistically significant predictors of in-hospital flares. Conclusion: Hospitalization represents a significant risk factor for flares of gouty arthritis in patients with a prior diagnosis of gout, although the absolute risk is still low. Future studies are needed to clarify which patient subgroups are at particular risk and if inpatient care related measures can help to prevent arthritic flares during hospitalization. Disclosure: N. Zleik, None; M. Elfishawi, None; Z. Kvrgic, None; C. J. Michet Jr., None; C. S. Crowson, None; E. L. Matteson, None; T. Bongartz, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/hospitalization-and-flare-risk-inpatients-with-established-gout-a-population-based-study-2
Abstract Number: 245
Seasonal Variation in Acute Gouty Arthritis: Data from Nationwide Inpatient Sample
Paras Karmacharya1, Ranjan Pathak2, Madan Aryal2, Smith Giri3 and Anthony Donato4, 1Internal Medicine, Reading Health System, WEST READING, PA, 2Internal medicine, Reading Health System, West Reading, PA, 3Internal medicine, University of Tennessee Health Science Center, Memphis, TN, 4Internal, Reading Health System, Salt Lake, UT First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Metabolic and Crystal Arthropathies Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Studies describing seasonal variations in acute gouty arthritis note a seasonal trend, but disagree on timing, with most showing a peak in spring months while others showing peaks later in the year. The peak serum uric acid (SUA) levels however, have been found to be in the summer months. This disparity has led to the hypothesis that the flares might be related to factors other than high SUA levels. Various theories on the effect of weather and immune system changes on the chronobiology of the equilibrium and precipitation of monosodium urate crystals have been proposed. We aimed to shed light on this question by examining the seasonal variation in the incidence of acute gouty arthritis in the US using a large inpatient database. Methods: We used the Nationwide Inpatient Sample (NIS) database to identify patients aged ≥ 18 years with primary diagnosis of acute gouty arthritis ICD-9-CM code 274.01 from 2009-2011 during hospitalization. We used the Edwards' recognition and estimation of cyclic trend method to study the seasonal variation of the incidence of acute gout and Z-test to compare the seasonal incidences. Results: A total of 28,172 hospitalizations with primary diagnosis of acute gouty arthritis were reported in during the period. The peak incidence of acute gout was seen in November (peak/low ratio 1.34, 95% CI 1.29-1.38, p0), no change (0) and improvement (2 consecutive visits (n=1,061 knees, 738 participants). Quantitative medial JSW was based on a semiautomated method and location specific (x=0.25). We compared a KL-based definition of AKOA, which accounts for changes throughout a knee, to 4 JSW-based definitions that are derived from previous latent class analyses: 1) stringent JSW (averaged): average JSW loss >1.05 mm/year over 4 years, 2) stringent JSW (consistent): JSW loss >1.05 mm/year for >2 years, 3) lenient JSW (averaged): average JSW loss >0.25 mm/year over 4 years, and 4) lenient JSW (consistent): JSW loss >0.25 mm/year for >2 years. We also defined AKOA as progression from no radiographic KOA to end-stage KOA (KL=3 or 4) within 4 years. We calculated kappa statistics between the JSW-based definitions and KL-based definition of AKOA. We then examined how the different definitions influenced the effect size of group differences (AKOA or no AKOA) of an injury during the first four years of the OAI, baseline age, baseline BMI, and average WOMAC pain score from baseline and the first four annual visits as a form of construct validity. Results: Over 4 years the incidence rate of AKOA was 0.7%, 1.2%, 18.1%, 24.7%, and 11.2% based on the stringent JSW (averaged and consistent), lenient JSW (averaged and consistent), and KL-based definitions. Everyone meeting the stringent JSW definition also met the KL-based definition. There was fair-moderate agreement between the lenient JSW (averaged) and KL-based definitions. KL-based definition led to larger effect sizes for injury, age, BMI, and average pain. Conclusion: A KL-based definition of AKOA may be ideal because it offers greater effect estimates for known risk factors for the condition. The performance of the KL-based definition may be related to the broader definition of joint deterioration compared with those focused on just joint space alone.
Disclosure: J. Driban, None; G. H. Lo, None; C. B. Eaton, None; L. L. Price, None; B. Lu, None; T. E. McAlindon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/best-performing-definition-ofaccelerated-knee-osteoarthritis
Abstract Number: 326
Older Adults without Extreme Obesity Are at Highest Risk for Accelerated Knee Osteoarthritis Jeffrey Driban1, Grace H. Lo2, Charles B. Eaton3, Lori Lyn Price4, Bing Lu5, Mary Barbe6 and Timothy E. McAlindon7, 1Tufts Medical Center, Boston, MA, 2VA HSR&D Center for Innovations in Quality, Effectiveness and Safety; Medical Care Line and Research Care Line; Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, 3Family Medicine and Community Health( Epidemiology), Alpert Medical School of Brown University, Pawtucket, RI, 4Clinical Care Research, Tufts Medical Center, Boston, MA, 5Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 6Temple University School of Medicine, Philadelphia, PA, 7Division of Rheumatology, Tufts Medical Center, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Osteoarthritis - Clinical Aspects Poster I: Treatments and Metabolic Risk Factors Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Accelerated knee osteoarthritis (AKOA) may be a unique subset of knee osteoarthritis (KOA). AKOA is more common among those who are older, overweight, or had a recent knee injury. These three risk factors interact to exacerbate an individual’s risk for AKOA. Identifying which subset of individuals are at most risk for AKOA will help clinicians recognize patients that need more frequent follow-up visits to ensure early detection of AKOA. Therefore, we explored age and body mass index (BMI) to identify a subset of individuals who are at high risk for AKOA compared with common KOA. Methods: In the Osteoarthritis Initiative we studied participants without KOA on their baseline radiographs (KellgrenLawrence [KL] < 2). We compared 2 groups: 1) AKOA: > 1 knee progressed to end-stage KOA (KL Grade 3 or 4) within 48 months and 2) common KOA: > 1 knee increased in radiographic scoring within 48 months (excluding those with AKOA). Age and BMI were collected at the baseline visit. A recent knee injury was a self-reported injury within a year prior to a knee meeting the definition of AKOA or common KOA. We reviewed 3-dimensional surface and contour graphs with age, BMI, and probability of AKOA versus KOA on the axes to identify groups that have the highest probability of AKOA compared with common KOA (see Figure). After we identified two possible subsets as high risk we conducted a logistic regression with AKOA as the outcome and age-BMI groups as the predictor
(adjusting for sex and recent knee injury). We also explored stratified analyses among those with and without a recent knee injury. Results: Among 1,637 participants, 52 (3.2%) individuals had AKOA and 184 (11.2%) had common KOA. We identified two high-risk sets of individuals (Figure 1B): 1) individuals > 65 years of age with BMI < 35kg/m2 (n = 64, 27%) and 2) individuals < 65 years of age with BMI > 32.5 kg/m2 (n = 43, 18%). We defined all other participants as low risk. Overall, older individuals with a BMI < 35kg/m2 were 3.5 times more likely to develop AKOA instead of common KOA than individuals at low risk (see Table). In contrast, younger individuals with a BMI > 32.5 kg/m2were not statistically more likely to develop AKOA instead of common KOA. These findings were consistent among those with and without a recent knee injury (see Table). Conclusion: While older age and greater BMI are associated with AKOA we found that older individuals with a BMI < 35kg/m2were more likely to develop AKOA than common KOA. Individuals with these characteristics who also report knee pain should be carefully monitored to detect early signs of AKOA.
Disclosure: J. Driban, None; G. H. Lo, None; C. B. Eaton, None; L. L. Price, None; B. Lu, None; M. Barbe, None; T. E. McAlindon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/older-adults-without-extremeobesity-are-at-highest-risk-for-accelerated-knee-osteoarthritis
Abstract Number: 327
The Relation of Plasma Vitamin K Status to Meniscal Pathology in Knee Osteoarthritis: The Multicenter Osteoarthritis Study Jia Liu1, Martin Englund2, Sarah Booth3, David T. Felson4, Michael C. Nevitt5, Cora E. Lewis6, James Torner7, Anyu Hu8 and Tuhina Neogi4, 1Boston Medical Center, Boston, MA, 2Clinical Epidemiology Unit, Orthopedics, Dept of Clinical Sciences Lund, Lund University, Lund, Sweden, 3HRNCA, Tufts Medical Center, Boston, MA, 4Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 5Epidemiology and Biostatistics, UCSF, San Francisco, CA, 6Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, 7University of Iowa, UIowa, Iowa City, IA, 8Clinical Epidemiology Research Unit, Boston University School of Medicine, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Osteoarthritis - Clinical Aspects Poster I: Treatments and Metabolic Risk Factors Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Vitamin K is an essential cofactor in bone and cartilage mineralization. Low serum vitamin K has been associated with increased prevalence of hand and knee osteoarthritis (OA), higher risk of developing knee OA and cartilage lesions, and, in one study, worsening of meniscal lesions; however, incidence of meniscal damage was not assessed. Meniscal damage is a potent risk factor for knee OA, and severe knee OA is associated with meniscal
damage. We therefore sought to identify whether vitamin K status was associated with the prevalence and incidence of meniscal pathology on MRI. Methods: The Multicenter Osteoarthritis (MOST) Study is a NIH-funded longitudinal cohort study of adults with or at high risk for developing knee OA. Participants had knee x-rays and 1.0T MRIs at 0 and 30 months. MRI evidence of meniscal pathology was evaluated using WORMS. Meniscal integrity was graded on a 0-4 scale in 3 subregions of the medial and lateral menisci, respectively, and medial and lateral meniscal extrusion were graded on a 0-2 scale. We defined meniscal pathology as any abnormality of meniscal integrity (score ≥1 in any subregion) or meniscal extrusion (medial or lateral score ≥1). Vitamin K status was determined by plasma phylloquinone levels at baseline, and categorized as insufficient (0.24) or six years (p>0.16) or with all fractures, osteoporotic fracture sites other than the spine and hip (other fractures) and spine fractures (p> 0.13). Sodium intakes above the median were associated with significant increases in BMD at the total body from baseline to three years (p=0.02), though changes from baseline to six years were not significant (p=0.36). Sodium intake above the median was also associated with fewer hip fractures (p=0.03). Levels of sodium intake above or below currently recommended guidelines for cardiovascular disease (2300 mg /day) were not associated with changes in BMD at any skeletal site from baseline to three (p> 0.66) or six years (p> 0.74) or with incident fractures (p≥0.70). There was no association of sodium intake with incident fractures after adjusting for potassium intake (p≥0.30). Calcium intake did not modify the association between sodium intake and changes in BMD or risk of incident fracture (p≥0.20). Conclusion: Adherence to current population-based recommended intakes for sodium intake is unlikely to significantly impact osteoporosis. The surprising association of higher sodium intakes with fewer hip fractures merits further study. Disclosure: L. Carbone, None; K. Johnson, None; Y. Huang, None; M. Pettinger, None; T. Fridtjof, None; J. A. Cauley, None; C. Crandall, None; L. Tinker, None; M. LeBoff, None; J. Wactawksi-Wende, None; M. Bethel, None; W. Li, None; R. Prentice, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sodium-intake-and-osteoporosisfindings-from-the-womens-health-initiative
Abstract Number: 362
Reference Curves of Bone Parameters Obtained By High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Healthy Women from 20 to 85 Years Old Jackeline Couto Alvarenga1, Henrique Fuller2, Sandra G. Pasoto2, Stephanie Boutroy3 and Rosa M R Pereira4, 1Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 3INSERM U831 and Université de Lyon, Lyon, France, 4Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Osteoporosis and Metabolic Bone Disease - Clinical Aspects and Pathogenesis Poster Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Bone is a dynamic tissue, and its formation and resorption are continuous processes that promote changes throughout the life of the organism, and changes in bone microstructure contribute to fracture risk. High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) can assess microstructural and biomechanical properties of human distal end. Faced with so multitude of applications and perspectives of HR-pQCT, it is necessary to establish normal standard curves. The aim of this cross-sectional study is to establish normal values related to age, weight and height using HR-pQCT regarding volumetric bone mineral density (vBMD), microstructure, cortical porosity and estimated bone strength at the distal radius and tibia from a women population aged 20 to 85 years.
Methods: References curves were calculated in 450 healthy women (> 50 women per decade). The HR-pQCT acquisitions (XtremeCT, Scanco Medical) were performed using the standard scanning protocol. Statistical analysis including linear regression models were developed to predict the values of the twenty normal curves measured according to age, weight and height. The outcome variables used in our analyses included the following: Volumetric bone density parameters (mg HA/ccm): trabecular bone density (Tb.vBMD), cortical bone density (Ct.vBMD); Bone structure parameters: number of trabeculae (Tb.N, 1/mm), trabecular thickness (Tb.Th, mm), trabecular separation (Tb.Sp, mm), cortical thickness (Ct.Th, mm); Cortical porosity parameters: cortical porosity (Ct.Po, 1), mean cortical pore diameter (Ct.Po.Dm, mm); Finite element analysis (FEA): stiffness (S, kN/mm), estimated failure load (F.Load, N). Results: Evaluation of the distal radius by HR-pQCT: All parameters showed linear curves with age, except for Ct.Po, S and F.Load. Positive correlations were observed between stiffnewomenss and Tb.vBMD (r: 0.644, p < 0.001), Ct.vBMD (r: 0.521, p < 0.001), Tb.N (r: 0.245, p < 0.001), Tb.Th (r: 0.616, p < 0.001), Ct.Th (r: 0.619, p < 0.001), Ct.Po.Dm (r: 0.140, p < 0.001) and F.Load (r: 0.995, p < 0.001). In contrast, weak negative correlations were detected between S and Tb.Sp (r: -0.312, p < 0.001) and Ct.Po (r: -0.162, p= 0.015). Evaluation of the tibia by HRpQCT: All obtained curves were linear, except for Ct.vBMD, Ct.Th and Ct.Po. The cortical density and thickness showed a plateau until about 50 years of age, following by a decreasing curve. Positive correlations were observed between stiffness and Tb.vBMD (r: 0.571, p < 0.001), Ct.vBMD (r: 0.316, p < 0.001), Tb.N (r: 0.298, p < 0.001), Tb.Th (0.355, p < 0.001), Ct.Th (r: 0.392, p < 0.001) and F.Load (r: 0.955, p < 0.001). Moreover, negative correlations were found between S and Tb.Sp (r: -0.354, p < 0.001) and Ct.Po (r: -0.273, p < 0.001). Conclusion: This study established a set of reference data for HR-pQCT parameters in a heathy women population, which will be useful for interpreting clinical data from patients in clinical practice and in future studies. Disclosure: J. C. Alvarenga, None; H. Fuller, None; S. G. Pasoto, None; S. Boutroy, None; R. M. R. Pereira, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reference-curves-of-boneparameters-obtained-by-high-resolution-peripheral-quantitative-computed-tomography-hr-pqct-in-healthy-womenfrom-20-to-85-years-old
Abstract Number: 363
Determination of the Osteoporotic Vertebral Fractures By a New Quantitative Approach: Intervertebral Volume Index Omer Kuru1, Yasemin Ulus2, Halil Sen2, Bunyamin Sahin3 and Ayhan Bilgici2, 1Physical Medicine And Rehabilitation Division of Rheumatology, Ondokuz Mayis University School of Medicine, Samsun, Turkey, 2Physical Medicine and Rehabilitation Division of Rheumatology, Ondokuz Mayis University School of Medicine, Samsun, Turkey, 3Anatomy, Ondokuz Mayis University School of Medicine, Samsun, Turkey First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Osteoporosis and Metabolic Bone Disease - Clinical Aspects and Pathogenesis Poster Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Vertebral fractures caused by osteoporosis are quite common and have a negative effect on quality of the life. But they may not be clinically detectable. Computed tomography (CT) is an appropriate method in examining and evaluating the vertebral fractures because it shows bone details accurately, clearly and quickly.
Stereology is a science which is used to obtain quantitative data about the structure using two-dimensional section from the three dimensional structures. In this study, we aimed to describe a new method that demonstrates objectively the decrease percentage of the volume of the fractured vertebral body according to the average volume of the neighboring vertebrae using the volume intervertebral volume index (IVF). Methods: Forty women, who admitted to the Ondokuz Mayis University, Department of Physical Medicine and Rehabilitation and who were diagnosed with osteoporosis by bone mineral density (BMD) and osteoporotic vertebral compression fracture by routine thoracolumbar radiographs, were included in the study. CT images of the patients were taken with 3 mm thickness in axial plane were converted to the sagittal orientation. Vertebrae volumes were calculated using the Cavalieri principle, which is one of the stereological methods in ImageJ software. Reduction in the volume of the fractured vertebra was calculated as percentages based on above and below vertebral volumes. Results: It was determined that the measured volume of the fractured vertebra at each fracture level decreased by 67.70% compared to the expected vertebral volume that was calculated according to volumes of the above and below vertebrae of the fractured vertebra. In all patients, significant differences were determined between the average detected volume and the expected volume of the fractured vertebrae (p 0. Within the SA cohort, 13% went on to develop ESRD, of which 9% required transplant, strikingly higher than North American peers. (Table 3) Conclusion: The PULSE cohort is the largest registry of pSLE patients in Africa to date. Children in SA receive different therapy and demonstrate a striking increase in poor renal outcomes, end stage renal disease, and irreversible organ damage compared to North American peers. These differences may be due to treatment, health care access, racial predisposition, or a combination of factors. Further prospective research is required to determine the burden of pSLE in South Africa, and identify risk factors for poorer outcome in this high risk population. Table 1. Features at Enrollment PULSE CARRA Mean age of SLE diagnosis (mean, SD) Average disease duration, yrs (mean, SD) % Female (n) % White (n) % Other (n) % Age ≤13 at diagnosis (n) % ANA positive (n) % Anti-dsDNA positive (n)
N=72 11.5 (3.5)
N=982 12.4 (3.2)
2.4 ( 3.2)
82.3 (56) 6 (4) 3 (2) 75 (53) 96 (69)
82.5 (810) 45 (426) 20 (190) 51 (475) 91 (888)
% Lupus Nephritis (n) 61 (44) Average SLEDAI Score [range 0- 20.6 (9.9) 105] (SD) % renal biopsy (n) 58 (41) % of biopsied patients with ISN 100 (41) classification
41 (409) 4.8 (1.9) 44 (428) 65 (280)
Table 2. Treatment History at Enrollment PULSE CARRA N=72
% steroids (n) 93 (66) 94 (917) 0.725 % antimalarial (n) 78 (54) 92 (853) 0.001 =3 outpatient visit claims with an ICD-9 primary diagnosis code for SLE of 710.0, each recorded at least 30 days apart. We categorized race/ethnicity as: white, African-American, Latino and other. We conducted unadjusted and adjusted logistic regression analyses to compare the following between racial/ethnic groups: 1) depression diagnoses and 2) antidepressant use. Covariates included: age, sex, urban vs. rural location, presence of SLE nephritis and central nervous system (CNS) disease, defined as seizures or stroke. Results: We identified 970 adolescents with SLE; 15% were white, 42% African American, 27% Latino and 16% of other races/ethnicities. The mean age was 14.7 (SD=2.0), 83% were female and 85% were of urban location. Nephritis was present in 36% and CNS disease in 16%. Seventeen percent of the sample had depression diagnosis and 21% used an antidepressant. In adjusted analyses, African-Americans were less likely than whites to have a depression diagnosis (OR=0.5, 95%CI 0.3-0.8, p 0 in 80% vs. 58%; p = 0.002). Median PGA was also significantly higher in the REM group than in the NHW group (2 [IQR: 1-3] vs. 1 [IQR: 0-3]; p = 0.015). No differences were noted for patient-reported outcomes (pain scale, global well-being scale, quality of life, Childhood Health Assessment Questionnaire). No differences were noted in other potential confounders of PGA, including: age at onset and first rheumatologist visit; time from onset to first rheumatology visit; lesion location; ECMs; laboratory tests (i.e. ANA, creatine kinase, aldolase); present/past systemic immunosuppressive treatment; or hemifacial atrophy. Conclusion: REM group LS patients enrolled in this large, multicenter cohort were more likely than NHW to have active disease. Differences in rates of disease subtypes (linear trunk/limb vs. face/scalp) and socioeconomic status (e.g. annual household income) were also noted and their possible contribution to the relationship of race/ethnicity and disease activity warrants further investigation. Future studies should collect detailed sociodemographic data, examining both clinical and social determinants of outcomes in LS. Disclosure: K. Ardalan, None; N. Hershey, None; J. Yabes, None; K. S. Torok, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-of-race-ethnicity-andoutcomes-in-pediatric-localized-scleroderma-possible-differences-in-disease-activity
Abstract Number: 419
Development and Preliminary Validation of a New Composite Disease Activity Measure for Juvenile Dermatomyositis Alessandro Consolaro1, Giulia Camilla Varnier1, Cristina Ferrari1, Jaime De Inocencio2, Adele Civino3, Marija Jelusic-Drazic4, Elena Tsitsami5, Jelena Vojinovic6, Balahan Makay7, Graciela Espada8, Clara Malattia1, Susan Maillard9, Alberto Martini1, Clarissa Pilkington10, Angelo Ravelli1,11 and Kiran Nistala12, 1Pediatria II, Istituto Giannina Gaslini, Genova, Italy, 2Hospital 12 de Octubre, Madrid, Spain, 3Ospedale Cardinale G. Panico, Tricase, Italy, 4University Hospital Center, Zagreb, Croatia, 5First Department of Pediatrics, Athens University Medical School, Athens, Greece, 6Faculty of Medicine, University of Nis, Nis, Serbia, 7Pediatric Rheumatology, Eylul University, Izmir, Turkey, 8Rheumatology Section, Childrens Hosp Ricardo Gutierrez, Buenos Aires, Argentina, 9Paediatric Rheumatology, Great Ormond Street Hospital NHS Foundation Trust for Children, London, United Kingdom, 10Rheumatology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, 11University of Genova, Genova, Italy, 12Centre for Rheumatology, University College London, London, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015
Session Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster I: Lupus, Scleroderma, JDMS Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Evaluation of the level of disease activity is a fundamental component of the clinical assessment of children with JDM. The global tools that are currently available for the assessment of the overall disease activity in JDM are centered on physician’s evaluation, neglecting parent’s or child’s perception. Furthermore, these instruments are lengthy and complex. There remains the need for a concise and easily administered tool that provides an absolute measure of disease activity for use in future trials in JDM. Aim of the study was to develop and test a new composite disease activity score for JDM, named the Juvenile Dermatomyositis Activity Index (JDMAI) Methods: The JDMAI includes 4 measures: 1) physician global assessment of disease activity on a 0-10 VAS, 2) parent/patient global assessment of well-being on a 0-10 VAS, 3) muscle strength assessment, and 4) cutaneous disease activity. Validation analyses were conducted on 140 patients included in a multinational study and were based on evaluation of construct validity, responsiveness to change, and discriminant validity. Four versions of the JDMAI were tested, which differed items 3) and 4). Three versions included the hybrid MMT/CMAS (hMC), reversed and divided by 10, as measure of muscle strength (range 0-10), and the cutaneous domain of the DAS (range 0-9) (JDMAI-1), a cutaneous VAS (range 0-10) (JDMAI-2), or the skin involvement type and distribution items of the DAS (range 0-7) (JDMAI-3) as measures of skin activity. A fourth version of the score (JDMAI-4) included the 3 CMAS items of the hMC (head lift; sits up, floor rise) (range 0-20) for muscle strength and the skin involvement and distribution items of the DAS for skin activity. Results: Construct validity: Spearman’s correlations of all JDMAI versions were: strong (r > 0.7) with total DAS (0.80 0.90), parents’ disease activity VAS (0.73 to 0.80), and CHAQ (0.72 to 0.80); moderate (r 0.4-0.7) with CMAS (-0.63 to 0.65, -0.80 for JDMAI-4), pain VAS (0.55 to 0.60), fatigue VAS (0.62 to 0.70); poor (r < 0.4) with LDH (0.27 to 0.32), and ESR (0.35 to 0.38). Correlation of all JDMAI versions with the Myositis Damage Index and CPK was not significant. Responsiveness to change between 2 consecutive visits : SRM ranged from 0.72 (JDMAI-1) to 0.78 (JDMAI-4). Discriminant validity: all JDMAI versions discriminated between patients rated in remission, continued active disease, and flare by the physician (p < 0.001) and by the parent (p < 0.001), and between patients with high, moderate, or low disease activity according to the physician (p < 0.001). Conclusion: All JDMAI versions showed good construct validity and responsiveness to change, and excellent discriminant validity. We have shown that the JDMAI is a valid instrument for the assessment of disease activity in JDM and is, therefore, potentially applicable in standard clinical care, observational studies, and clinical trials. Disclosure: A. Consolaro, None; G. C. Varnier, None; C. Ferrari, None; J. De Inocencio, None; A. Civino, None; M. Jelusic-Drazic, None; E. Tsitsami, None; J. Vojinovic, None; B. Makay, None; G. Espada, None; C. Malattia, None; S. Maillard, None; A. Martini, None; C. Pilkington, None; A. Ravelli, None; K. Nistala, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-and-preliminaryvalidation-of-a-new-composite-disease-activity-measure-for-juvenile-dermatomyositis
Abstract Number: 420
Description of the Juvenile Localized Scleroderma Subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry
Eveline Y. Wu1, Suzanne C. Li2, Kathryn S. Torok3, Yamini Virkud4, Robert C. Fuhlbrigge5, C. Egla Rabinovich6 and CARRA Registry Investigators, 1Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Pediatrics, Hackensack University Medical Center, Hackensack, NJ, 3Pediatric Rheumatology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 4Pediatrics, Massachusetts General Hospital for Children, Boston, MA, 5Pediatric Rheumatology, Boston Children's Hospital, Boston, MA, 6Pediatric Rheumatology, Duke University Medical Center, Durham, NC First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster I: Lupus, Scleroderma, JDMS Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Localized scleroderma (LS) is a chronic inflammatory and fibrosing skin disease. We present baseline data on the juvenile LS (jLS) cohort from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, a multicenter observational pediatric rheumatic disease registry. Methods: Descriptive statistics were used for demographic, clinical and laboratory features. Data analysis included the two-sample t-test, chi-square test, Fisher’s exact test, logistic regression, and analysis of variance as appropriate. Results: Of 386 children in the database, 76% were female and 80% were Caucasian. Mean age at onset was 8.2 yr (± 4.2). Mean age at first pediatric rheumatology (PRH) evaluation was 9.6 yr (± 4.1), yet 18% had ≥ 2 yr delay from onset to first PRH visit. Linear scleroderma (LiS) was the most common subtype (54%), followed by circumscribed morphea (CM) (16%), generalized morphea (GM) (9%), eosinophilic fasciitis (1%), and pansclerotic morphea (1%). 19% of children had mixed subtype, and LiS-CM was the most frequent combination (61%). Among LiS patients with face-scalp localization (34%), neurologic and ocular diseases were reported in 11% and 4%, respectively. ANA positivity was found in 48% tested and was not associated with disease subtype or age at onset. ANA positivity, however, was associated with features of non-cutaneous disease damage, specifically joint contracture (p=0.04), muscle atrophy (p=0.01), and extremity shortening (p1st line ABA treatment were 68.7% and 57.9%, respectively (p=0.084). There was a trend for a higher one year drug survival rate among anti-CCP (+) patients as compared to those who were anti-CCP (-) (73.1% versus 56.4%; p=0.087), whereas one-year drug survival rates were very similar for RF (+) and RF (-) patients at 63.4% and 64.8%, respectively (p=0.462) Drug survival curves for RF (+)/(-) and Anti-CCP (+)/(-) groups are given in Figure 1 and 2, respectively.
Figure 1. Drug survival curve in RF (+) and (-) patients.
Figure 2. Drug survival curve in anti-CCP (+) and (-) patients Conclusion: One year drug survival rate of ABA among patients enrolled in the TURKBIO registry is similar to those which has been reported in some other European countries. One year drug survival rates appear to be better among patients who are positive for anti-CCP, but not for RF as compared to those who are negative for the corresponding antibodies, which needs to be explored in future studies. Disclosure: I. Ertenli, None; O. Karadag, None; Y. Pehlivan, None; E. Dalkilic, None; A. M. Onat, None; B. Kisacik, None; G. Can, None; S. Akar, None; S. Capar, None; U. Kalyoncu, None; M. F. Oksuz, None; E. F. Tarhan, None; N. Akkoc, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-effect-of-rheumatoid-factor-andanti-cyclic-citrullinated-peptide-positivity-on-drug-survival-of-abatacept-in-patients-with-rheumatoid-arthritis-inroutine-care-the-results-from-turkbio-registry
Abstract Number: 460
Changes in Body Composition and Metabolic Profile during Treatment with Tocilizumab in Patients with Rheumatoid Arthritis Anne Tournadre 1, Bruno Pereira2, Frederic Dutheil3, Vincent Sapin4, Charlotte Giraud5, Sandrine MalochetGuinamand6, Thomas Frayssac7, Sylvain Mathieu5, Jean-Jacques Dubost8 and Martin Soubrier8, 1Rheumatology, UNH-UMR 1019 INRA University of Auvergne and Rheumatology department CHU Clermont-Ferrand, ClermontFerrand, France, 2Biostatistics unit (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France, 3Preventive and Occupational Medicine, CHU G. Montpied Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological conditions EA3533, Clermont-Ferrand, France, 4Biochemistry and Molecular Biology Department CHU Clermont-Ferrand, Clermont Université, Université d'Auvergne, EA7281, Clermont-Ferrand, France, 5Rheumatology, Rheumatology department CHU Clermont-Ferrand, Clermont-Ferrand, France, 6Rheumatology Department,, Rheumatology department CHU Clermont-Ferrand, Clermont-Ferrand, France, 7Rheumatology, Rheumatology department CHU Clermont-Ferrand, Clermont-ferrand, France, 8Rheumatology department CHU Clermont-Ferrand, Clermont-Ferrand, France First publication: September 29, 2015
SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Rheumatoid arthritis (RA) is characterized by increased cardiovascular risk and metabolic changes including cachectic obesity, insulin resistance, dyslipidemia. DMARDs decrease inflammation and could thus improve cardiovascular risk but their effects on body composition and metabolic profile remain unclear. We investigated the effects of tocilizumab, an inhibitor of the IL6 pathway on body composition and metabolic profile in active RA. Methods: We conducted an open 1-year follow-up study of 21 patients with active RA treated with tocilizumab. Waist circumference (WC), body mass index (BMI), body composition (dual-energy x-ray absorptiometry), lipid profile, fasting glucose, blood pressure, and arterial stiffness were measured at baseline when started tocilizumab, 6 months and 1 year of treatment. At baseline, RA patients were compared with 21 controls matched for age, sex, BMI and metabolic syndrome. The longitudinal data were explored using a random-effect models. To assess the issue of missing data, the estimation methods developed by Verbeke and Molenberghs were considered in this study. Results: 21 RA patients, including 16 women with a mean age of 57.8 ± 10.5 years were included. RA duration was 8.5 years [IQR 1.7 – 21.5]. At baseline, 19 patients received a DMARD, 14 steroids, 11 cholesterol-lowering drug, 1 anti-diabetic drug, 6 antihypertensive medication. 18 patients have previously received at least one biologic. The mean DAS 28 at baseline was 4.7 ±1 and decreased significantly at 6 and 12 months (2.92±0.8 and 2.8±1.5 respectively, p=18 years) individuals with a diagnosis of RA ( ICD 9 code) at 2 or more outpatient visits from 1999 to 2009 ,were identified. Only patients with at least one lipid level measured at 120-180 days prior to staring HCQ were included. Lipids levels at pre start date of HCQ and post start date of HCQ (120-180 days) were compared using students t-test and then adjusted for age, sex, race, CRP and statin use with multivariable regression (ANOVA/ANCOVA) for the change in different lipid levels. To give equal weight to covariables we conducted an analysis of marginal means for race in each lipid level. All analyses were performed with STATA 11. Results: Gender
Yes on Statin No on Statin All 402 (15.61%) 2174 2576 (84.39%)
Demographics Lipid changes in HCQ users
(84.39%) Male (N/%) Age 69 (9.6) 64(12.20) (mean/SD) Race 369 (15.50%) 1868 2237 (83.50%) White (N/%) AA (N/%) 28 (8.26%) 312 (91.74%) 340 Others (N/%) 13 (3.06%) 123 (4.92%) 136 Unknown 15 (3.53%) 197 (7.88%) 212 (N/%) Pre-CRP 16.13 (13.53) 5.16 (12.14) mg/dl (mean/SD) Post-CRP mg/dl
Pre-mean Post-mean Total (SE) (SE) Difference Cholesterol 176.17 171.65 4.52 (.87) (.90) LDL 103.77 98.86 (.76) 4.91 (.76) HDL 45.80 (.32) 46.18 (.32) -0.38 Non-HDL 130.37 125.46 4.91 (.85) (.86) AI 4.17 (.38) 4.0 (.03) 0.17
0.00 0.00 0.06 0.00 0.00
Lipid changes in HCQ users by statin use groups. Yes Statins No Statins
11.22 (37.9) 5.90(17.94)
Change in Cholesterol Change in LDL Change in HDL Change in non HDL Change in AI
Mean (SD) 2.32 (37.72)
Mean (SD) 2.41 (33.18)
4.76 (30.52) -0.35 (9.78) 2.92 (37.069)
5.09 (31.78) - 0.41 (1.09) 5.52 (32.17)
After adjusting for sex, age, race, statin use and post crp values > 10mg/dl using a linear regression, the factor driving the change in the different lipid levels was race (p values for total cholesterol (TC) 0.006,LDL 0.09, non-HDL 0.03, TC/HDL 0.08 and HDL 0.17). When looking at race individually using marginal means analysis the race in the subgroup others was the more influential. Conclusion: Our results suggest gender and race play a role in the effects of HCQ on lipid profiles in RA patients.Use of HCQ in males is found to be associated with positive changes in the lipid profiles independent from the use of statins. There is a suggestion that whites and African Americans might be less susceptivle to HCQ effect on lipid profiles. Disclosure: M. Guevara, None; B. NG, None; N. Gove, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/race-plays-a-role-in-influencingthe-modest-lipid-lowering-effects-of-hydroxychloroquine-in-patients-with-rheumatoid-arthritis-independent-of-statinuse
Abstract Number: 485
Evaluate the Dose Efficacy Response Relationship of Baricitinib in Patients with Rheumatoid Arthritis Xin Zhang, Laiyi Chua, C. Steven Ernest II, William Macias, Terence Rooney and Lai San Tham, Eli Lilly and Company, Indianapolis, IN First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I
Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Baricitinib (Bari) is an oral inhibitor of Janus kinases (JAK) selective for JAK 1 and 2. It has demonstrated dose-dependent efficacy in patients with moderate-to-severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate in multiple phase 2 studies. The objective of this analysis was to characterize the dose/exposure-response (D/E-R) relationship of Bari to optimize selection of doses and dose regimens for the phase 3 program. Methods: Pharmacokinetics (PK) and efficacy data are available in patients with RA from two Phase 2 studies, Study JADA (n=278, Keystone E, et al.) and Study JADN (n=143, Tanaka Y, et al.), respectively. Study JADA used doses of 1, 2, 4, and 8 mg QD for up to 24 weeks and 2 mg BID for 12 weeks, and Study JADN used doses of 1, 2, 4, and 8 mg QD for up to 12 weeks. A Population PK (PopPK) model was developed to characterize plasma concentration-time profiles and identify potential covariates using NONMEM (version 7.2). A semi-mechanistic population PK/pharmacodynamic (PK/PD) model was developed to describe the time course and D/E-R relationship for the key efficacy endpoints, ACR20/50/70 and DAS28-CRP response rates. A placebo effect was accounted for in both PD models. A sequential PK and PK/PD analysis approach was used. The developed PK/PD model was subsequently applied to simulate ACR20/50/70 and DAS28-CRP response rates following various doses and dosing regimens (QD vs BID) to help optimizing dose selection for phase 3 studies. Results: The models adequately described the PK and the longitudinal dose/exposure-response relationships for ACR20/50/70 and DAS28-CRP for all regimens tested in the phase 2 studies. The mean terminal half-life of BARI was estimated to be approximately 14 hours. Renal function was identified as a significant covariate on the clearance of BARI. No patient factors had a significant impact on the PK/PD relationship. PD steady state was attained approximately 12 weeks after treatment for all endpoints. Based on the dose/response curve, 4 mg approached the maximum effect and offered additional efficacy benefits over 2 mg. Simulations suggested that at the same total daily doses, QD and BID dosing regimens achieved similar average plasma concentrations at steady state. In addition, the efficacy responses were comparable between the QD and BID dosing regimens for all efficacy endpoints at the same total daily doses based on the simulations. Conclusion: Based on modeling and simulations with phase 2 data over a dose range of 1-8 mg (QD and BID), 4 mg and 2 mg QD were selected for further investigation for the BARI phase 3 studies, with 4 mg QD identified as the preferred phase 3 dose. At the same total daily dose, splitting the dose into a BID regimen does not provide any advantage over QD dosing for any of the efficacy endpoints. References: Keystone E, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015;74(2):333-340. Tanaka Y, et al. Efficacy and safety of baricitinib in Japanese RA patients during a 52 week extension phase. Art Rheum. 2014;66(11):S652. Disclosure: X. Zhang, Eli Lilly and Company, 1,Eli Lilly and Company, 3; L. Chua, Eli Lilly and Company, 1,Eli Lilly and Company, 3; C. S. Ernest II, Eli Lilly and Company, 1,Eli Lilly and Company, 3; W. Macias, Eli Lilly and Company, 1,Eli Lilly and Company, 3; T. Rooney, Eli Lilly and Company, 1,Eli Lilly and Company, 3; L. S. Tham, Eli Lilly and Company, 1,Eli Lilly and Company, 3. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluate-the-dose-efficacyresponse-relationship-of-baricitinib-in-patients-with-rheumatoid-arthritis
Abstract Number: 486
Persistence Among Rheumatoid Arthritis Patients Initiating Intravenous
or Subcutaneous Anti-Tumor Necrosis Factor Therapy in a Large US Registry Cohort Dennis Parenti1, Shelly Kafka1, George W. Reed2, Jeffrey D. Greenberg2,3 and Raphael DeHoratius1,4, 1Janssen Scientific Affairs, LLC, Horsham, PA, 2Corrona, LLC, Southborough, MA, 3NYU School of Medicine, New York, NY, 4Kimmel School of Medicine, Thomas Jefferson University, Philadelphia, PA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: The objective of this analysis was to examine persistence with intravenous (IV) and subcutaneous (SC) anti-TNF therapies among rheumatoid arthritis (RA) patients (pts) within the US CORRONA RA registry. Methods: A retrospective analysis from the CORRONA RA registry was used for analyses. Adult RA pts (biologicnaïve and biologic-experienced) with moderate-to-severe RA (CDAI>10) who initiated anti-TNF biologics within the CORRONA registry after June 1, 2009 and had ≥6 months of follow up were eligible. Pts receiving IV anti-TNF therapy were compared with those receiving SC anti-TNF therapy. Propensity scores (PS) were generated to match IV anti-TNF initiators to SC anti-TNF initiators, stratified by line of therapy. Variables used for PS matching were based on characteristics with standardized differences of ≥0.1 including age, gender, duration of RA, work status, smoking status, insurance, prednisone use, monotherapy, prior serious infections, patient global, morning stiffness, year of initiation, time from initiation to 6 month visit, and prior number of biologics to control for population imbalances. Time-varying hazard ratios (HR) comparing persistence in matched IV vs SC through 48 months were estimated and stratified by line of therapy. Results: A total of 1544 pts were included (772 each for IV and SC therapy). In each treatment group, 387 pts were bio-naïve, 220 had received 1 prior biologic, and 165 had received ≥2 prior biologics. Among all pts, significantly greater proportions of patients receiving IV therapy remained on that agent compared with pts receiving SC therapy (p=0.002) during the first 12 months (HR=0.76 [0.63-0.90]). No significant differences in persistence were observed from 24 – 48 months (HR=1.09 [0.88-1.35], p=0.45) (Figure 1). Similar results were observed for pts who were biologic-naïve (0-12 mons: HR=0.69 [0.52-0.90], p=0.007) and who had received 1 prior biologic (0-12mons: HR=0.80 [0.59-1.10], p=0.17). For pts who had received ≥2 biologics, there was no significant difference in persistence between patients receiving IV or SC anti-TNF therapy. Conclusion: Within the first 12 months of initiating anti-TNF therapy, pts receiving IV therapy who were biologicnaïve or had received only one prior biologic were more likely to remain on treatment compared with those receiving SC anti-TNF agents. These results may have implications on cost savings, in the first year of treatment, that need to be investigated in further studies. Figure1. Persistence estimates for matched populations.
Disclosure: D. Parenti, Janssen Scientific Affairs, LLC, 3; S. Kafka, Janssen Scientific Affairs, LLC, 3; G. W. Reed, Corrona, LLC, 3; J. D. Greenberg, Corrona, LLC., 3,Corrona, LLC., 1,AstraZeneca, Pfizer, Celgene, Novartis, Genentech, Janssen, 5; R. DeHoratius, Janssen Scientific Affairs, LLC, 3. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/persistence-among-rheumatoidarthritis-patients-initiating-intravenous-or-subcutaneous-anti-tumor-necrosis-factor-therapy-in-a-large-us-registrycohort
Abstract Number: 487
Early Rheumatoid Arthritis Patients in the Worse Disease Trajectory Group Fail to Achieve Improvement in Physical Function Cheryl Barnabe 1, Ye Sun2, Susan J. Bartlett3,4, Gilles Boire5, Carol Hitchon6, Edward C. Keystone7, Boulos Haraoui8, J Carter Thorne2, Diane Tin9, Janet E. Pope10, VP Bykerk11 and CATCH Investigators, 1Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, 2University of Toronto, Toronto, ON, Canada, 3Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, 4Medicine , Divisions of Clinical Epidemiology, Rheumatology, Respirology, McGill University, Montreal, QC, Canada, 5Department of Medicine/Division of Rheumatology, Université de Sherbrooke, Sherbrooke, QC, Canada, 6Department of Rheumatology, University of Manitoba, Winnipeg, MB, Canada, 7Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 8Institut de Rhumatologie, Montreal, QC, Canada, 9The Arthritis Program, Southlake Regional Health Centre, Newmarket, ON, Canada, 10University of Western Ontario, London, ON, Canada, 11Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM
Background/Purpose: Disease trajectories in early rheumatoid arthritis (ERA) are characterized by differences in absolute levels of disease activity and rates of improvement, with patients in the worse disease trajectories experiencing worse quality of life outcomes and persistent fatigue. Our objective was to determine if the magnitude of improvements in physical function, as measured by the Health Assessment Questionnaire (HAQ), also vary in the heterogeneous disease trajectories. Methods: Cluster-based trajectory modeling identified 5 mutually exclusive ERA disease activity trajectories by posterior membership probability using DAS28 over 24 months (described in Table 1). Baseline values and mean changes in the HAQ scores were examined for differences by trajectory group using ANCOVA, with adjustment for covariates (age, sex, number of comorbidities, low income, smoking, race). Results: The cohort includes 1586 patients (mean 54 years, 181 days of symptoms, 73% female, 82% Caucasian, 18% smokers, 70% seropositive). Half (50%) begin in high disease activity state (DAS), of which only 20% rapidly reach remission (Group 1). Group 5 only achieves moderate disease activity by 24 months, despite higher frequency of use of steroids and biologic therapy. HAQ scores were similar between Groups 1, 4 and 5 at baseline (Table 1). In Group 1 scores improve by 1.08 (SD 0.68) by 12 months but in Group 5 the HAQ fails to reach the minimal clinically important difference for improvement (0.22) and worsens from month 12 to 24 (Figure 1). Conclusion: Novel strategies are needed to identify which patients are at risk for disparate outcomes so that effective care plans can be enacted to preserve function. Table 1. Mean (SD) HAQ Scores at Baseline and Change Over 24 Months, by Trajectory Group Baseline Change Group 1 (HDAS 1.21 (0.70) -1.08 (0.68) to REM) Group 2 (MDAS 0.54 (0.53) -0.34 (0.51) to REM) Group 3 (MDAS 0.83 (0.62) -0.34 (0.61) to LDAS) Group 4 (HDAS 1.39 (0.65) -0.71 (0.78) to LDAS) Group 5 (HDAS 1.34 (0.64) -0.13 (0.66) to MDAS) Legend: HDAS high disease activity state; REM remission; MDAS moderate disease activity state; LDAS low disease activity state Figure 1. HAQ Scores by Trajectory Group, months 0-24
Disclosure: C. Barnabe, None; Y. Sun, None; S. J. Bartlett, PCORI, 2,NIH, 9; G. Boire, None; C. Hitchon, Health Sciences Centre Foundation, 2; E. C. Keystone, Janssen Inc., 2,Abbott/AbbVie, 5,Amgen, 2,Bristol-Myers Squibb, 5,Janssen Inc., 5,Hoffmann-La Roche, Inc., 5,Janssen Inc., 2,Janssen Inc., 5,Merck Pharmaceuticals, 5,Merck Pharmaceuticals, 5,Pfizer Pharmaceuticals, 5,Pfizer Pharmaceuticals, 5; B. Haraoui, Abbott, Amgen, BMS, Janssen, Pfizer, Roche and UCB Pharma, 2,Abbott, Amgen, BMS, Janssen, Pfizer, Roche and UCB Pharma, 5,Abbott, Amgen, BMS, Janssen, Pfizer, Roche and UCB Pharma, 8; J. C. Thorne, Amgen, Canada, 5; D. Tin, None; J. E. Pope, None; V. Bykerk, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/early-rheumatoid-arthritis-patientsin-the-worse-disease-trajectory-group-fail-to-achieve-improvement-in-physical-function
Abstract Number: 488
Six-Year Retention Rates with Abatacept Vs TNF Inhibitors in the Treatment of Rheumatoid Arthritis: Experience from the Real-World Rhumadata Clinical Database and Registry Denis Choquette 1, Louis Bessette2, Boulos Haraoui3, Jean-Pierre Raynauld1, Diane Sauvageau1, Angèle Turcotte4, Édith Villeneuve1 and Louis Coupal1, 1Rheumatology, Institut de recherche en rhumatologie de Montréal (IRRM), Montréal, QC, Canada, 2Centre d’Ostéoporose et de Rhumatologie de Québec (CORQ), Québec, QC, Canada, 3Université de Montréal, Montreal, QC, Canada, 4Rheumatology, Centre d’ostéoporose et de rhumatologie de Québec (CORQ), Québec, QC, Canada First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: The sustainability of any regimen is an important factor to consider when selecting therapy for chronic conditions, such as rheumatoid arthritis (RA). Recent reports suggest that patients (pts) treated with abatacept (ABA) might have better retention rates than those treated with anti-TNFs. We aim to further assess long term retention rates of ABA in comparison with anti-TNFs in the first and second lines of treatment in a real life setting using the Rhumadata database and clinical registry. Methods: RA patients treated at the Institut de recherche en Rhumatologie de Montréal (IRRM) and the Centre d'Ostéoporose et de Rhumatologie de Québec (CORQ) with either ABA or an anti-TNF inhibitor, adalimumab (ADA), etanercept (ETA), or infliximab (INF) as first biologic (first cohort) or second biologic (second cohort) after January 1st 2007. Descriptive statistics were used to describe patient characteristics. Characteristics were compared using ANOVA with Bonferroni correction. Kaplan-Meier methods were used to compute the cumulative incidence of treatment discontinuation. Results: The first cohort included 403 pts (62 ABA, 111 ADA, 195 ETA, and 35 INF) and the second cohort included 189 pts (76 ABA, 47 ADA, 47 ETA, and 19 INF). No clinically significant differences in baseline characteristics were noted between treatment groups. There were no significant differences in retention rates between ABA and anti-TNFs in the first cohort, Figure 1. The estimated 6-years drug retention rates were 52.3% (SD=8.4%) for ABA, 37.8% (SD=4.9%) for ADA, 43.6% (SD=4.3%) for ETA and 45.6% (SD=8.8%) for INF. In the second cohort, in patient with RA having failed a first anti-TNF agent, retention rates with ABA were significantly higher compared to anti-TNFs, Figure 2. For this cohort, the estimated 6-years drug retention rates were 41.2% (SD=7.4%) for ABA, 15.2%
(SD=6.3%) for ADA, 22.7% (SD=7.5%) for ETA and 33.1% (SD=13.1%) for INF. The significantly higher retention rates with ABA in the second cohort were maintained regardless of RF or anti-CCP status or whether the biologics were used as monotherapy or in combination with DMARDs. Lack of efficacy (40.1% and 57.3% in the first and second cohort, respectively) and adverse effects (13.9% and 12.2% in the first and second cohort, respectively) were the most commonly cited reasons for discontinuation. Conclusion: As a first line biologic, in patient with RA, ABA has similar 6-year retention rates as anti-TNFs. As a second line biologic, in patient with RA, ABA has significantly higher 6-years retention rates compared to anti-TNFs. Figure 1.
Disclosure: D. Choquette, AbbVie, Amgen, Celgene, Bristol-Myers Squibb, Janssen Pharmaceutical Product, L.P., Pfizer Inc, Roche, Novartis, UCB, Hospira, Sanofi, Merck, 5; L. Bessette, AbbVie, Amgen, Celgene, Bristol-Myers
Squibb, Janssen Pharmaceutical Product, L.P., Pfizer Inc, Roche, UCB, 5,AbbVie, Amgen, Celgene, Bristol-Myers Squibb, Janssen Pharmaceutical Product, L.P., Pfizer Inc, Roche, UCB, 2; B. Haraoui, Abbvie, Celgene, Amgen, BMS, Janssen, Pfizer, Roche and UCB Pharma, 2,Abbvie, Celgene, Amgen, BMS, Janssen, Pfizer, Roche and UCB Pharma, 5; J. P. Raynauld, None; D. Sauvageau, None; A. Turcotte, AbbVie, Amgen, Celgene, Bristol-Myers Squibb, Janssen Pharmaceutical Product, L.P., Pfizer Inc, Roche, UCB, Eli Lilly, 5; Villeneuve, AbbVie, Amgen, Bristol-Myers Squibb, 5; L. Coupal, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/six-year-retention-rates-withabatacept-vs-tnf-inhibitors-in-the-treatment-of-rheumatoid-arthritis-experience-from-the-real-world-rhumadataclinical-database-and-registry
Abstract Number: 489
Drug Survival and Toxicity of Methotrexate Monotherapy in Daily Clinical Practice. Results from an Early Arthritis Clinic Christian A. Waimann1,2, Margarita Landi3, Fernando Dal Pra3, Gustavo Citera4, Maria Celeste Orozco4, Osvaldo Luis Cerda3, Federico Ceccatto5, Sergio Paira5, Francisco Colombres6, Alberto Berman7, Horacio Berman7, Anastasia Secco8, Marta Mamani8, Maritza Manzano8, Maria Victoria Martire8, Francisco Caeiro9, Maria Haye Salinas10, Alejandro J. Alvarellos10, Ana C. Alvarez10, Javier Rosa11, Valeria Scaglioni12, Enrique R. Soriano11, Josefina Marcos13, Mercedes Argentina García14, AC Costi15, Alejandro Martinez16, Oscar Luis Rillo16, Edson Veloso17, Ricardo V. Juárez18, Maria Elena Crespo19, Ana Quinteros20, Doralia Vasquez20, C Ledesma21, Gabriela Salvatierra21, R Quintana22, Monica Sacnun23 and Marcelo Abdala24, 1Rheumatology, Hospital Dr. Hector Cura, Olavarria, Argentina, 2Rheumatology section, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 3Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 4Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 5Hospital Jose Maria Cullen, Santa Fe, Argentina, 6Tucuman, Centro Médico Privado de Reumatología, Tucumán, Argentina, 7Centro Médico Privado de Reumatología, Tucumán, Argentina, 8Rheumatology, Hospital Bernardino Rivadavia, Buenos Aires, Argentina, 9Reumatología, Hospital Privado de Córdoba, Córdoba, Argentina, 10Rheumatology, Hospital Privado de Córdoba, Córdoba, Argentina, 11Hospital Italiano, Buenos Aires, Argentina, 12Rheumatology, Hospital Italiano, Buenos Aires, Argentina, 13HIGA San Martín, La Plata, Argentina, 14Rheumatology Unit, HIGA San Martín, La Plata, Argentina, 15Rheumatology, HIGA San Martín, La Plata, Argentina, 16Rheumatology, Hospital General de Agudos “Dr. Ignacio Pirovano”, Buenos Aires, Argentina, 17Sanatorio y Universidad Adventista Del Plata, Entre Rios, Argentina, 18Rheumatology Section, Hospital Señor del Milagro, Salta, Argentina, 19Hospital Señor del Milagro, Salta, Argentina, 20Centro Integral De Reumatologia, Tucumán, Argentina, 21Instituto Provincial De Rehabilitación Integral, Santiago del Estero, Argentina, 22Rheumatology, Hosp. Provincial, Rosario, Argentina, 23Hosp. Provincial, Rosario, Argentina, 24Hospital Provincial del Centenario, Santa Fe, Argentina First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Several trials had reported the efficacy and toxicity of methotrexate monotherapy in patients with early rheumatoid arthritis. However, patients outside clinical trials could be more complex and heterogeneous,
with a wide range of comorbidities and clinical characteristics. The aim of our study was to estimate the drug survival and toxicity of methotrexate monotherapy in real life setting. Methods: We included a cohort of DMARDs naïve patients with diagnosis of early rheumatoid arthritis (RA) of less than 2 years of disease duration. Data was collected every 3 months, including sociodemographic characteristics, functional status, disease activity and medication (dose, treatment strategy and toxicity). The primary outcome was methotrexate monotherapy survival. Time to outcome was assessed from treatment initiation to the end of methotrexate monotherapy (drug suspension or addition of DMARDs/biologics) or last follow-up. Kaplan-Meier product limit method was used to estimate outcome probability. Cox proportional hazards models were fit to determine possible predictors of methotrexate monotherapy survival. A p-value of 0.05 was considered statistically significant. Results: We included 563 DMARDs (disease-modifying antirheumatic drugs) naive patients with early rheumatoid arthritis. Mean follow-up was 24 ± 16 months. Mean age was 51 ± 14 years, 82% were female and disease duration was 7 ± 6 months. Baseline DAS28 and HAQ were 4.0 ± 1.2 and 0.9 ± 0.6, respectively. Methotrexate (MTX) was the most frequently DMARD used [505 (90%)], followed by Leflunomide [LFN, 193 (34%)], Hydroxychloroquine [HCQ, 105 (19%)] and Sulfazalazine [SFZ, 22 (4%)]. When analyzing treatment strategy, first choice was Methotrexate monotherapy in 384 (68%) of the cases. MTX mean dose was 16 ± 4 mg/week and 44% used MTX doses higher or equal than 20 mg/week. One hundred and fifty patients (40%) had to stop methotrexate monotherapy, with a median survival of 26 months (failure rate = 0.027/patient-months of follow-up). Main reasons for suspension were as follow: addition or substitution of DMARs/biologics due to inefficacy (79%), adverse event (7%) and others (14%). On multivariate analysis, being younger, having a higher disease activity and initial concomitant treatment with prednisone ≥10mg/day, were associated with a higher methotrexate monotherapy survival (Table 1) Conclusion: In daily clinical practice, 4 out of 10 patients with early rheumatoid arthritis fail to methotrexate monotherapy, being inefficacy the main reason for discontinuation. Only 7% of patients had to stop treatment due to adverse events. Younger age, higher disease activity and initial combination with prednisone ≥10mg/day were associated with a higher methotrexate monotherapy survival. Table 1. Cox proportional hazard model HR p-value 95%CI% Male sex 0.958 0.856 0.605 1.518 Age (years) 0.985 0.018 0.972 0.997 Disease duration (months) 1.008 0.631 0.976 1.041 Baseline DAS28 1.155 0.033 1.012 1.319 Time to first DMAR 0.999 0.724 0.997 1.002 (months) Methotrexate initial dose 1.016 0.585 0.960 1.075 (mg/week) Mean initial dose of prednisone 10, with data collected at routine clinic visits. At each visit, we collect standard RA assessments, including joint counts, RAPID3, and CDAI scores. Patients complete a PROMIS assessment quantifying their health status in 5 domains: pain, fatigue, depression, physical function, and social function. Patients are also asked to select priority targets, consisting of 5 items from the domain they deem most important; answers to these questions are also collected at each visit. Table 1 shows the demographics, clinical status and PROMIS measures for the first 94 patients enrolled. Results: Compared to the US general population reference values for PROMIS (m=50; SD=10), patients had worse fatigue (m=56.7), pain (m=57.7), and physical function (m=42.3). Baseline scores on depression and social functioning were close to the average of the general US population. Patients with CDAI > 10 scored worse across all domains than those with CDAI ≤ 10. When selecting prioritization areas for treatment targets, 38% of patients selected physical function, followed by 35% of participants selecting pain, 16% selecting fatigue, 6% selecting depression, and 4% selecting social function; those with active disease were much more likely to select pain (45% vs. 18%). Conclusion: Pain, physical function, and fatigue, the 3 domains in which patients reported worse health status than the general population, were also the areas most frequently selected by patients as priority targets for treatment. Physicians are
informed of the PROMIS scores at each visit, and we will track their impressions of the impact of these data on their treatment decisions. We will also explore, at a patient level, the correlation between PROMIS scores and standard disease activity measures Table 1 CDAI ≤ 10 CDAI > 10 (n=45)* Mean Age Female (n, %) College or Professional Degree (n, %) Employed (n, %) Smoker (n, %) PROMIS Pain (mean) PROMIS Fatigue (mean) PROMIS Depression (mean) PROMIS Physical Function (mean) PROMIS Social Function (mean)
42 (93%) 40 (95%) 35 (78%) 30 (71%) 31 (69%) 25 (60%) 4 (9%) 2 (5%) 53.6 62.1 53.1 59.8 49.2 53.8 45.2 39.4 50.0 44.7
All (n=94) 53.2 89 (95%) 69 (73%) 58 (62%) 6 (6%) 57.7 56.7 51.4 42.3 47.4
*Baseline CDAI not recorded in 7 patients Disclosure: E. M. Ruderman, Amgen, AbbVie, Corrona, Eli Lilly, Janssen, Novartis and Pfizer, 5; J. Beaumont, None; A. Muftic, None; A. M. Mandelin II, AbbVie, 8,Genentech., 8,Pfizer Inc, 8,UCB, 8; A. Eisenstein, None; G. J. Greene, None; D. Cella, AbbVie, 5,Pfizer Inc, 5,Boehringer Ingelheim, 5,Novartis Pharmaceutical Corporation, 5. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/personalizing-the-treat-to-targetapproach-in-rheumatoid-arthritis
Abstract Number: 491
A Paradigm Shift in the Disease Assessment of Rheumatoid Arthritis : From Blood to Urine Testing Wan-Uk Kim1, Yune-Jung Park2, Seung-Ah Yoo3, Bong Ki Hong3, Gi myo Kim4, Susanna Choi5, Saseong Lee3 and Chul-Soo Cho6, 1Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea, 2Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, South Korea, 3Institute of Bone and Joint Diseases, The Catholic University of Korea, Seoul, South Korea, 4Institute of bone and joint diseases, Catholic university, seoul, South Korea, 5Institute of Bone and Joint diseases, The Catholic University of Korea, seoul, South Korea, 6Internal Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor disease activity on a daily basis such as glucose measurement since RA activity fluctuates over time. Urine can be collected routinely at
home by patients themselves and tested for systemic inflammation. Recently, we had identified 4 urinary biomarker candidates-- gelsolin (GSN), orosomucoid (ORM)1, ORM2, and soluble CD14 (sCD14)-- in RA patients through transcriptomics and proteomics studies. Methods: Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner, focusing on their role in predicting RA activity and providing prognosis. Urinary concentrations of the four proteins were determined by enzyme-linked immune-sorbent assay. RA activity and severity were determined by assessing disease activity score 28 and X-rays of hands and feet of patients, respectively. Results: Urinary ORM1, ORM2, and sCD14 levels were elevated in RA patients. They were positively correlated with the status of the disease activity. In particular, urine determinations of one or two biomarkers (e.g. ORM1+ORM2 or sCD14+ORM2) efficiently represented the presence of high RA activity without the need for blood markers. In parallel, a more rapid radiographic progression in three years was observed in patients with higher ORM2 levels. In multivariate analysis, urinary ORM2 level was an independent risk factor for RA progression. Combination of urinary ORM2 and serum C-reactive protein synergistically increased the predictability for radiographic progression (the adjusted odds ratio: 46·5). In vitro functional studies revealed that ORM2 was mainly produced by RA synoviocytes in the joints, directly contributing to proinflammatory responses. Conclusion: Our urinary biomarkers provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals. Disclosure: W. U. Kim, Korea Healthcare Technology R&D Project, National Research Foundation of Korea (NRF) funded by the Ministry of Education, 2; Y. J. Park, None; S. A. Yoo, None; B. K. Hong, None; G. M. Kim, None; S. Choi, None; S. Lee, None; C. S. Cho, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-paradigm-shift-in-the-diseaseassessment-of-rheumatoid-arthritis-from-blood-to-urine-testing
Abstract Number: 492
Correlations Between Clinical, Laboratory and Ultrasound Joint Examination in RA Patients Treated with Rituximab Andreea Borangiu1, Diana Mazilu1, Ioana Saulescu1, Evelina Iachim2, Laura Grosanu1, Cosmin Constantinescu1, Andra Balanescu1, Denisa Predeteanu1, Ruxandra Ionescu1 and Daniela Opris1, 1University of Medicine and Pharmacy “Carol Davila”, Department of Internal Medicine and Rheumatology “Sf. Maria” Hospital, Bucharest, Romania, 2Carol Davila Medicine and Pharmacy University, Bucharest, Romania First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Correct assessment to biologics in rheumatoid arthritis (RA) patients is extremely important regarding future patient management. There is still an open debate about the utility of joint ultrasound (US) parameters and the monitoring of the activity. Methods:
52 consecutive RA patients on stable RTX treatment administered each 6 months were evaluated. Clinical and US evaluation were performed by two independent assessors, the same day as all laboratory tests. The scanning technique and the settings of the machine (ESAOTE MY LAB70, 15MHz linear probe) were the same for all patients. Examinations were performed by a trained ultrasonographer blinded to all clinical evaluations. US of both hands (dorsal wrist, 2nd to 5th volar metacarpophalangeal and 2nd to 4th volar proximal interphalangeal) was done. All patients were separated in 2 groups according to calculated SDAI, patients having SDAI 2.6 and ≤4.5) to a stable MTX dose (15 - 25 mg/wk) were enrolled and received three infusions of TCZ (8 mg/kg) iv every 4 weeks + MTX. Patients achieving good or moderate EULAR response at week 12 (n = 65) were randomized into Group A (TCZ 8 mg/kg plus MTX) or Group B (TCZ 8 mg/kg plus MTX placebo). Every four weeks disease activity was estimated with DAS28 (Disease Activity Score with 28 joint counts), SDAI (Simplified Disease Activity Index), CDAI (Clinical Disease Activity Index) and RADAI-5 (Rheumatoid Arthritis Disease Activity Index 5). In both groups patients were assigned to the anti-CCP-positive or -negative group. Group A included 17 patients anti-CCP-positive and 13 patients anti-CCP-negative; Group B 19 patients anti-CCP-positive and 14 patients antiCCP-negative. Statistical comparisons analyzed three time points (week 0, baseline; week 12, end of therapy TCZ plus
MTX and week 24, end of TCZ plus MTX or TCZ plus MTX placebo). Results: In the anti-CCP-positive and the anti-CCP-negative group DAS28, CDAI, SDAI and RADAI-5 changed significantly (p4.4, 3. clinical indication for initiating adalimumab or etanercept treatment. The exclusion criteria were: 1. diagnosis of other connective tissue diseases, 2. diagnosis of chronic infection. We obtained complete medical history and physical exam, demographic information, medications and laboratory data. At baseline and 14 weeks after TNF inhibitor therapy, we assessed DAS28 ESR and measured serum levels of Th1-associated chemokines (CXCL9, 10, 11) and Th17-associated chemokine (CCL20) using commercial ELISA kits. Responders and non-responders were defined as patients who had good/moderate response and no response at week 14 by EULAR response criteria. Wilcoxon two sample test was performed to compare chemokine levels. Results: We assessed 16 RA patients who started either adalimumab or etanercept. Their baseline characteristics, summarized in Table 1, show no significant differences between responders (n=9) and non-responders (n=7). Responders showed a trend toward higher levels of baseline Th1 chemokines compared to non- responders (Fig 1). CXCL10 levels were significantly higher in responders (437 ± 354 vs 144 ± 45 pg/ml, p=0.04) while CXCL9 (2266 ± 1517 vs 1126 ± 452 pg/ml, p=0.16),and CXCL11 (887 ± 1114 vs 515 ± 853 pg/ml, p=0.25) differences did not reach statistical significance. There were significant correlations between CXCL9 and CXCL10 (r =0.61, p=0.01) and between CXCL9 and CXCL11 (r=0.66, p=0.01). CCL20 levels were lower in responders but were not significantly different (15.6 ± 12.0 vs 33.8 ± 41.8 pg/ml, p=0.63). Conclusion: Elevated baseline levels of Th1 cytokines including CXCL9, 10 and 11 appear to be associated with favorable responses to TNF inhibitors whereas Th17 chemokine, CCL20, may be associated with unfavorable responses. Table 1. Baseline characteristics of RA patients Responders Non-responders p value (n=9) (n=7) Age (years) 45.6 50.6 0.43 Gender (female %) 89
RF or CCP positivity (%)
DAS28 ESR ESR (mm) Concomitant MTX (%)
Figure 1. Baseline Th1 chemokine level in responders (R) and non-responders (NR)
Disclosure: B. K. Han, None; A. Bottaro, None; I. Kuzin, None; N. J. Olsen, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-t-helper-cell-1th1-and-t-helper-cell-17th17associated-chemokines-as-prognostic-biomarkers-for-tumor-necrosis-factor-tnf-inhibitor-therapy-in-rheumatoid-arthritis-ra
Abstract Number: 563
Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following Re-Treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis Paul Emery1, G Burmester2, VP Bykerk3, B Combe4, Daniel E. Furst5, M Maldonado6 and T. W. J. Huizinga7, 1University of Leeds, Leeds,
Paul Emery , G Burmester , VP Bykerk , B Combe , Daniel E. Furst , M Maldonado and T. W. J. Huizinga , University of Leeds, Leeds, United Kingdom, 2Charité – University Medicine Berlin, Berlin, Germany, 3Hospital for Special Surgery, New York, NY, 4Service d’ImmunoRheumatologie, Montpellier, France, 5Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 6Bristol-Myers Squibb, Princeton, NJ, 7Leiden University Medical Center, Leiden, Netherlands First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I Session Type: ACR Poster Session A Session Time: 9:00AM-11:00AM Background/Purpose: Assessing Very Early Rheumatoid arthritis Treatment (AVERT) was a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of abatacept (ABA) treatment in three phased periods: during treatment, following withdrawal of all therapies and during re-exposure. Here, we present data from the withdrawal and re-exposure periods. Methods: MTX-naïve, anti-cyclic citrullinated peptide 2-positive patients (pts) with early RA (active synovitis in ≥2 joints for ≥8 wks, DAS28 [CRP] ≥3.2 and onset of symptoms within ≤2 yrs) were initially randomized to 12 months of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy or MTX alone (treatment period). Pts with DAS28 (CRP) 50% of pediatric rheumatologists in the US and Canada (n=277 in 2011; n=177 in 2014 and 59% AMIGO participants). By 2014, 86% of fellows and 31% of junior faculty were AMIGO mentees. In 2011, fellows were substantially less likely than senior faculty to have mentoring outside the home institution. This difference resolved by 2014. By 2014, the proportion of fellows with outside mentors increased markedly in the domains of research, setting career goals, and achieving career goals (Figure 1). No change was observed in clinical or teaching domains. Overall, fellows but not junior faculty reported an increase in satisfaction with career mentoring between 2011 and 2014. Conclusion: The implementation of AMIGO was associated with improved access to mentoring beyond the home institution for fellows in pediatric rheumatology as well as an increase in satisfaction with career mentoring measureable at the level of the whole community. These findings support the efficacy of the subspecialty-wide AMIGO mentoring program, and suggest that AMIGO may serve as a model for mentoring programs in adult rheumatology and in other domains of medicine. Figure 1: Access to Mentoring in 2011 and in 2014
Disclosure: L. N. Moorthy, None; E. Muscal, None; M. Riebschleger, None; M. S. Klein-Gitelman, None; L. E. Nigrovic, None; K. A. Rouster-Stevens, None; P. J. Ferguson, None; B. A. Eberhard, None; H. I. Brunner, None; S. Prahalad, None; R. Schneider, None; P. A. Nigrovic, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/improvement-in-mentoring-associated-withimplementation-of-an-inter-institutional-mentoring-program-within-pediatric-rheumatology
Abstract Number: 1015
Contribution of TNF and Type I Interferon to the Development of Persistent PostInflammatory Mechanical Allodynia in Arthritic Mice Sarah Woller1, Cody Ocheltree2, Tony Yaksh1 and Maripat Corr2, 1Anesthesiology, UCSD, La Jolla, CA, 2Division of Rheumatology, Allergy, and Immunology, UCSD, La Jolla, CA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Pain: Basic Aspects Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Male C57Bl/6 (WT) mice develop transient inflammation in response to K/BxN serum transfer and show a corresponding pain state, which persists beyond the resolution of inflammation. The current studies first examined the role of spinal cytokines, specifically TNF and IFNβ in the transition to a persistent, post-inflammatory pain state, which is mediated through Toll-like receptor (TLR) 4 signaling. Importantly, the contribution of TLR4 to pain states has been found to differ between male and female animals. Thus, our second aim was to examine whether female WT mice respond similarly to K/BxN serum transfer, and to examine whether TLR4 signaling associated spinal cytokines were involved in the development of tactile allodynia (TA) in female animals. Methods: K/BxN sera (100μl) was injected into male and female WT, Tnf-/-, Tlr4-/-, and Ifnar1-/- mice on Days 0 and 2. Ankle width and withdrawal thresholds were examined over 28 days and then analyzed in the peak inflammatory (d3-10) and post-inflammatory (d13-18) phases. Spinal cords were collected from WT and Tlr4-/- arthritic mice and changes in gene expression were measured using qPCR. Results: We examined spinal cords for differences in TNF and IFNβ gene transcripts on day 10 post K/BxN serum transfer, relative to day 0. IFNβ transcripts decreased in WT mice (average fold change: 0.41) and were increased in Tlr4-/- mice (average fold change: 18.84). In contrast, TNF transcripts increased in WT mice (average fold change 1.33), and remained unchanged in Tlr4-/- mice (average fold change 0.96). Next, we assessed the development of TA in male Ifnar1-/- and Tnf-/- mice. The early, inflammatory phase of pain is attenuated in Ifnar1-/- mice (1.18g threshold relative to 0.5g in WT males, p < .05); however these mice develop persistent pain while the late phase of pain is reduced in Tnf-/- mice (1.29g threshold, relative to 0.74g in WT males, p < .05). Next, we examined female WT mice after K/BxN serum transfer. To our surprise, female mice developed an initial tactile allodynia that is indistinguishable from males (0.72g relative to 1.97g at baseline), but do not develop a persistent pain state (post-inflammatory threshold: 1.36g, p < .05). The behavioral phenotype of female WT mice resembled that of Tlr4-/- males, and we assessed whether similar cytokine signaling contributed to the K/BxN pain phenotype. Both female Ifnar1-/- and Tnf-/- mice were indistinguishable from their male counterparts in terms of both ankle inflammation and pain (p > .05). We then determined whether TNF and IFNβ transcripts change over
time (days 0, 3, 10, 18, and 28) by qPCR in male and female WT mice. Males showed a general increase in spinal TNF mRNA expression, and a decrease in IFNβ. Although the female mice also showed an increase in TNF transcripts, they had a transient decrease in IFNβ and then recovered to initial levels. Conclusion: These results show persistent pain in male WT animals is associated with differential modulation by TNF and type I IFN. Female WT animals, however, fail to develop persistent pain, and show a recovery of IFNβ transcription indicating that co-modulation is important to prevent the development of persistent, post-inflammatory TA. Disclosure: S. Woller, None; C. Ocheltree, None; T. Yaksh, None; M. Corr, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/contribution-of-tnf-and-type-i-interferon-to-thedevelopment-of-persistent-post-inflammatory-mechanical-allodynia-in-arthritic-mice
Abstract Number: 1016
Collagen Antibodies Induce Pain-like Behavior in Mice Independent of Inflammation and Complement Activation but Requires FcÎ³rs Gustaf Wigerblad1, Katalin Sandor1, Kutty Selva Nandakumar2, Rikard Holmdahl3 and Camilla Svensson1, 1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden, 2Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, 3Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Pain: Basic Aspects Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Collagen Antibody Induced Arthritis (CAIA) is an acute mouse model of rheumatoid arthritis (RA). It is induced by an intravenous injection of a cocktail of monoclonal antibodies (mAb) against collagen type II (CII), producing a transient inflammation that typically starts around day 6-9 and peaks around day 12-15. Interestingly, in our studies aimed at characterizing pain-like behavior in the CAIA model we found that the mice displayed clear signs of nociception prior to the onset of inflammation. Thus, the purpose of this study was to characterize the pre-RA phase from a pain perspective and to investigate what drives anti-CII antibody-induced nociception. Methods: Male B10.RIII, B10.Q, and B10.Q C5-/-mice were injected i.v. with 4 mg/mouse of anti-CII mAbs cocktail, isotype control IgG, CII Ab Fab fragments, EndoS-treated CII mAbs, or CIIF4 mAbs and monitored for 5 days. Arthritis was examined by visual scoring of the paws (0-60), histological examination (H&E), and gene expression (qPCR) analysis of the ankle joints. MMP activity in the paws was visualized using MMPsense680. Pain-like behavior was monitored by measuring mechanical hypersensitivity with von Frey filaments day 0-5 and locomotion parameters by Comprehensive Lab Animal Monitoring System the night between days 2-3. Mice were injected subcutaneously (s.c.) with a peptide inhibitor (PMX53, 3 mg/kg/day) of the receptor for complement component 5a (C5aR). Results: Over the 5 days after injection of anti-CII mAb cocktail, only minor visual signs of inflammation (score: 1 TNFi ‡Significant interaction between 3 ICD-9 codes for SLE and > 2 codes for acute renal disease all >30 days apart, following > 12 months with none of these codes). MAX data were linked by the Centers for Medicare and Medicaid Studies (CMS) to the US Renal Datasystem (USRDS) to identify ESRD onset and subsequent deaths. The index date was the date that the incident LN definition was met. We followed individuals in the linked dataset through 12/31/2006. Deaths were captured in MAX prior to ESRD and in USRDS after ESRD. We examined baseline sex differences in sociodemographics and SLE comorbidities in the 12 months prior to the index date. We used Fine and Gray proportional hazards models to determine the subdistribution hazard ratios (HR) for ESRD by sex, accounting for the competing risk of death. Multivariable Cox proportional hazards regression models were used to estimate HRs for death by sex. To test the proportional hazards assumption, we included an interaction term for sex and follow-up time. The interaction term was statistically significant in our ESRD model and we therefore stratified follow-up time at 2 years post-index date where survival curves diverged. Results: Of the 2576 Medicaid patients with incident LN, 230 (9%) were male. Mean age was 30 years (+16) among males and 34 years (+14) among females (p 2 years after incident LN. (Table). HR for death did not differ by sex. Conclusion: ESRD risk was comparable in both sexes within 2 years of LN onset, but higher among males thereafter. Mortality rates were similar in males and females. To our knowledge, this is one of the largest incident LN cohorts followed for long-term outcomes by sex. However, the relatively small number of males limits conclusions. Further study of LN outcomes by sex should be pursued.
Table. Hazard Ratios for Development of End-Stage Renal Disease (ESRD) and Death in Males vs. Females among Medicaid Patients with Incident Lupus Nephritis Outcome Hazard Ratio*** (95% CI) ESRD within < 2 years of Lupus Nephritis Onset* 0.94 (0.57, 1.56) ESRD > 2 years following Lupus Nephritis Onset* 2.87 (1.48, 5.24) Death following Lupus Nephritis Onset** 0.98 (0.63, 1.52) * Subdistribution proportional hazards models, accounting for the competing risk of death in ESRD models. As the interaction between sex and follow-up time was significant (p 0.03), we stratified follow-up at the 2 year mark (< 2 years vs. > 2 years after index date). **The interaction between sex and follow-up time was not significant for analyses of death ***Mutivariable model adjusted for age, sex, race/ethnicity, calendar year of LN onset, US region, zip code-based socioeconomic status (Ward MM, J Rheum, 2007) and SLE Comorbidity Index (Ward MM, J Rheum, 2000). Females = referent. Disclosure: A. R. Broder, None; C. H. Feldman, None; A. Kumthekar, None; M. Alevizos, None; H. Guan, None; M. Barbhaiya, None; K. H. Costenbader, Glaxo Smith Kline, Biogen, Pfizer, Merck, Genzyme-Sanofi, 5,Pfizer, Biogen, Glaxo-Smith Kline, 2,Cel-Sci Corp, Alkermes, Generex, 1. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/sex-differences-in-rates-of-end-stage-renal-diseaseand-death-among-medicaid-patients-with-incident-lupus-nephritis
Abstract Number: 1068
Assessment of 10-Year Risk of Myocardial Infarction or Stroke in SLE Michelle Petri1 and Laurence S Magder2, 1Johns Hopkins University School of Medicine, Baltimore, MD, 2University of Maryland School of Medicine, Baltimore, MD First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment II: Patient-Reported Measures, Outcomes and Reporting Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM B Background/Purpose: In 2013 the American College of Cardiology (ACC) and the American Heart Association (AHA) developed a new formula to estimate the 10-year risk of an adverse cardiovascular event based on traditional cardiovascular risk factors. In contrast to previous formulae, this new formula focused on risk of “hard“ events of myocardial infarction or stroke. Using a large cohort of patients with SLE, we derived a formula for estimating the 10-year risk of hard cardiovascular events (CVE) among patients with SLE based on both traditional and SLE-related risk factors, and compared our findings to the ACC/AHA risk estimates. Methods: This analysis is based on data from the Hopkins Lupus Cohort since 1987. A CVE was defined as the first occurrence of a stroke or myocardial infarction (MI). Patients who had a CVE prior to cohort entry or within the first two years of cohort participation were exluded from the analysis. There were 1513 patients included, 92% female, 54% Caucasian, 39% African-American, median age at baseline was 35 and median duration of follow-up was 8 years. To derive the score, risk factors were calculated based on variables measured in the first two years of cohort participation. Cox Proportional Hazards models were constructed to determine the variables that affected the risk of a subsequent CVE. Using the results, a formula to calculate the risk of a CVE within the next 10 years was derived. Results: 100 CVE were observed: 63 strokes, 36 MI, and 1 diagnosed with both stroke and MI. Table 1 shows the results of a multivariable Cox model used to estimate 10 year risk. Table 1: Association between predictors and risk of a CVD event among patients with SLE.
Age (per decade) Male (vs. female) Systolic Blood Pressure (per 10 mmHg)1 Cholesterol (per 25 mg/dl)1 Current Smoking Diabetes SLEDAI (per unit increase)1 History of Lupus Anticoagulant Low Mean C31
Hazard Ratio (95% CI) 1.3 (1.1, 1.5) 1.5 (0.8, 2.8) 1.3 (1.1, 1.6)
1.1 (1.0, 1.2)
1.6 1.5 1.1 2.2 1.8
0.055 0.12 0.028 0.0003 0.027
(1.0, 2.6) (0,9, 2.6) (1.0, 1.2) (1.4, 3.3) (1.1, 2.9)
0.0050 0.17 0.0010
1 Based on mean during the first two years of cohort participation.
Table 2 shows how the estimated 10-year risk for CVE based on this model compares to the risk from the ACC/AHA risk assessment tool for selected subgroups. Table 2: Estimated 10-year risk based on our formula, and the ACC/AHA formula for selected subgroups. Risk Profile Estimated 10- Estimated 10year risk based year risk based on our formula on 2013 ACC/AHA score1 White Woman, age 40, SBP=120 (treated), 2.6% 0.7% Chol=150, HDL=40, No other risk factors White Woman, age 60, SBP=120 (treated), 4.2% Chol=150, HDL=40, No other risk factors White Woman, age 60, SBP=120 (treated), 6.9% Chol=150, HDL=40, Mean SLEDAI=3, No other risk factors White Woman, age 60, SBP=120 (treated), 7.4% Chol=150, HDL=40, Low C3, No other risk factors White Woman, age 60, SBP=120 (treated), 9.1% Chol=150, HDL=40, Hx of Lupus Anticoagulant, No other risk factors
3.9% 3.9% 3.9% 3.9%
1 Calculated at http://tools.cardiosource.org/ASCVD-Risk-Estimator/
Conclusion: Patients with SLE are generally at increased risk for myocardial infarction or stroke, especially at younger ages. The ACC/AHA score underestimates the true risk. The excess risk is highest among those with low complement, lupus anticoagulant, or high levels of disease activity. Our risk assessment tool can be useful in guiding efforts to reduce traditional and SLE-related risk factors for “hard“ cardiovascular events among patients with SLE. Disclosure: M. Petri, None; L. S. Magder, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/assessment-of-10-year-risk-of-myocardial-infarctionor-stroke-in-sle
Abstract Number: 1069
Child’s HLA-DRB1 Genotype Increases Maternal Risk of Systemic Lupus Erythematosus: Results from the Mother-Child Immunogenetic Study in Autoimmunity Giovanna I. Cruz 1, Xiaorong Shao2, Hong L. Quach2, Janelle Noble3, Nikolaos Patsopoulos4, Michael Busch5, Darrell Triulzi6, Wendy
Giovanna I. Cruz , Xiaorong Shao , Hong L. Quach , Janelle Noble , Nikolaos Patsopoulos , Michael Busch , Darrell Triulzi , Wendy S.W. Wong7, Benjamin Solomon7, John Niederhuber7, Lindsey A. Criswell8 and Lisa F. Barcellos2, 1School of Public Health, University of California, Berkeley, Berkeley, CA, 2Genetic Epidemiology and Genomics Laboratory, University of California, Berkeley, Berkeley, CA, 3Children's Hospital Oakland Research Institute, Oakland, CA, 4Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, 5Blood Systems Research Institute, San Francisco, CA, 6Institute of Transfusion Medicine, University of Pittsburgh, Pittsburgh, PA, 7Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, VA, 8Rosalind Russell / Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, CA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Genetics, Gene Expression, and Epigenetics Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: SLE [MIM 152700] disproportionately affects women of reproductive age and pregnant patients are more likely to experience flares. Fetal microchimerism (FMC), or the persistence of a small population of cells in the mother, is a natural consequence of pregnancy. Risk of SLE is possibly increased through fetal HLA-antigen molecular mimicry. The causes of SLE are unknown but genetic and environmental factors, including Epstein-Barr virus (EBV) infection, are suspected. The strongest genetic association is with HLADRB1 alleles *03:01, *15:01, *08:01. We hypothesize that compared to controls, SLE cases are more likely to have children with a) DRB1-associated risk alleles and/or b) DRB1*04:01that encodes a homologous amino acid sequence to EBV. Methods: We investigated mother-child HLA relationships in 218 SLE and 349 control mothers (and their 881 children) from the MotherChild Immunogenetic Study (MCIS). The MCIS is a study with over 9,000 individuals: cases were recruited at UC San Francisco; controls were recruited from the Blood Centers of the Pacific, the Institute for Transfusion Medicine at the University of Pittsburgh, and from studies at the Inova Translational Medicine Institute (ITMI). Comprehensive MHC region SNP genotyping was conducted using the Illumina MHC, ImmunoChip, and 660K arrays for MCIS participants and whole genome sequencing for ITMI controls. Classical two-field HLA alleles were imputed using SNP2HLA. Clinical data were abstracted from medical records. We selected mothers of European ancestry using multidimensional scaling and ancestry informative markers to minimize any impact of population stratification. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SLE and having any children who carry DRB1 risk alleles or DRB1*04:01. Results: Initial findings reveal an increased risk of SLE among mothers with children who carry DRB1*15:01 (OR 2.26; 95% CI, 1.393.66) and *04:01 (OR 1.73; 95% CI, 1.14-2.64), both adjusted for maternal genotype. Furthermore, we observed a stronger association between children who carry DRB1*15:01and the SLE complication lupus nephritis compared to controls (OR 2.75; 95% CI, 1.12-6.76, n=383). Conclusion: These findings support the hypothesis that a child’s genotype influences a mother’s risk of disease, independent of the mother’s genotype. This is the first study to demonstrate an association between a child’s DRB1 genotype and risk of SLE in the mother. Disclosure: G. I. Cruz, None; X. Shao, None; H. L. Quach, None; J. Noble, None; N. Patsopoulos, None; M. Busch, None; D. Triulzi, None; W. S. W. Wong, None; B. Solomon, None; J. Niederhuber, None; L. A. Criswell, None; L. F. Barcellos, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/childs-hla-drb1-genotype-increases-maternal-risk-ofsystemic-lupus-erythematosus-results-from-the-mother-child-immunogenetic-study-in-autoimmunity
Abstract Number: 1070
CD 14(C-159T) Polymorphism and Soluble CD14 Are Associated with Increased Disease Activity and Nephritis in SLE Sarit sekhar Pattanaik1, Aditya kumar Panda2, Rashmi ranjan Sahoo1, Rina Tripathy3 and Bidyut kumar Das1, 1Medicine, SCB Medical College, Cuttack, India, 2Centre for Life science, Central University of Jharkand, Ranchi, India, 3Biochemistry, SCB Medical College, Cuttack, India First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015
Session Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Genetics, Gene Expression, and Epigenetics Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Cluster of differentiation 14 (CD14) plays an important role in innate immune system as a co-receptor in TLRs (2, 4, 7 and 9) signaling. Host innate receptor TLR7 and 9 recognizes nucleic acids as a ligand and produce type I IFN which is believed to be associated in the pathogenesis of SLE. TLR7 and 9 require CD14 for effective signaling, we hypothesized that CD14 polymorphism and soluble CD14 levels would correlate with disease susceptibility and disease activity in SLE. Methods: In a case control hospital based study, 130 female SLE patients fulfilling the ACR criteria and 140 age, sex matched healthy controls were enrolled. CD14 (C-159T) polymorphism was genotyped by PCR-RFLP. In 78 SLE patients and 46 healthy controls plasma sCD14, TNF-α, IFN-α levels were quantified by ELISA. Clinical, serological and other markers of disease activity (C3, C4 and antidsDNA) were measured by standard laboratory procedures. Results: Prevalence of mutant genotypes (CT and TT) and allele T were significantly higher in patients of SLE. Mutants (CT and TT) for CD14(C-159T) polymorphism were associated with higher plasma sCD14, IFN-α and TNF-α compared to wild type CC. Plasma sCD14 levels were significantly high in SLE patients compared to healthy controls (P53 ng/ml) were identified in 105/298 (35%) of the SSc patients. Patients with high and low CCL18 did not differ regarding demographics, SSc subtype or auto-antibody profile (Table 1). Analysis of ILD parameters showed that high CCL18 was associated with low Forced Vital Capacity (FVC) at baseline, decline in FVC across the observation period and lung fibrosis progression; expressed as annual fibrosis progression rate (Table 2). Multivariate analyses showed associations between CCL18, FVC decline and FVC 10%, no (%) FVC 15%, no (%)
Total SSc cohort (n=298)
94.7 (20.5) 4.3 (13.7) 76 (26.6) 53 (18.5) 68.2 (21.7) 8.4 (14.8) 85 (29.9)
96.6 (19.6) 2.4 (10.9) 36 (19.0) 25 (13.2) 71.4 (20.9) 8.0 (14.1) 54 (28.7)
91.2 (21.8) 8.0 (17.4) 40 (41.2) 28 (28.9) 62.0 (22.0) 9.1 (16.0) 31 (32.2)
0.031 0.004 0. Cross-sectional construct validity was assessed by calculating the correlations of PROMIS scores with the other disease measures at baseline and longitudinal construct validity was assessed by correlations of between-study visit differences in PROMIS scores with differences in other disease measures. Results: 604 study subjects came for 899 study visits. PROMIS assessments were completed at 796 (88%) of the visits. The median
time to complete the set of PROMIS assessments was 8.7 minutes (IQR 6.1-12.1) for the total cohort, 15.2 minutes (IQR 11.9-19.2) for those older than 80, and 6.7 (IQR 4.9-9.6, )) minutes for those younger than 40. Mean PROMIS scores at baseline are shown in Table 1. PROMIS instruments correlated cross-sectionally with the individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. Weaker correlations were observed in differences of scores longitudinally. The differences in all PROMIS scores during active disease vs. remission were in the expected direction for each domain (Table 2). Conclusion: PROMIS measures have cross-sectional construct validity and help discriminate between active disease and remission. Inclusion of PROMIS instruments in disease assessment in vasculitis would enhance capture of patients' perspectives of disease burden and complement traditional physician-based outcome measures.
Disclosure: G. Tomasson, None; J. T. Farrar, None; D. Cuthbertson, None; C. McAlear, None; S. Asdown, None; D. Gebhart, None; G. Lanier, None; N. Milman, None; J. Peck, None; J. Robson, None; S. Carette, None; G. S. Hoffman, None; N. A. Khalidi, None; C. L. Koening, None; C. A. Langford, None; L. W. Moreland, None; P. A. Monach, None; C. Pagnoux, None; U. Specks, None; A. G. Sreih, None; S. R. Ytterberg, None; P. A. Merkel, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/administration-of-patient-reported-outcomemeasurement-information-system-promis-instruments-by-computer-adaptive-testing-in-patients-with-systemic-vasculitis
Abstract Number: 1082
ANCA-Negative and Myeloperoxidase-ANCA-Positive Patients with Granulomatosis with Polyangiitis: Clinical Manifestations and Risk of Relapse Eli Miloslavsky1, Na Lu2, Sebastian Unizony3, Hyon K. Choi3, Peter A. Merkel4, Philip Seo5, Robert F. Spiera6, Carol A. Langford7, Gary S. Hoffman7, Cees Kallenberg8, E. William St.Clair9, Nadia Tchao10, Fernando Fervenza11, Paul A. Monach12, Ulrich Specks13 and John H. Stone14, 1Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, 2Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 4Penn Vasculitis Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, 5Division of Rheumatology, Johns Hopkins, Baltimore, MD, 6Rheumatology, Hospital for Special Surgery, New York, NY, 7Rheumatology, Cleveland Clinic, Cleveland, OH, 8Rheumatology/Clin Immunol AA21, Univer Med Center Groningen, Groningen, Netherlands, 9Rheumatology and Immunology, Duke University, Durham, NC, 10ITN, San Francisco, CA, 11Mayo Clinic, Rochester, MN, 12Rheumatology, Boston University School of Medicine, Boston, MA, 13Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN, 14Massachusetts General Hospital
Rheumatology Unit, Harvard Medical School, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: Vasculitis I Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Recent studies in ANCA-associated vasculitis (AAV) have suggested that classification based on ANCA type (PR3 versus MPO) may represent a more clinically relevant division than the traditional disease type categorization (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). The differences between these two classifications are driven primarily by patients with GPA who are MPO-ANCA+ or ANCA-negative. However, little scrutiny of these patient subsets has been described in the literature. We analyzed the clinical features and treatment outcomes of MPO-ANCA+ patients with GPA and ANCA-negative patients with GPA enrolled in the Wegener’s Granlomatosis Etanercept Trial (WGET) or the Rituximab in AAV (RAVE) trial. Methods: We performed a pooled analysis of patients enrolled in the WGET and RAVE trials. We compared both MPO-ANCA+ and ANCAnegative patients with GPA to two well-defined AAV subgroups: 1) PR3-ANCA+ patients with GPA and, 2) MPO-ANCA+ patients with MPA. Results: Among the 365 patients analyzed, 273 had PR3-ANCA+ GPA (75%), 33 had MPO-ANCA+ GPA (9%), 15 had ANCA-negative GPA (4%) and 44 had MPO-ANCA+ MPA (12%). MPO-ANCA+ patients with GPA MPO-ANCA+ patients with GPA were more often female than PR3-ANCA+ patients with GPA and were younger than MPO-ANCA+ patients with MPA (Table 1). The clinical features and frequency of granulomatous inflammation confirmed by histopathology were similar between MPO-ANCA+ GPA and PR3-ANCA+ patients with GPA. However, MPO-ANCA+ patients with GPA showed a complete absence of scleritis and endobronchial lesions though these differences did not reach significance. MPO-ANCA+ patients with GPA also differed from MPO-ANCA+ patients with MPA in having more frequent manifestations typically associated with GPA. The rate of relapsing disease at trial entry and relapse rate during the trial in patients with MPO-ANCA+ GPA was similar to that of PR3-ANCA+ GPA but higher than MPO-ANCA+ patients with MPA.
ANCA-negative patients with GPA ANCA-negative patients with GPA were similar in age and sex distribution to PR3-ANCA+ patients with GPA but had lower BVAS/WG scores at trial entry (4.5 vs 7.7, p140 µmol/L, proteinuria >1 g/24 h, specific gastrointestinal, cardiomyopathy and CNS involvement). However, more than a third of them relapse, mainly during the first 2 years after treatment onset. This study aimed to determine whether combined GC and azathioprine (AZA) could achieve higher remission and lower relapse rates than GC alone in patients with newly diagnosed eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN), without increasing adverse events. Methods: All patients included in this multicenter, prospective, randomized, double-blind trial received GC, initially 1 mg/kg/day, then gradually tapered over 12 months (asthmatic patients’ doses were lowered as much as possible while controlling asthma symptoms) and were randomly assigned to receive concomitant 12 months of oral AZA (2 mg/kg/day, increased after 3 months to 3 mg/kg/day for insufficient responses, defined as BVAS >6, persistently elevated acute-phase reactants, eosinophilia >1x109/L or manifestations, with FFS always 0) or placebo. Patients were followed for another 12 months, for 24 months of follow-up. The primary endpoint was combined remission-induction failures and minor or major relapses at month (M) 24. Analyses used a modified intent-to-treat strategy and were adjusted according to the vasculitis. Results: Among the 101 eligible patients, 95(51 EGPA, 25 MPA, 19 PAN) met the inclusion criteria and received at least 1 dose of AZA (n=46) or placebo (n=49). At endpoint, 21 (45.6%) AZA-arm patients had remission-treatment failures and/or relapses compared to 24 (49.0%) placebo recipients (odds ratio [OR], 0.96; [95% CI, 0.41–2.24]). Secondary endpoints were also comparable between arms: initial remission rate (80.4% vs. 81.6%; OR, 0.90 [0.31–2.70]) and numbers of patients with minor (26.7% vs. 25.0%) or major relapses (13.3% vs. 10.4%) (OR, 1.45 [0.61–3.44]). Two (4.1%) AZA-arm patients died (1 sudden death at M12 while in complete remission, 1 86-year-old died of congestive heart failure). Mean and cumulative GC doses and area under the curve for GC use were also comparable between arms. At least 1 serious treatment-related adverse event occurred in 8 (17.4%) AZA-arm and 3 (6.1%) placebo-arm patients (OR, 3.22 [0.69-14.29]). For EGPA patients, neither the primary endpoint nor the numbers with exacerbated asthma/rhinosinusal disease differed between arms. Conclusion: At study M24, AZA adjunction to GC induction did not lower the absolute risk of treatment failure or relapse in patients with non-severe SNVs, compared to GC alone, had no steroid-sparing effect, and, did not reduce EGPA patients’ rate of asthma/rhinosinusal disease exacerbations (CHUSPAN2 trial was funded by French Ministry of Health PHRC P060243 and sponsored by AP–HP; ClinicalTrials.gov number, NCT00647166). Disclosure: X. Puéchal, None; C. Pagnoux, None; G. Baron, None; T. Quémeneur, None; A. Néel, None; C. Agard, None; F. Lifermann, None; E. Liozon, None; M. Ruivard, None; P. Godmer, None; N. Limal, None; A. Mékinian, None; T. Papo, None; A. M. Ruppert, None; A. Bourgarit-Durand, None; B. Bienvenu, None; L. Geffray, None; J. L. Saraux, None; E. Diot, None; B. Crestani, None; X. Delbrel, None; L. Sailler, None; P. Cohen, None; V. Le Guern, None; B. Terrier, None; M. Groh, None; C. Le Jeunne, None; L. Mouthon, None; P. Ravaud, None; L. Guillevin for The French Vasculitis Study Group, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/does-adding-azathioprine-to-glucocorticoid-inductionincrease-the-remission-rate-and-prevent-relapses-in-patients-with-systemic-necrotizing-vasculitides-without-poor-prognosis-factors-amulticenter
Abstract Number: 1087
“It Was Just My Right Pace”: A Qualitative Study Exploring Yoga Practice in Adults with Rheumatoid Arthritis Heather Greysen, School of Nursing, University of California San Francisco, San Francisco, CA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: ACR/ARHP Combined Abstract Session: Rehabilitation Session Type: ACR/ARHP Combined Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Physical activity is reported to improve physical function and reduce disease symptoms in adults with rheumatoid arthritis (RA); however adults with RA are less likely to participate in physical activity than adults with other chronic diseases. The dynamic mind-body physical activity of yoga may be an acceptable and beneficial way for RA adults to increase physical activity. However, little is known about how patients with RA are practicing yoga in the community and about the benefits they experience. The objective of this qualitative study was to explore yoga practice characteristics in addition to perceived benefits and facilitators of yoga practice in adults with RA. Methods: A convenience sample of 17 adults, with rheumatologist-diagnosed RA, who had participated in yoga within the previous year, completed a semi-structured telephone interview. An interview guide was used to explore: the decision to start, continue and stop yoga; perceived benefits of yoga; importance of components of a yoga session; and general thoughts about yoga as it relates to RA. Thematic analysis was used to analyze interview transcripts. Results: The majority of the 17 participants were white (71%), female (94%), employed full-time (53%), had mean age of 56 years, had an average disease duration of 21 years, and had bachelor’s or graduate degrees (65%). The primary style of yoga practiced was Vinyasa and Restorative/Gentle (47% combined). Four main themes were identified: (1) Facilitators, (2) Barriers, (3) Benefits, and (4) Harms of yoga practice. Facilitators included: socialization, physical fitness, and improving practice. Barriers included: finances and class mismatch. Benefits included: increased coping abilities and improved sleep, flexibility, energy, strength, balance, pain, mood, and physical function. Harms included RA flares and muscle strain injuries. There were many styles of yoga practiced and participants described various ways to adapt or change an existing yoga practice to meet the physical and emotional needs of the practitioner on any particular day. Study participant quotes illustrated how the dynamic exercise of yoga, which can be gentle with breath exercises, meditation, and relaxing stretches or can be a vigorous exercise with fast moving strenuous poses, suited their dynamic needs as a person with fluctuating symptom burden. Conclusion: In this study RA patients described how yoga practice helped improve physical function and numerous RA disease symptoms. Yoga practice can provide many benefits for adults with RA when it is practiced at the right pace for the individual. Yoga practices vary and yoga may not be beneficial for every adult with RA, in fact it may be harmful if practiced inappropriately. Next steps include further investigating the role of the yoga teacher and the physical yoga practice environment as facilitators and barriers to practice.
Table 1. Main Themes and corresponding yoga participant quotes Key Theme SubTheme Quote Facilitators Desire for physical fitness “… I thought that it would help me stretch out and um, hopefully give me more mobility.” Being influenced by others “…the Pain Management Program, they suggested that I get into yoga” Increased benefits
Financial issues Yoga class mismatches
Physical and mental
Pride and achievement A tool to cope Harms
“…my friends said, ‘why don’t you give it a try’” "in the beginning, my joint stuff was really bad, it was kind of hard for me to do all the poses, but as I started doing it, I did notice that there were certain poses like the triangle pose, and stuff, that, I hated at one point, but then I was able to do it, so I noticed that my flexibility did improve." "She recommends that I have it twice a week, but financially I just can't do that." “I think I would like to try yoga again but it would have to be in a therapeutic environment, meaning, I would need, probably pillows or other things that would help me to do the exercises, you know.” “it just helps me with my overall mobility, I just feel like I am able to move so much better...I have improvement in all of those things, pain, energy, mood…I really, really like it, I feel it's so worth it, I do enjoy it very much.” “Well, it just made me feel better, more flexible, it made me feel, um, more calm, more better inside, stronger….it helps my mood, outlook and energy” “It was, the fellowship, the people. You know, you get hear somebody else griping about their toes hurting and their elbow hurtin, and then you know, we all get in there and we start doing our exercises and stuff and then we're talking about grandkids, you know, catchin crab or salmon and we start talkin about other stuff instead of you know, whatever hurts, so that part of it is a big uplift.” “I was pretty proud of myself for getting through it…when I do certain moves, I can feel pretty good about myself” “I think the breathing and the meditation are a big part …it's just, when you have RA you can get a lot of negative thinking and this really helps with that…yoga is really helpful, like a tool to turn to.” “I had to stop doing yoga because of my RA. I needed something more gentle, so I do Qigong now. I actually tried yoga again recently, but it caused a flare, so I said, okay, well, I’ve got to stop doing that.”
Disclosure: H. Greysen, None; View Abstract and Citation Information Online - http://acrabstracts.org/abstract/it-was-just-my-right-pace-a-qualitative-studyexploring-yoga-practice-in-adults-with-rheumatoid-arthritis Abstract Number: 1088
Effect of Training on Knee Torsional Stiffness and Its Relationship to Tibial Compressive and Anterior Shear Forces in Recreational Female Runners Bhushan Thakkar1 and D. S. Blaise Williams III2, 1PHYSICAL THERAPY, VIRGINIA COMMONWEALTH UNIVERSITY, RICHMOND, VA, 2Physical Therapy, Virginia Commonwealth University, Richmond, VA First publication: September 29, 2015 SESSION INFORMATION Session Date: Sunday, November 8, 2015 Session Title: ACR/ARHP Combined Abstract Session: Rehabilitation Session Type: ACR/ARHP Combined Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: 42 million Americans participate annually in running. In 2014, the half marathon was the most popular distance with a total of 61% females (1.2 million) finishing these races. Further, there has been a 2% increase annually in new female runners
completing a half marathon. Because medial knee osteoarthritis (MOA) is more prevalent among women, it is reasonable to investigate the mechanical impact of females training for a half marathon. Knee stiffness is related to leg stiffness which is significantly greater in individuals with MOA during walking. However, it is currently unknown how knee mechanics may be impacted by running and training for a half marathon distance. Therefore, the purpose of this study is to determine the relationship between shear and compressive forces and torsional stiffness at the knee with training. Methods: A 16 week half-marathon training program was completed. Pre- and post-training analyses were completed. 3D gait analysis was performed during a 30-second treadmill run at self-selected pace. Retroreflective markers were placed on bilateral lower extremities. Kinematic data were collected at 240 Hz with a 5-camera motion analysis system. Commercial software was used to reconstruct 3-D coordinates for each marker and generate kinematic and kinetic variables. Torsional stiffness was calculated as the slope between the net joint moment and the angular displacement at the knee joint in the sagittal plane. Univariate regression analyses were calculated for stiffness and shear, stiffness and compression (pre and post). Welch 2 sample t tests were used to compare pre and post stiffness and pre and post shear. Results: 21 female recreational runners between 33-56 years. (µ=47.6±8.1 yrs).There were significant differences found between pre and post stiffness (p= 0.03), pre and post compression (p=0.01), pre and post joint moment (p=0.04) and pre and post stride frequency (p=0.02). Regression models predicted a significant relationship between joint moment and shear (pre) (p=485,000 sites was performed using Illumina HumanMethylation450 arrays; differential methylation was defined as FDR-corrected p5 on a 10 point scale. Participants also completed pre- and post-curriculum questionnaires containing subjective (comfort and confidence) and objective (knowledge) domains. Content knowledge was assessed using validated questions in the literature, many of which had an orthopedic focus. Results: Of the 8 fellows who participated in the program, 75% reported no prior formal MSKE training. All participants felt that training in the MSKE should be part of fellowship and over 80% of fellows were likely or extremely like to recommend the course to others. The
average rating of the curriculum was 8/10. The post-curriculum assessment showed: 1) modest increase in the percentage of fellows endorsing comfort in their exam skills and confidence in their ability to assess disease activity; 2) decrease in the percentage of participants endorsing confidence in diagnosing MSK pathology (Figure 1a); 3) slight improvement in objective scores (Figure 1b).Over 60% of participants felt they could benefit from more practice time. Conclusion: We successfully implemented a structured MSKE curriculum that was received with enthusiasm and engagement among participants as reflected in their overall rating of the program. The modest improvement in both subjective and objective components of the post course assessment questionnaire may have been due to limitations of the questionnaire. The decline in the participants' confidence in diagnosing MSK pathology may reflect fellows' heightened awareness of limitations in their knowledge at the end of the curriculum. An observed structured clinical assessment may more effectively measure skills relevant to rheumatology and thus improve trainees' confidence.
Disclosure: S. Narain, None; S. Kasturi, None; V. Bykerk, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comprehensive-musculoskeletal-exam-curriculum-forrheumatology-fellows
Abstract Number: 1188
Comprehensive Musculoskeletal Course Improves Post-Graduate Trainees’ Confidence in Performing Joint Injections Erica Jaffe 1, Andrea M. Barker2, Grant W. Cannon3, J. Peter Beck4 and Michael J. Battistone5, 1Internal Medicine, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 2General Internal Medicine, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 3Division of Rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 4Orthopaedics, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 5Rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster I Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Developing confidence in procedural skills is an important aspect in improving procedural competency. Although a number of studies have explored effective methods to teach arthrocentesis, the relationship between the number of injections performed and confidence in injection skills has not been researched. We investigated the number of subacromial (SA) and knee injections required for a learner to become confident in procedural skills. Methods: Internal Medicine (IM) interns at our program participate in a week-long musculoskeletal skills course that takes place at a VA Medical Center. The course is open to post-graduate residents of other specialties. During the course SA and knee injection techniques are introduced through didactics and reinforced through simulation, peer-teaching and supervised ambulatory experiences. A total of 45 trainees participated in the course in 2014-15 (IM (32), physical medicine & rehabilitation (6), occupational medicine (5), orthopedics (2)). The number of SA and knee injections performed by each trainee was tallied. Before and after the course participants used a 5-point
Likert scale to rate confidence in performing joint injections. Data were divided into two categories for analysis (1-4 = less confident, 5 = highly confident). Chi squared analysis was used to compare the number of injections performed versus post-course self-assessment of confidence. Results: In addition to simulator training, trainees performed an average of 1.1 SA injections (range 0-3, median 1) and 1.6 knee injections (range 0-5, median 2). Mean confidence scores markedly increased from 2.4 pre-course to 4.5 post-course for SA injections and from 2.7 to 4.3 for knee injections. Of the participants who started as less confident in SA injections, only 1 (2%) decreased in confidence; 5 (11%) did not change. Of the participants who started as less confident in knee injections, only 1 (2%) decreased in confidence; 2 (4%) did not change. Table 1 shows association between the number of supervised joint injections performed and self-reported confidence post-course.
Conclusion: Our MSK course increased confidence in performing SA and knee injections. Participants who performed at least 2 SA injections had a statistically significant association with ranking themselves as highly confident post-course. There was no statistical significance association between the number of knee injections performed and self-assessment as highly confident post-course. Our next step will be confirming that the self-assessment of confidence is valid by comparing scores to external measures (e.g. objective structured clinical exam).
Disclosure: E. Jaffe, None; A. M. Barker, None; G. W. Cannon, None; J. P. Beck, None; M. J. Battistone, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/comprehensive-musculoskeletal-course-improves-postgraduate-trainees-confidence-in-performing-joint-injections
Abstract Number: 1189
Internal Medicine Subspecialty Fellows’ Attitudes Towards Teaching and Learning How to Teach: A Needs Assessment Eli Miloslavsky1 and Jakob McSparron2, 1Division of Rheumatology, Massachusetts General Hopsital, Boston, MA, 2Divsion of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster I Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM
Background/Purpose: Clinical fellows can have a major educational impact on students and residents. However, a number of barriers to teaching during inpatient consultation exist in the hospital environment, making it challenging to initiate teaching interactions, provide a positive environment for learning and deliver effective teaching. Improving fellows’ teaching skills has been proposed as a strategy to enhance teaching during consultation. Within Internal Medicine (IM) subspecialties, fellows’ attitudes towards teaching and interest in programs to improve teaching skills has been largely unexplored. We conducted a needs assessment to evaluate IM subspecialty fellows’ interest in teaching and improvement of their teaching skills. Methods: 379 IM subspecialty fellows from three academic medical centers (Massachusetts General Hospital, Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center) were invited to complete a survey assessing their attitudes towards teaching, assessment of barriers to teaching during consultation, interest in training related to teaching skills, and the current practices of assessment and improvement of teaching skills during fellowship. Results: 179 fellows from ten subspecialties responded to the survey (47% response rate), including 15 rheumatology fellows. 80% of fellows anticipate teaching during their careers, and 22% plan to participate in medical education scholarship (Table 1). Fellows reported a strong interest in teaching and programs aimed at improving their teaching skills (Table 2). Fellows who anticipated teaching during their career had more interest in teaching and teacher training. However, the majority of subjects (68%) reported no specific training focused on teaching skills during their fellowship and 37% have never received feedback about their teaching. Conclusion: Among a large sample of IM fellows participating in this study, the majority anticipate teaching during their careers. Fellows expressed a strong interest in programs aimed at improving their teaching skills. However, the majority of fellows did not have the opportunity to participate in such programs during fellowship and a significant minority reported that they did not receive feedback on their teaching. A need exists among fellows for programs focused on improving their teaching skills.
Disclosure: E. Miloslavsky, None; J. McSparron, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/internal-medicine-subspecialty-fellows-attitudestowards-teaching-and-learning-how-to-teach-a-needs-assessment
Abstract Number: 1190
Developing an Introductory Musculoskeletal Ultrasound Curriculum for Rheumatology Fellows Ekaterini Zapantis and Maria-Louise Barilla-LaBarca, Rheumatology, North Shore - Long Island Jewish Health System, Great Neck, NY First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster I Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM Background/Purpose: Musculoskeletal ultrasound has been increasingly recognized as a cost-effective, sensitive diagnostic bedside tool that rheumatologists can utilize across a wide spectrum of inflammatory and non-inflammatory diseases. It is rapidly becoming a highly requested elective during fellowship, though few curricular components exist for fellows not enrolled in a dedicated year-long course of training track. We report on our newly designed curriculum that features intermittent, short intense bursts of interactive teaching exercises that utilize formative assessment, flanking each session as a means to not only assess effectiveness of learning across several months, but also to reinforce important concepts from previous weeks and lead to a more durable retention of material when daily practice is not feasible. Methods: Six two-hour teaching sessions were developed over a four month period of time. Fellows personal goals were assessed initially to guide the curriculum development. Each session focused on a different joint area and consisted of a de-identified preassessment and cumulative assessment, short framing lecture, modeling of scanning technique, hands on scanning (with a 1:1 or 2:1 fellow:machine ratio), and post-assessment. All questions were reviewed with the fellows at the conclusion of every session. The cumulative assessment consisted of 10 multiple choice questions related to key concepts from prior sessions and the pre-assessment contained 5 multiple choice questions about the day's session. The post-test consisted of 5 multiple choice questions which covered the sessions's content. A final assessment was administered about a month after the last session which consisted of 53 multiple choice questions to assess retention of knowledge. Results: Three rheumatology fellows (two first years, one second year) with at most minimal experience, participated in the curriculum. Participants' personal goals included understanding the mechanics of ultrasound as well as identifying normal structures and pathology. A poll after the course revealed that all objectives were met. The average score of the six pre-assessments was 43.5% and 85% on the postassessments with an average percent improvement of 41.5%. The cumulative pre-assessments (not including the final assessment) average score was 71%. The final assessment average was 80%. It was observed that the fellows scored equally on first order and higher order questioning. Conclusion: Effective implementation of a musculoskeletal ultrasound curriculum can be easily introduced into a training program where routine daily practice is not possible. Intermittent, short intense bursts in coordination with spiraling content review, was shown to be a successful teaching method with fellows demonstrating durability of knowledge. Pre-Assessment Post Assessment Cumulative Average (%) Average (%) Assessment Average (%) Session One 58 81 (Introduction) Time zero Session Two
(Knee) 3 weeks Session Three
(Range: 70-90) 39
(Hand and Foot) 6 weeks Session Four
70 (Range: 50-90)
(Wrist) 7 weeks Session Five (Elbow) 10 weeks Session Six
(Range: 40-70) 56
80 (Range: 77-85)
14 weeks 43.5
Disclosure: E. Zapantis, None; M. L. Barilla-LaBarca, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/developing-an-introductory-musculoskeletalultrasound-curriculum-for-rheumatology-fellows
Abstract Number: 1191
Validity Evidence for Two Objective Structured Clinical Examination Stations to Assess Core Examination Skills of the Shoulder and Knee Michael J. Battistone 1, Andrea M. Barker2,3, J. Peter Beck4, Robert Z. Tashjian5 and Grant W. Cannon6, 1Rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 2General Internal Medicine, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 3Family and Preventative Medicine, University of Utah School of Medicine, Salt Lake City, UT, 4Orthopaedics, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT, 5Division of Orthopaedics, Salt Lake City VA and University of Utah, Salt Lake City, UT, 6Division of Rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City, UT First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster I Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Validity Evidence for 2 Objective Structured Clinical Examination Stations to Assess Core Examination Skills of the Shoulder and Knee Background/Purpose: A multi-disciplinary group developed two objective structured clinical examination (OSCE) stations to train and assess trainee's skills in the evaluation and management of shoulder pain and knee pain. Our objective was to examine the validity of these two OSCEs. Methods: Content Two orthopaedists, two rheumatologists, and a primary care provider developed checklists of physical exam maneuvers and criteria for guiding rater observations. Content was proposed by faculty, supplemented by literature review, and finalized through a modified Delphi process. Simulated cases representing common causes of shoulder pain and knee pain were constructed. Response Process A multi-disciplinary cohort of 69 trainees participated in the OSCEs in 2014-15. To promote accuracy of the simulated patient (SP) responses to assessment prompts, one faculty member served as SP and another as rater; ratings were recorded in real time. Internal Structure Two faculty members independently rated a portion of the cases. Percent agreement was calculated and Cohen's kappa corrected for chance agreement on binary outcomes. Relationship to Other Variables Relationship to self-assessment of ability to evaluate shoulder pain and knee pain was explored by written surveys utilizing a 5-point Likert scale. Responses were stratified into 3 categories – low, medium, and high – and compared with similarly stratified OSCE scores. Results: Checklists were developed for the shoulder (21 items) and knee (26 items); scoring rubrics converted each checklist to a 5-point scale. Using the examination approach in the checklists, trainees correctly identified rotator cuff pathology 61/69 (88%) and meniscal disease 62/69(89%) of the time. Inter-rater agreement was 89% for the knee (k = 0.55) and 96% for the shoulder (k = 0.51). Relationship of stratified self-assessment and OSCE scores is shown in Table 1; Pearson's coefficient indicated no correlation for either shoulder (0.02) or knee (-0.07). Table 1.
Conclusion: The two station OSCE is responsive and consistency in test performance across a range of trainees over time, with good inter-rater reliability. Lack of correlation with self-assessment suggests that these OSCEs measure a construct that is different than learners' self-confidence to support the continuing use of these two shoulder and knee OSCE stations in a structured educational program. The next steps will search for additional validity evidence of these experiences. Disclosure: M. J. Battistone, None; A. M. Barker, None; J. P. Beck, None; R. Z. Tashjian, None; G. W. Cannon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/validity-evidence-for-two-objective-structuredclinical-examination-stations-to-assess-core-examination-skills-of-the-shoulder-and-knee
Abstract Number: 1192
The F-Word: Why Is Talking about Fatigue so Hard? Ruth Hart1, Katie Hackett2, Julia Newton3, Wan-Fai Ng3,4 and Ben Thompson4,5, 1Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 3Newcastle University, Newcastle upon Tyne, United Kingdom, 4Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom, 5Newcastle University, Newcastle-upon-Tyne, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster (ARHP): Education/Community Programs Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Fatigue is a common symptom for people with inflammatory arthritis and associated auto-immune conditions. Its impact is wide-ranging and significantly reduces health-related quality of life. Research evidence, however, suggests that neither clinicians nor patients consistently raise the issue in clinic. In-depth discussion of fatigue and support from professionals to manage its impacts are rare. Arthritis Research UK developed a booklet, ‘Fatigue and Arthritis’, intended to help patients help themselves. Our study has explored patients’ approaches to managing fatigue and the impact this booklet has upon them. Methods: Twelve patients from a rheumatology outpatient service in north-east England took part in in-depth, qualitative interviews before and after being given the ‘Fatigue and Arthritis’ booklet. Patients were recruited purposively to ensure variation in diagnosis (rheumatoid arthritis (RA), ankylosing spondylitis (AS), and primary Sjögren’s Syndrome (pSS)), fatigue severity, and demographic characteristics. Data, in the form of transcripts, was analysed thematically using coding, mapping and memoing techniques. Results: This study confirms both the impact of fatigue and evidence that neither clinicians nor patients routinely raise the matter in consultations. Our data suggests patients face significant barriers to communicating their fatigue, including: reliance on a diverse, colloquial vocabulary to define the problem; uncertainty how it relates to their condition; doubts to its place on the consultation agenda; and a belief that nothing can be done about it. These barriers affect both if and how patients raise their concerns and are reinforced where clinicians’ responses do not invite elaboration. None of our participants, even those who had discussed fatigue with a clinician, reported having seen the ‘Fatigue and Arthritis’ booklet before. Not all found it of practical help in improving their day-to-day management and experience of fatigue (criticisms including the familiarity and/or unsuitability of advice). However, most reported gaining something from the booklet. Benefits included: improved understanding of a distressing symptom; validation of their concerns; and a sense that things could be done to manage fatigue. These gains made it easier to discuss fatigue and its impacts with clinicians and with family, friends and colleagues. Conclusion: Our research adds to the limited evidence on barriers to fatigue communication in the rheumatology clinic. In detailing patients’ difficulties, it reinforces prior recommendations that clinicians need to be prepared both to initiate discussions and respond sensitively to concerns about fatigue. It suggests that information materials such as the booklet featuring in this study may be a useful tool for improving communication. We encourage clinicians to give this booklet (or a similar resource) to patients reporting fatigue, and to commit to discussing it at future appointments. More effective communication about fatigue would improve clinicians’ understanding of the burden of disease individual patients bear and facilitate improved (shared) decision-making about management options. Disclosure: R. Hart, None; K. Hackett, None; J. Newton, None; W. F. Ng, None; B. Thompson, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-f-word-why-is-talking-about-fatigue-so-hard
Abstract Number: 1193
The Effectiveness of Low-Impact Exercise Program on Musculoskeletal Health of Asian Older Adults Huijuan Huang1, Titilayo Ologhobo1, Vicky Jin1, Sandra Goldsmith2 and Laura Robbins1, 1Education & Academic Affairs, Hospital for Special Surgery, New York, NY, 2Public and Patient Education, Hospital for Special Surgery, New York, NY First publication: September 29, 2015
SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Education Poster (ARHP): Education/Community Programs Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: The Center for Disease Control and Prevention (CDC) showed that in 2010-2015, 50% of adults 65 years or older reported an arthritis diagnosis. Studies have shown that participation in low-impact physical activity improves pain, function, mood and quality of life without worsening arthritis symptoms or disease severity. Despite this, the people with arthritis are less likely to be physically active. Nearly 44% of adults with arthritis report no leisure-time physical activity. In 2010, 25% of Asian seniors age 65 and older in NYC lived in poverty and were affected by musculoskeletal conditions. Asian women are at increased risk for developing osteoporosis since they tend to be slender with lower bone mass and avoid consuming dairy due to lactose intolerance. To help Asian seniors in underserved communities better manage musculoskeletal conditions, Hospital for Special Surgery developed its Asian Community Bone Health Initiative (ACBHI) in 2011. This study attempts to show that ACBHI improves musculoskeletal outcomes in Asian older adults. Methods: This eight week low-impact exercise program led by bilingual certified instructors, is held once a week in community-based organizations largely serving Asian older adults. Program impact was evaluated with a pre-post design using validated instruments to assess musculoskeletal outcomes. The 11-point Numeric Pain Rating Scale quantified the intensity of muscle or joint pain. Pain interference on seven daily activities was measured using the 11- point Brief Pain Inventory. The SF-36 measured physical function, while the 6-item selfefficacy scale for managing chronic disease was used to measure self-efficacy to exercise. Stiffness and fatigue levels were measured on an 11- point Numeric Rating Scale and 11- point Brief Fatigue Inventory respectively. Demographics such as age, gender and race/ethnicity were also collected. Paired t-test and chi square tests were used for statistical analysis. Results: Between 2011 and 2014, there were 311 participants in the exercise program; 175 responded to bilingual (English/Chinese) surveys. Respondents were mostly female (91%) between 65 and 84 years (75%). Physical function improved with a 69% increase in participants who could lift and carry groceries (p < 0.001); 88% increase in participants that could climb several flights of stairs (p < 0.001); 67% increase in participants who could bend, kneel, or stoop (p < 0.001). Participants’ muscle and joint pain decreased by 32% (p < 0.001). The mean pain intensity rating reduced from 5.6 to 4.4 (p < 0.001). Mean fatigue level dropped from 3.9 to 2.3 (p < 0.001) while the mean stiffness level also dropped from 3.8 to 2.6 (p < 0.001). Reductions in mean pain interference were seen in all seven daily activities. Participants reported that their exercise confidence increased from 6.9 to 8.5 (p 30 years of age experiencing hip or knee pain. The 15 question survey could be completed in less than five minutes and included: age; sex; language spoken at home; province/territory of residence and proximity of community/fitness centers; no/yes to pain, aching or discomfort in or around one or both knees/hips/shoulders, hands, neck, back on most days of the past three months; ever told you have arthritis; ever told you have OA or ‘wear and tear’ in your joints; ever had a hip or knee replacement surgery; membership at a community or fitness center; frequency of exercise at a center or at home; interest in attending a program twice a week for 6 weeks; and, amount willing to pay for such a program. We calculated descriptive statistics with 95% confidence intervals for all variables. Chi-square tests were used to evaluate factors that might be associated with willingness to pay. Results: After removing duplicate records, 751 completed the survey. 363 (51%) reported knee pain and 247 (34%) reported hip pain. Pain in other joints was reported by 482 (65%). Fifty-seven percent (423) reported that they had been told they had arthritis and 374 (51%) reported OA. Most respondents (79%) resided in British Columbia, 10% in Ontario, with the remainder in the other Canadian provinces. Those with hip or knee replacement surgery (73, 10%) were excluded from further analysis. The results were similar irrespective of joint for the remaining 408 likely to have hip and/or knee OA. Age ranged from 30 to >75 years with 260 (63.7%) aged 45 to 64 years. 86% were female. Only 2 (10 pack-years, and 8% were CCP/RF positive. Smoking >10 pack-years was associated with IJS at baseline (OR 1.59, 95% CI 1.09-2.32) and incident IJS at 2 years (OR 2.66, 95% CI 1.01-7.03). Current (OR 2.12, 95% CI 1.33-3.38) and past smokers (OR 1.61, 95% CI 1.12-2.33) had significantly higher odds of baseline IJS. BMI, education, sex/parity, GRS50, and RF/CCP were not associated with IJS at baseline or follow-up. Among those aged 10 pack-years had 4-fold increased odds of IJS (OR 4.39, 95% CI 2.22-8.66, Figure) compared to never smokers (p, interaction 0.02). Conclusion: In a high-risk cohort of first-degree relatives without RA, smoking was associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Those 10 pack-years had the highest risk of IJS with a significant interaction between smoking and age. Neither genetic nor serologic RA factors were significantly associated with IJS in this sample. These results suggest that smoking plays a role in inflammatory arthritis development. Longitudinal studies are needed to further investigate transitions of pre-clinical RA phases.
Disclosure: J. A. Sparks, None; S. C. Chang, None; K. D. Deane, None; R. W. Gan, None; K. Demoruelle, None; M. L. Feser, None; L. Moss, None; J. H. Buckner, None; R. M. Keating, None; K. H. Costenbader, Arthritis Care and Research, 5,International Journal of Clinical Practice, 5; P. K. Gregersen, Illumina Inc., 1,Janssen Pharmaceutica Product, L.P., 5,Biogen, Idec, 5; M. H. Weisman, None; T. R. Mikuls, None; J. R. O'Dell, None; V. M. Holers, Shared patent with Stanford University for use of biomarkers to predict clinical phenotypes in rheumatoid arthritis., 7; J. M. Norris, None; E. W. Karlson, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/genetic-environmental-and-serologic-risk-factors-forinflammatory-joint-signs-among-first-degree-relatives-without-rheumatoid-arthritis-in-a-prospective-cohort
Abstract Number: 1211
Shift of Rheumatoid Arthritis Onset Toward Old Age in Japan Based on a Nationwide Cohort Database Eri Kimura1, Tetsuji Sawada2, Koichiro Tahara1, Haeru Hayashi1, Mayu Tago1, Hiroaki Mori1, Toshihiro Matsui3, Jinju Nishino4 and Shigeto Tohma5, 1Rheumatology, Tokyo Medical University, Tokyo, Japan, 2Rheumatology, Tokyo Medical University, Shinjuku Tokyo, Japan, 3Department of Rheumatology, National Hospital Organization Sagamihara Hospital, Sagamihara, Kanagawa, Japan, 4Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan, 5Department of Rheumatology, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Previous studies from Western countries have demonstrated that the incidence of rheumatoid arthritis (RA) increases with age and the age of RA onset was about 59 years. However, in Japan, Imanka et al demonstrated that it increased from 37.5 years of age in the period of from 1960 to 1965 to 46.9 years of age in the period of from 1985 to 1990. Japan has faced a demographic change with a rapidly aging population in recent decades. In our experience in daily clinical practice over the past decade, we felt that we have encountered more patients who developed RA late in life than previously. In the present study, we aimed to determine whether there was a shift in the age of RA onset toward elderly onset based on a nationwide cohort database (National Database of Rheumatic Diseases by iR-net in Japan, NinJa) between 2003 and 2013. Methods: We analyzed the data of RA patients who were newly registered in the NinJa database as early RA (disease duration of less than 2 years) in 2003, 2008 and 2013. The numbers of patients who developed RA in 2002–2003, 2007–2008 and 2012–2013 were 536, 812 and 1,864, respectively. The age composition of the Japanese population in the corresponding periods was obtained from the database of the Ministry of Internal Affairs and Communications. Student's t-test was used to compare the average ages. Results: The average age of RA onset increased significantly over the past decade from 55.7 years in 2003 to 57.0 years and 59.9 years in 2008 and 2013, respectively. Regarding the distribution of the age of RA onset, the peak age shifted from the 50s in 2003 to the 60s in 2013 (Figure). There was no difference in the age of RA onset between male and female RA patients. It should also be noted that the
prevalence of RA was disproportionately higher in persons in their 50s in 2003, which included the so-called first baby boomers who were born after the world war, compared with persons in their 30s and 40s, even with consideration of the shift in age distribution of the general population. Conclusion: We have clearly demonstrated that the age of RA onset has significantly increased over the last decade in Japan. This may be attributed to the increase in the aging population, as a birth cohort effect. However, the smoking rate is higher among the first baby boomers than among persons of the following generations. Thus, in addition to the birth cohort effect, alteration of environmental factors, such as cigarette smoking, may contribute to the shift of age of RA onset in Japan.
Disclosure: E. Kimura, None; T. Sawada, None; K. Tahara, None; H. Hayashi, None; M. Tago, None; H. Mori, None; T. Matsui, None; J. Nishino, None; S. Tohma, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/shift-of-rheumatoid-arthritis-onset-toward-old-age-injapan-based-on-a-nationwide-cohort-database
Abstract Number: 1212
Investigation of Vitamin D Supplement Use, Rheumatoid Arthritis-Related Autoimmunity and Joint Signs Among Those at Increased Risk for the Development of Rheumatoid Arthritis Elizabeth A. Bemis1, Ryan W. Gan2, Marie L. Feser3, Michael H. Weisman4, James R. O'Dell5, Ted R. Mikuls5, Jane H. Buckner6, Peter K. Gregersen7, Richard M. Keating8, M. Kristen Demoruelle9, Kevin D. Deane10, V. Michael Holers11 and Jill M. Norris12, 1Epidemiology, Epidemiology, Colorado School of Public Health, Aurora, CO, 2Colorado School of Public Health, University of Colorado Denver, Aurora, CO, 3Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, 4Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, 5University of Nebraska Medical Center, Omaha, NE, 6Benaroya Research Institute at Virginia Mason, Seattle, WA, 7Feinstein Insititute for Medical Research, Manhasset, NY, 8Division of Rheumatology, Scripps Health, La Jolla, CA, 9Rheumatology, University of Colorado School of Medicine, Aurora, CO, 10Division of Rheumatology, U Colo Denver, Aurora, CO, 11Rheumatology Division, Univ of Colorado School of Med, Aurora, CO, 12University of Colorado Denver, Aurora, CO First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Vitamin D has immunomodulatory properties, and could be a protective factor against rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (anti-CCP) autoantibodies and swollen small joints of the hand (wrist and metacarpophalangeal [MCP] joints) are characteristics of RA that can be present years prior to the development of classifiable RA by established criteria. We investigated the associations between anti-CCP2 positivity and swollen joint symptoms with self-reported vitamin D supplement use in a population without RA, but at risk for development of RA. Methods: The multicenter Studies of the Etiology of RA (SERA) cohort study recruited subjects who are classified as RA-free at visit,
but at increased genetic and/or family risk for RA. At baseline, we assessed the association between self-reported vitamin D supplement use over the past year and presence of the two preclinical outcomes, anti-CCP2 positivity and having >= 1 swollen wrist and/or MCP joint. Three vitamin D exposure variables were created including a yes or no response, source of vitamin D (none, multivitamin or single supplement), and total months of use (0 months, 1-12 months or >12 months [i.e. those taking more than one vitamin D supplement]). These self-reported variables were found to be associated with 25-hydroxyvitamin D (25OHD) plasma concentrations that were available in a subset of the study population. Logistic regression models were used to estimate the independent association between the three exposure variables and the two outcomes, adjusting for age, sex, race, shared epitope, current smoking, cohort (first degree relative vs not), site of recruitment and use of other supplements. Results: The analysis cohort (n=2,383 at-risk subjects) was 69% female, 80% non-Hispanic white, with a mean age of 44.6 years. We identified 44 anti-CCP2 subjects and 57 subjects with >= 1 swollen joint at baseline. Vitamin D supplement use was not associated with anti-CCP2 positivity (Table). A marginally significant association was seen with joint signs, where those with >= 1 swollen joint were about half as likely to have been taking vitamin D supplements in the previous year (Table). Table: Odds ratios (OR) for anti-CCP2 positivity and >=1 swollen joint in relation to each vitamin D exposure variable. Outcome Anti-CCP2 >= 1 swollen joint* n=44 positive subjects OR (95% CI) 1.00 1.92 (0.47-7.92)
n=57 positive subjects OR (95% CI) p-value 1.00 Ref 0.47 (0.22-1.01) 0.07
Any Vitamin D Supplement p-value No Ref Yes 0.37 Vitamin D Source No vitamin D supplement 1.00 Ref 1.00 From a Multivitamin only 1.80 (0.43-7.55) 0.42 0.47 (0.22-1.04) From a Single supplement containing vitamin D 2.37 (0.49-11.43) 0.28 0.47 (0.17-1.32) Vitamin D Duration 0 Months (no vitamin D supplement) 1.00 Ref 1.00 1-12 Months 1.15 (0.26-5.05) 0.85 0.46 (0.22-1.05) >12 Months 2.45 (0.46-13.08) 0.29 0.45 (0.14-1.38) Adjusted for age, sex, race, cohort, recruitment site, current smoking status, Shared Epitope, and other supplement use.
Ref 0.08 0.19 Ref 0.07 0.16
*The sample size for the joint outcome analysis is n=1955, which is reduced because our off-site visits did not include a joint examination. Conclusion: Vitamin D supplement use was not associated with RA-related autoimmunity in at-risk subjects. An inverse trend between joint signs and vitamin D supplement use suggests the need for further research to examine the role of vitamin D in the later stages of preclinical RA. Disclosure: E. A. Bemis, None; R. W. Gan, None; M. L. Feser, None; M. H. Weisman, None; J. R. O'Dell, None; T. R. Mikuls, None; J. H. Buckner, None; P. K. Gregersen, Illumina Inc., 1,Janssen Pharmaceutica Product, L.P., 5,Biogen, Idec, 5; R. M. Keating, None; M. K. Demoruelle, None; K. D. Deane, None; V. M. Holers, Shared patent with Stanford University for use of biomarkers to predict clinical phenotypes in rheumatoid arthritis., 7; J. M. Norris, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/investigation-of-vitamin-d-supplement-use-rheumatoidarthritis-related-autoimmunity-and-joint-signs-among-those-at-increased-risk-for-the-development-of-rheumatoid-arthritis
Abstract Number: 1213
Prospective Study of Dietary Patterns and Risk of Rheumatoid Arthritis in Women Bing Lu1, Yang Hu2, Jeffrey A. Sparks3, Karen H. Costenbader4, Frank Hu5 and Elizabeth W. Karlson1, 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Nutrition, Harvard School of Public Health, Boston, MA, 3Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 4Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 5Harvard School of Public Health, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015
Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Although some individual dietary factors have been identified to be associated with the development of rheumatoid arthritis (RA), few studies have examined the effects of overall eating patterns on RA. We examined overall dietary patterns in relation to the risk of RA in a large prospective cohort, the Nurses’ Health Study II (NHSII). Methods: We prospectively followed 93,859 women free of RA at baseline who provided dietary data from 1991 to 2011 in the NHS II. Dietary data were obtained from validated food frequency questionnaires in 1991 and every 4 years during follow-up. Two dietary patterns were identified using principal component analysis: the Prudent dietary pattern characterized by high intakes of fruit, vegetables, legumes, whole grains, poultry, and fish; the Western pattern characterized by high intakes of red meats, processed meats, refined grains, French fries, desserts and sweets, and high-fat dairy products. The cumulative average pattern scores over time were categorized into quartiles. Incident RA cases were validated by medical record review. Time-varying Cox proportional hazards models were used to calculate hazard ratios (HR) after adjusting for age, census-track income, smoking, body mass index (BMI), total calories, alcohol use and physical activity. Results : During 1,509,033 person-years of follow-up, 626 incident cases of RA developed with the mean diagnosis age of 49. In the multivariable adjusted model, the Prudent pattern was associated with a reduced risk of RA, while the Western pattern was associated with an increased risk of RA (Table). The HRs (95% CI) across increasing quartiles of the Prudent pattern score were 1.00, 0.81(0.60,1.09),0.69(0.51,0.95), and 0.71(0.52,0.98) (p trend 0.04), and for the Western pattern, HRs ((95% CI) were 1.00, 1.41(1.01,1.98), 1.61(1.14,2.27), and 1.57(1.09,2.67) (p trend 0.03). After additional adjustment for BMI, the associations were attenuated. Conclusion: In this female cohort study, dietary patterns were association with RA risk. A negative association was found between a Prudent diet rich in fruit, vegetables, and fish, and the risk of RA, whereas a positive association was found between a Western diet rich in refined grains, processed and red meats, desserts, and French fries, and the risk of RA. Further analysis of BMI as a potential confounder or mediator of these associations is warranted. Table. Hazard ratios (95% CIs) of rheumatoid arthritis according to dietary pattern scores in the Nurses’ Health Study II (1991-2011)1 Dietary pattern scores (quartiles) p for Q1 Q2 Q3 Q4 trend2 Prudent Pattern Cases/ Person-years 93 / 368,986 84 / 379,428 77 / 382,024 87 / 378,595 Age-adjusted HR (95% CI) 1.00 0.81(0.60,1.09) 0.72(0.53,0.97) 0.78(0.58,1.05) 0.11 3 1.00 0.81(0.60,1.09) 0.69(0.51,0.95) 0.71(0.52,0.98) 0.04 Multivariable HR (95% CI) 1.00 0.82(0.60,1.10) 0.72(0.52,0.98) 0.74(0.54,1.02) 0.08 Multivariable HR (95% CI)4 Western Pattern Cases/ Person-years 60/371125 85/378,206 97/381,583 99/378,119 Age-adjusted HR (95% CI) 1.00 1.40(1.00,1.94) 1.60(1.16,2.21) 1.70(1.23,2.34) 30mg 12.7 (2.3-66.7) >50mg 5.6 (1.0-24.1) >75mg 5.9 (1.0-28.8)
Conclusion: Half the patients with incident RA were prescribed GCs in primary care. They received GCs for 25% of the time they were observed. Of those who received GCs, 80% received doses greater than 5mg per day and 40% more than 20mg/day. Patients spent 60% of their total duration on GCs taking doses greater than 5mg per day. The extent of GC prescribing for RA patients in primary care may be surprising to many rheumatologists and highlights the need to be aware of GC use in this setting in order to avoid excess exposure and associated side effects. Disclosure: R. J. Black, None; R. M. Joseph, None; M. Movahedi, None; M. Lunt, None; W. G. Dixon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/oral-glucocorticoid-prescribing-patterns-in-ukprimary-care-for-patients-with-rheumatoid-arthritis
Abstract Number: 1221
Characteristics and Outcomes of RA Patients Who Start Biosimilar Infliximab in South Korea Yoon-Kyoung Sung1, Soo-Kyung Cho1, Soyoung Won2, Chan-Bum Choi3, So-Young Bang4, Seung-Jae Hong5, Hyoun-Ah Kim6, Eunmi Koh7, Hye-Soon Lee8, Chang-Hee Suh9, Dae-Hyun Yoo10, Sang-Cheol Bae1 and BIOPSY investigators, 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 2Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 3Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 4Hanyang University Guri Hospital, Guri, South Korea, 5Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea, 6Ajou University Hospital, Suwon, South Korea, 7Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, 8Department of Rheumatology, Hanyang University Guri Hospital, Guri, South Korea, 9Department of Rheumatology, Ajou University Hospital, Suwon, South Korea, 10Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Recently biosimilar infliximab was approved in South Korea and it has been commonly used for rheumatoid
arthritis (RA) patients who are resistant to conventional DMARDs. The biosimilar infliximab have been shown to be equivalent to original infliximab in equivalent efficacy and safety in RA through several clinical trials, but its effectiveness and safety in daily practice has not yet been reported. This study aims to compare the characteristics of RA patients who use biosimilar infliximab with those of patients who start original infliximab and to identify the effectiveness and safety of biosimilar infliximab for RA patients in clinical practice. Methods: Using the prospective biologic DMARDs registry in Korea: BIOlogics Pharmacoepidemiologic StudY (BIOPSY), we selected RA patients who started either biosimilar or original infliximab. Baseline characteristics including sociodemographics, disease activity, previous or concurrent medications, and comorbidities of two groups were compared. Treatment outcomes such as DAS28-ESR and HAQDI scores observed in 6 or 9 months after starting infliximab were compared between two groups. Drug retention rates of both groups were also compared using Kaplan-Meier analysis and the reasons of discontinuation were described in each group. Results: A total of 98 RA patients who started either original or biosimilar infliximab were included in this analysis; 52 for biosimilar infliximab users (33.8 PY) and 46 of original infliximab users (50.2 PY). Baseline characteristics of two groups were quite similar in age, disease duration, and previous or current medications. Although baseline DAS28-ESR and HAQ-DI scores were not differed between two groups, swollen joints count was lower in biosimilar users than original users (6.1 ± 4.9 vs. 8.2 ± 5.4, P=0.05). Biologics-naïve patients were more common in biosimilar users but not significant statistically (92.3 % vs. 84.8 %, P=0.39). Early DAS28-ESR remission rate observed in 6 or 9 months after starting biosimilar and original infliximab were 18.6% and 15.6%, respectively (P =0.75). HAQ-DI changes were not different between two groups (0.4 ± 0.8 vs. 0.4 ± 0.7 P=0.85). The drug retention rates during 20 months were higher in biosimilar users, but there was no statistical significance (68.4% in biosimilar users vs. 53.1% in original users, p=0.16 by log-rank test). The most common reason of drug discontinuation was ineffectiveness in both groups (61.5% in biosimilar and 68.2% in original infliximab). Discontinuation due to infusion related reaction was only one case in each group. Conclusion: There was no significant difference in baseline characteristics of biosimilar infliximab users compared to original infliximab users in South Korea. Drug persistency of biosimilar infliximab for 20 months was comparable to that of original infliximab, and the reasons of drug discontinuation were similar between two groups. Disclosure: Y. K. Sung, None; S. K. Cho, None; S. Won, None; C. B. Choi, None; S. Y. Bang, None; S. J. Hong, None; H. A. Kim, None; E. Koh, None; H. S. Lee, None; C. H. Suh, None; D. H. Yoo, None; S. C. Bae, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/characteristics-and-outcomes-of-ra-patients-who-startbiosimilar-infliximab-in-south-korea
Abstract Number: 1222
The Risk of Tuberculosis (TB) in Rheumatoid Arthritis Patients Treated with TNF Inhibitors and the Safety of Resuming Biologic Dmards for Patients Who Developed TB after Anti-TNF Treatment Soo-Kyung Cho1, Dam Kim1, Hye-Jin Jeong2, Il Woong Sohn2, Soyoung Won3, Minkyung Han3, Jiyoung Lee3, Eun Jin Jang4, Sang-Cheol Bae1 and Yoon-Kyoung Sung1, 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 2Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 3Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 4Information Statistics, Andong National University, Andong-si, South Korea First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: The association between TNF inhibitor (TNFI) treatment and the development of tuberculosis (TB) has been confirmed through several observational studies. Current guidelines strongly recommend latent tuberculosis infection (LTBI) screening treatment before starting TNFI and they might reduce the risk of development of active TB in TNFI users. However, there is still limited evidence of the risk of TB in RA patients who used TNFI after introduction of LTBI screening and treatment guidelines. Moreover, the safety of resuming biologic DMARDs for RA patients who developed TB after anti-TNF treatment has not been well-known. This study aims to estimate the incidence of TB in RA patients who used TNFI after introduction of LTBI screening and treatment guidelines and to evaluate the safety of resuming biologic DMARDs for patients who developed TB after anti-TNFtreatment.
Methods: A retrospective cohort of RA patients who started TNFI was established using Korean national healthcare claims database between January 2009 and December 2013. There was 1 year wash-out period of biologic DMARDs to determine the incident users of biologic DMARDs. After excluding the patients who started biologics other than TNFI, we made an inception cohort for RA patients who started TNFI as a first biologic DMARD. Patients were followed for the development of TB or the last observational date (December 31, 2013). The development of the TB was defined as the appearance of ICD 10 code of TB plus at least 3 among 4 agents of isoniazid, rifampin, ethambutol, and pyrazinamide. Through this definition, the incidence rate (IR) per 100,000 person-year (PY) and standardized incidence ratio (SIR) of TB for TNFI starters based on total RA patients were calculated. We also classified the patients who developed TB into two groups; resuming biologic DMARD group vs. conventional DMARD group. After comparing the characteristics between two groups, the TB relapse rate among patients who resumed biologic DMARDs was estimated. Results: We included 4,638 RA patients who had started TNFI as the first biologic DMARD, contributing 8,542 PYs of follow-up. A total of 81 patients had been developed TB infection during follow-up. The IR and the SIR of TNFI users based on total RA patients were 1,100 per 100,000 PY [860-1,340/100,000 PY, 95% confidence interval (CI)] and 2.04 (1.62-2.54, 95% CI). If we restrict the maximal followup period in 1 year, the IR and SIR of TNFI starters increased to 1,660/100,000 PY and 3.08, respectively. Among the 81 patients who developed TB during follow-up, 30 patients (37.0%) had continued or resumed biologic DMARDs. Mean interval between TB development and resuming biologic DMARDs was 3.3 months. Two cases of TB were developed in 30 patients with observational period of 45.7 PY. Conclusion: The risk of TB in RA patients who start TNFI is still higher than that of total RA patients after introduction of LTBI treatment guidelines. Resuming biologic DMARDs after TB development should be undertaken with careful monitoring of TB relapse. Disclosure: S. K. Cho, None; D. Kim, None; H. J. Jeong, None; I. W. Sohn, None; S. Won, None; M. Han, None; J. Lee, None; E. J. Jang, None; S. C. Bae, None; Y. K. Sung, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-risk-of-tuberculosis-tb-in-rheumatoid-arthritispatients-treated-with-tnf-inhibitors-and-the-safety-of-resuming-biologic-dmards-for-patients-who-developed-tb-after-anti-tnf-treatment
Abstract Number: 1224
Infection Rate in HIV Patients Who Received TNF-a Inhibitor Therapy for Concomitant Autoimmune Diseases Sintawat Wangsiricharoen1, Colin Ligon2, Ahmad Dehrab3, Lydia Gedmintas4, Marisa Tungsiripat5, Clifton Bingham6, Carlos J. Lozada7 and Leonard H. Calabrese8, 1Chiang Mai University, Chiang Mai, Thailand, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Rheumatology, University of Miami Jackson Memorial Hospital, Miami, FL, 4Rheumatology, Brigham's Women's Hospital, Boston, MA, 5Infectious Disease, Cleveland Clinic Foundation, Cleveland, OH, 6Johns Hopkins University, Baltimore, MD, 7University of Miami Miller School of Medicine, Miami, FL, 8Rheumatic & Immunologic Dis, Cleveland Clinic Foundation, Cleveland, OH First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Few HIV-infected patients have been treated with tumor necrosis factor (TNF)-α inhibitor therapy for autoimmune diseases refractory to conventional therapies. Evidence supporting the safety of TNF-α inhibitor therapy in HIV-infected individuals is limited and based on isolated case reports and small series. Objective: To estimate the incidence of serious infections in patients with HIV infection who are treated with TNF-α inhibitors therapy for concomitant autoimmune diseases, and to compare these rates between certain CD4+ cell count and viral load levels. Methods: Using a unified search strategy of the electronic medical record EPIC, four centers identified HIV infected patients exposed to TNF-α
inhibitors. Patient characteristics and infection data were assessed via chart review in all HIV-infected patients who are ≥ 18 years old and have received TNF-α inhibitor therapy after HIV diagnosis between January 1999 and March 2015. Results: The inclusion criteria were met in 23 patients with 26 uses of TNF-a inhibitor therapy, 16 treated with Etanercept, 6 with Adalimumab and 4 with Infliximab. The median (range) age was 47 (20-66). The median (range) CD4+ cell count and viral load at therapy initiation was 541.5 (1-1100) and undetectable (undetectable to 298,281), respectively at time of biologic therapy initiation. These individuals provided 86.7 person-years of followup. Two (8.7%) experienced at least 1 serious infection episode (SIE) (pneumonia with empyema and MSSA chest tube infection), an overall incidence rate for all treatment courses of 2.3 per 100 patient-years (95% CI [Confidence Interval] 0.268.33). Both of them were on Etanercept before infectious episodes; at the time of the infection in both, viral load was < 50 and CD4+ cell count was increased from the time of TNF inhibitor initiation (209 and 804 cells/mm3 at time of SIE). There were no opportunistic infections. The incidence rate per 100 patient-years was 3.28 (95% CI 0.04-18.26) among patients with viral load > 500 copies/mL at therapy initiation and 2.08 (95% CI 0.03-11.6) among patients with viral load ≤ 500 copies/mL. One of them was on TNF inhibitor monotherapy while the other was on low-dose corticosteroid. Conclusion: This study suggests that TNF-α inhibitor therapy may have reasonable rates of SIEs in the range of those observed in registry data bases when used in patients with HIV infection under active care. Disclosure: S. Wangsiricharoen, None; C. Ligon, None; A. Dehrab, None; L. Gedmintas, None; M. Tungsiripat, None; C. Bingham, None; C. J. Lozada, AbbVie, 2,Pfizer Inc, 5; L. H. Calabrese, BMS, 8,Crescendo, 8,Abbvie, 5,Genentech and Biogen IDEC Inc., 8,Pfizer Inc, 5,Sanofi-Aventis Pharmaceutical, 5,Johnson & Johnson, 8. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/infection-rate-in-hiv-patients-who-received-tnf-ainhibitor-therapy-for-concomitant-autoimmune-diseases
Abstract Number: 1225
Long-Term Use of Biological Therapy and Discontinuation Rates in Rheumatoid Arthritis – Real World Patient Data Laurent Chanroux, Joan Casellas and Fara Mboge, Therapy Watch, Research Partnership, London, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Biologics (bDMARDs) have been shown to control disease progression in RA however there is still no cure for the disease and in many cases long-term use of these agents is required. Their cost and toxicity can be problematic over time and immunogenicity may cause their efficacy to diminish. The aim of our research is to better understand long-term bDMARD survival to guide disease strategies and maximise patient outcomes. Methods: We used data collected as part of an online treatment survey conducted among a panel of 288 US rheumatologists between July 2011 and December 2014. We analysed a total of 6,113 patient forms and focused our research on 4,557 bDMARD patients with complete treatment information and analysed their current DAS, joint count and perceived disease severity to assess their response to therapy over time. A discriminant analysis was also performed to understand the relationship between four different groups of patients (based on their time on a bDMARD) and a number of patient characteristics to understand their associated with sustained response to bDMARDs. Results: The 1st stage of our analysis showed that on average patients spent 29.5 months on their bDMARD (21.3 for switch patients). We observed
differences in the mean drug survival of bDMARDs: 36.1 months for etanercept, 28.2 for adalimumab, 42.2 for infliximab, 23.1 for rituximab, 21.7 for abatacept, 11.9 for tocilizumab, 16.6 for certolizumab pegol and 15.1 for golimumab. The reported drug survival rates at 1, 2, 3, 4 and 5 years were 60.8%, 40.2%, 27.5%, 19.7% and 14.0% respectively. These results matched the primary reasons given for switching bDMARD. Lack of long-term efficacy (> 6 months) was the most common reason (36.0%) followed by lack of initial response defined as ≤ 6 months (14.6%). Safety/tolerability issues were only chosen as a primary reason for switching in 10.9% of cases and immunogenicity was reported for 0.9% of patients. We saw little significant difference between patients based on their length of time on treatment. Patients on bDMARDs for ≤ 12 months were significantly more likely to be aged below 24 years (p 12 months were more likely to be aged > 60. The latter were also significantly more likely to be retired. However, patients treated for > 6 months were more likely to be considered to have mild RA by their Dr and while patients treated for > 12 months had higher mean DAS they typically had lower mean joint counts. The discriminate function showed a significant association between groups and the patient variables, accounting for 51.1% of between group variability. Closer analysis of the structure matrix showed only 2 significant associations, time since 1st ever bDMARD initiation (.832) and time since diagnosis (.712). The cross validated classification showed that 60.7% of cases were correctly classified. Conclusion: Our research emphasizes the fact that long-term response to bDMARDs varies considerably by patient and by drug. Lack of long-term efficacy is the most common reason for switching away from a bDMARD but immunogenicity is chosen in 1 PO discrepancies, hence total (%) RCTs > 95 (100%) Ref: Arthritis Rheumatol. 2014;66:2664-74 Disclosure: S. Lezcano, None; S. Sajib, None; A. Fan, None; M. Pathria, None; K. M. D. Torralba, None; N. A. Khan, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/discrepancies-between-registered-and-publishedprimary-outcomes-in-randomized-controlled-trials-of-rheumatoid-arthritis
Abstract Number: 1228
Estimating Under-Diagnosis of Rheumatoid Arthritis in Primary Care Data from the UK Clinical Practice Research Datalink Julian Gardiner1, Bowen Su1, Benjamin Ellis2 and Michael Soljak1, 1Department of Primary Care and Public Health, Imperial College London, London, United Kingdom, 2Arthritis Research UK, London, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: The prevalence of rheumatoid arthritis (RA) in primary care electronic health records (EHRs) is much lower than patient self-reports from population surveys, which may be due to under-diagnosis. The objectives of this study were to identify possible RA cases using a diagnostic algorithm developed from the 2010 EULAR/ACR criteria, and to compare them with EHR RA diagnosis cases, in order to estimate potential under-diagnosis rates. Methods: Patients’ EHRs in the UK Clinical Practice Research Datalink (CPRD) contain diagnostic, clinical and test information. We extracted relevant data to identify patients with diagnosed RA and possible additional RA cases using an algorithm consisting of four parts, including joint involvement and symptom duration, acute phase reactants, and serology tests. Clinical findings, diagnostic labels and results of tests
ordered by consultant rheumatologists are not available in CPRD. In the EULAR/ACR classification criteria patients can score up to five points for any joint involvement, up to three points for positive serology, one point for positive acute phase reactants and one point if the duration of symptoms is greater than six weeks. In line with the classification criteria we defined those with a score of six or more as “algorithm-diagnosed RA cases”. The incidence of RA was calculated from the number of CPRD patients receiving a new RA diagnosis in that year divided by the denominator. The prevalence was calculated from the cumulative number of patients receiving an RA diagnosis up to and including a given year (as far back as CPRD records allow, with patients who have died being removed). Results: A total of 88,299 patients had a primary care EHR diagnosis of RA, and an additional 12,928 were defined as algorithm-diagnosed RA cases. The prevalence of RA was 0.49% for EHR-diagnosed RA, rising to 0.58% if algorithm diagnosed cases are included (Table 1.). This has risen steadily over time, possibly because of more complete diagnostic coding. The incidence of EHR-diagnosed RA is approximately 30.4/100,000 over the period 2005-14 compared with 6.0/100,000 algorithm-diagnosed cases, an overall incidence rate of 36.4/100,000. There were 3,091 patients diagnosed by both a doctor and the algorithm. The mean age of EHR-diagnosis patients was 60.2 years compared with 57.7 years for the algorithm-diagnosis group, which may suggest diagnostic delay. Table 1. Incidence and prevalence of RA in the CPRD. Figures are per 100,000 people. Year Incidence Incidence of Total Prevalence Prevalence Total Denominator of doctor algorithm incidence of of doctor of algorithm prevalence diagnosed diagnosed RA diagnosed diagnosed of RA RA RA RA RA 2000 21.16 4.55 25.71 220.46 18.65 239.12 11,915,756 2001 24.19 5.29 29.48 236.13 23.89 260.02 11,982,172 2002 24.99 5.94 30.93 252.24 29.63 281.86 12,042,662 2003 27.10 7.13 34.22 269.58 36.47 306.05 12,096,190 2004 31.78 6.96 38.74 290.88 42.94 333.82 12,151,149 2005 30.49 6.92 37.41 310.31 49.56 359.87 12,204,412 2006 29.50 6.67 36.17 329.37 55.67 385.03 12,258,669 2007 28.40 6.43 34.84 346.74 61.35 408.09 12,311,226 2008 27.83 7.12 34.95 363.32 67.65 430.97 12,363,171 2009 28.15 6.37 34.52 380.32 73.05 453.37 12,411,546 2010 25.79 6.14 31.93 394.83 78.38 473.21 12,457,701 2011 25.96 5.65 31.60 409.49 83.02 492.51 12,499,758 2012 27.90 5.50 33.40 427.27 87.48 514.75 12,535,602 2013 38.84 4.87 43.71 455.23 91.19 546.42 12,563,940 2014 41.01 4.10 45.11 487.74 94.21 581.94 12,585,816 Conclusion: The algorithm developed from the 2010 ACR/EULAR criteria identified a significant number of possible RA cases, or patients who may be at high risk of developing RA, in addition to those with a coded diagnosis. Insufficiently accurate coding of joint involvement by general practitioners prevented more precise scoring and classification. Delayed or under-diagnosis has implications for prognosis in these patients. Disclosure: J. Gardiner, None; B. Su, None; B. Ellis, None; M. Soljak, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/estimating-under-diagnosis-of-rheumatoid-arthritis-inprimary-care-data-from-the-uk-clinical-practice-research-datalink
Abstract Number: 1229
Regional Variation in Measured Detection of Ankylosing Spondylitis Jason Shafrin1, Jin Joo Shim1, Caroline Huber1, Jenny Griffith2, Arijit Ganguli2 and Wade Aubry3, 1Precision Health Economics, Los Angeles, CA, 2AbbVie Inc., North Chicago, IL, 3University of California, San Francisco, San Francisco, CA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015
Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Patients suffering from ankylosing spondylitis (AS) often receive a delayed or mis-diagnosis, as this condition is frequently confused with mechanical back pain from other causes. If AS is not properly identified, patients can receive inadequate care, delaying disease-specific treatment, which may contribute to decreased physical functioning, quality of life, excessive use of narcotic analgesics, and disease progression. This study looks at regional variation in AS detection and examines whether regions that are better able to detect AS also are less likely to provide inappropriate care. Methods: A large commercial claims database covering the years 2008 through 2013 was used to measure geographic variation in AS and back pain detection and potentially inappropriate health resource utilization. All adults with 12 months of continuous eligibility in the dataset were included. Measured detection was defined as the prevalence of AS (ICD-9 codes: 720.0) and measured detection for back pain was defined as (720.1-720-.9, 721.x, 722.x, 723.0-723.8, 724.x, 739.1x-739.4x, 846.x, 847.x). We measured the share of patients with back pain who used narcotic analgesics and corticosteroid injections as a proxy for unnecessary healthcare utilization, as well as medical and pharmacy costs within each metropolitan statistical area (MSA) using generalized linear models adjusting for age, gender, and comorbidities. Geographic variation across MSAs was evaluated using standard deviation (SD), interquartile range (IQR) and coefficient of variation (CV). Results: In the data, 21,215,151 patients were diagnosed with back pain or AS. Nationally, 37 per 100,000 (0.037%, SD: 0.023%, IQR: 0.024%0.043%) individuals were diagnosed with AS. A majority of MSAs (74.9%, 293 of 391 MSAs) had AS measured detection below the average in the data, and all MSAs (391 of 391) had AS measured detection below the 0.55% US AS prevalence estimate from the 20092010 National Health and Nutrition Examination Survey (NHANES). The CV for AS measured detection (0.631) was almost 2.5 times higher than the CV for measured detection of back pain alone (0.256). Based on our regression model, moving from an MSA at the 10th percentile of AS measured detection to one at the 90thpercentile would decrease the share of patients using narcotic analgesics (-1.0%) and steroids (-7.9%), but would increase spending on disease-modifying antirheumatic drugs (+14.4%). The net effect would be a decrease in both total pharmacy costs (-7.1%) and total costs (-2.1%). Conclusion: Detection of AS varies dramatically across MSAs in the US and is significantly below prevalence estimates from large national surveys. Further, areas with higher rates of AS measured detection were less likely to use narcotic analgesics and steroids, suggesting that patients with back pain from AS who are not accurately diagnosed with AS may be receiving inadequate care. Increased patient and provider awareness regarding the treatment of inflammatory conditions—such as AS—that cause back pain is needed to ensure appropriate and timely care. Disclosure: J. Shafrin, Precision Health Economics, 5; J. J. Shim, Precision Health Economics, 5; C. Huber, Precision Health Economics, 5; J. Griffith, AbbVie, 3,AbbVie, 1; A. Ganguli, AbbVie, Inc., 3; W. Aubry, Precision Health Economics, 5. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/regional-variation-in-measured-detection-ofankylosing-spondylitis
Abstract Number: 1230
Only One-Third of Patients with Spondyloarthritis Are Managed By Rheumatologists Linda E. Dean, Gary J. Macfarlane and Gareth T Jones, Musculoskeletal Research Collaboration (Epidemiology Group), University of Aberdeen, Aberdeen, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM
Session Time: 9:00AM-11:00AM Background/Purpose: The prevalence of Ankylosing Spondylitis (AS) in Europe has been estimated in a number of studies, some based on clinic populations, others from general population surveys, and prevalence has been shown to range between 9 and 49/10,000. However, to date, none have attempted to determine the prevalence in primary and secondary care within the same population. Knowing, not only the prevalence, but also the proportion of patients managed in specialist services has important implications in terms of health service planning and resource allocation. Thus, the aim of the current study was (a) to determine, in a single population, the prevalence of AS plus the proportion of patients actively managed in secondary care; and (b) to examine differences in basic characteristics of these patients. Methods: Data from the Primary Care Clinical Informatics Unit (PCCIU) and the Scotland Registry for Ankylosing Spondylitis (SIRAS) were utilised to estimate the prevalence of AS in Scotland, in primary and secondary care respectively. Established in April 2000, and covering around a third of the entire population, the PCCIU collected data from a representative sample of general practices across Scotland, UK, via Read Codes: a coded thesaurus of clinical terms used to document all diseases (including AS). SIRAS is a registry collecting clinical and patient-reported outcomes on all patients with a clinical diagnosis of AS being seen within secondary care clinics in Scotland. Patients were identified via clinic lists, if available, or through a review of recent physician correspondence for evidence of an AS diagnosis. Data for the denominator was taken either from the PCCIU database (total patients) or the mid-year population estimate for Scotland, published by the National Records of Scotland. Results: In April 2007, the PCCIU comprised 1,469,688 persons, of whom 1,964 had received a diagnostic code for AS (prevalence: 13.4 per 10,000; 95%CI 12.8-14.0 per 10,000). The SIRAS registry identified 1,686 patients in secondary care; from a population of 3,578,984 (prevalence: 4.7 per 10,000; 4.5-4.9 per 10,000). There was no difference in sex between the two populations, although patients managed in secondary care were more likely to be younger (mean age 51 vs 62yrs; p 700,000 surgeries performed annually in the United States. Racial variation in TKR utilization has been documented in population-based studies, however, there is a paucity of prospective data on disparities in TKR use in patients with osteoarthritis (OA). We aimed to evaluate racial disparity in incident TKRs in a cohort of patients with physiciandiagnosed OA followed in a current clinical trial. Methods: Vitamin D and Omega-3 Trial (VITAL) is an ongoing nationwide, racially diverse, community-based, randomized controlled trial of 25,874 males age ≥50 and females age ≥55. We identified a knee pain subgroup with probable knee OA based on: a) self-reported knee pain symptoms in walking 2-3 blocks; b) pain > 1 day/week for > 1 year; and c) a doctor's diagnosis of OA. This subgroup completed a modified Western Ontario and McMaster’s Universities Osteoarthritis Index (WOMAC) questionnaire, and reported prior TKR and laterality (103 people with bilateral TKR at baseline were excluded.) Participants reported new TKR, laterality and date, over the 2 year follow-up. We compared baseline WOMAC scores by race using t-tests. In multivariable-adjusted logistic regression analyses, we investigated the association of race with TKR risk, adjusting for potential confounders including age, sex, race, geographic location, WOMAC pain, function and stiffness, body mass index, income, education level, and self-reported depression. Results: At baseline, 1508 (5.8%) of trial participants were eligible for the knee pain cohort. Of those, 1241 (94.7% of mailed) returned a baseline knee pain questionnaire and 1019 (82%) returned a follow-up questionnaire, a mean of 27 (±4) months after baseline. Within this group, 133 (13%) reported TKR in follow-up. Among those who underwent TKR, mean age was 68 (±7) years, 65% were female, and 13% were Black. Among those who did not have TKR, mean age was 67 (±7) years, 66% were female and 24% Black. All baseline WOMAC score means were significantly higher among Black than White patients. (Table)In multivariable logistic regression analyses, only race and WOMAC pain score were related to TKR incidence. The odds ratio of TKR among Black compared to White patients was 0.40 (95% CI 0.22, 0.74). After adjustment for baseline WOMAC pain and stiffness scores, the odds of TKR among Black patients was further reduced to 0.32 (0.18, 0.58). Conclusion: Despite having worse self-reported worse knee pain, function and stiffness at baseline, and having demonstrated a high level of engagement by virtue of volunteering for a large randomized trial, Black patients had much reduced odds of undergoing TKR compared to White patients. This community-based, racially diverse cohort is unique as subjects have physician-diagnosed OA, and have been followed prospectively. Our data highlights the need for further efforts to correct this large racial disparity. Table. Baseline WOMAC Scores in Black vs. White Patients Disclosure: L. MacFarlane, None; N. Cook, None; I. M. Blacks Whites p** Lee, None; J. N. Katz, None; K. H. Costenbader, Arthritis WOMAC Pain Care and Research, 5,International Journal of Clinical 44.81(20.94) 32.21 (15.79) p130) and statin use. Our cardiology team devised a specific protocol to best risk assess these patients per EULAR guidelines. Results: Since the launch of our program, 722 RA patients have been seen by the rheumatology practice, 99 (14%) of these patients agreed and were then referred to the RA-CVD clinic. Screening for diabetes and hypercholesterolemia has improved by 60% with the implementation of the program. To date, 13 patients have undergone full risk assessment, however not all patients have been seen partially due to cardiology appointment lag time. Of these patients, 5/13 (38%) patients were started on a statin based on their ASCVD score. Conclusion: Our study suggests that the creation of a RA-CVD workflow significantly increased the rates of risk factor screening and appeared to provide a forum for necessary interventions. However, lack of cardiology access may limit the strength this program. Disclosure: B. Goldstein, None; J. Zell, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/advocating-for-rheumatoid-arthritis-andcardiovascular-health-arch-a-collaborative-and-systems-based-approach-to-improve-access-to-care
Abstract Number: 1299
Can Bone Marrow Lesions be Scored More Reliably and Responsively in Knee Osteoarthritis Using a Web-Based Overlay System (KIMRISS) Than By Standard MRI Osteoarthritis Knee Scoring (MOAKS)? Data from the Osteoarthritis Initiative and a Prospective Trial of Adaluminab Therapy Jacob Jaremko1, Mark Buller2, Dean Jeffery2, David McDougall3, Benjamin Smith2, Robert G Lambert1 and Walter Maksymowych4, 1Radiology, Radiology, University of Alberta, Edmonton, AB, Canada, 2Radiology & Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada, 3Radiology, University of Alberta, Edmonton, AB, Canada, 4Medicine, University of Alberta, Edmonton, AB, Canada First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Imaging of Rheumatic Diseases Poster II: X-ray, MRI, PET and CT Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Bone marrow lesions (BML) relate to pain and prognosis in knee osteoarthritis. The Knee Inflammation MRI Scoring System (KIMRISS) offers simple template-assisted binary BML scoring via a web-based interface. We tested whether KIMRISS was more reliable and responsive to change than the commonly used MRI Osteoarthritis Knee Score (MOAKS) system, particularly for naïve readers. Methods: The KIMRISS web-based overlay system separates the knee into multiple small regions, each scored 0 (no BML) or 1 (BML present). The reader scrolls through sagittal fluid-sensitive MRI slices and mouse-clicks (or contacts a touch-screen) each region in which BML is present. Scores are tabulated and exported automatically. In contrast, MOAKS BML grading is performed in 9 larger knee regions based
on the number of lesions present and percentages of the region containing edema and cystic change. Exercise 1 assessed reliability, in observational data from the Osteoarthritis Initiative. We had 40 subjects at baseline and 1 year followup (80 MRI). Expert readings were performed by two radiologists (6 and 11 years experience) familiar with KIMRISS, and consensus score computed as the average of these readings. Two radiology residents naïve to KIMRISS and MOAKS reviewed a 55-slide presentation describing KIMRISS, three scored reference cases, and a published manuscript describing MOAKS. These readers then scored the same data by KIMRISS and MOAKS. All readers were blinded to scan time point (baseline vs. follow-up). Exercise 2 assessed responsiveness, using data from an open-label pilot study testing adalimumab (Humira) knee OA therapy. Two blinded experienced readers scored BML by MOAKS and KIMRISS at enrolment and 12 weeks post-therapy in all 16 patients (32 MRI). Reliability statistics were calculated using intra-class correlation coefficients (ICC), with differences significant at p100mm3. Results: Patients were 78% female, 77% Caucasian, mean (standard deviation) age 55.9 (13.3) years, symptom duration 4.2 (5.1) years, DAS28 4.48 (1.40), HAQ-DI 0.81 (0.71), with 50% using DMARD or biologic over the preceding 3 months. Mean erosive damage was low at 32.3 (78.5) mm3. Model 1 (R2=0.296, p0). Results: In total, 486 patients (mean age 33.0 (SD 8.6) years, 50% males) had at least one radiograph available. At baseline, scores ranged from 0 and 21.6 for the mSASSS (30% of the maximum of the scale), 20.6 for RASSS (25% of maximum), 6 for SASSS (8% of maximum), 8.5 for BASRI-spine (71% of maximum) and 10.25 for BASRI-spine with thoracic spine (64% of maximum). Status scores and 2-year progression scores available are shown in the table. The proportion of patients with any 2-year change was the following: 9.9% for mSASSS, 10.7% for RASSS, 6.9% for SASSS, 19.2% for BASRI-spine and 22.0% for BASRI-spine with thoracic spine. Absolute change scores (table) showed that the mSASSS and RASSS captured most change. 2-year RASSS progression occurred in a balanced way across segments (cervical, thoracic and lumbar), when taking the number of VCs included per segment. All scores had acceptable reliability. In what concerns feasibility, all scores seemed to be feasible, but the BASRI-spine (+/- thoracic spine) was more frequently missing (up to 15% of the cases), as it requires also the availability of SI joints. Table - Status and 2-year progression for the different radiographic scoring methods
mSASSS RASSS SASSS BASRI BASRI spine spine mean mean mean with (SD) (SD) (SD) mean (SD) thoracic n = 481 n = 481 n = 483 n = 447
mean (SD) n = 442
STATUS SCORES 0.57 0.54 0.17 (2.37) (2.34) (1.03) Cervical 0.36 0.34 -segment (1.69) (1.66) Lumbar segment 0.21 0.16 0.17 (1.09) (1.04) (1.03) Lumbar segment -0.19 -with thoracic (1.13) segment included Thoracic -0.03 -segment (0.28) Lumbar anterior --0.16 (1.03) Lumbar --0.00 posterior (0.02) SI joints ---Total score
1.35 (1.62) 0.16 (0.55) 0.18 (0.54) --
1.46 (1.80) 0.17 (0.55) 0.19 (0.55) --
0.09 (0.38) --
1.00 1.00 (1.13) (1.13) 2-YEAR PROGRESSION SCORES mSASSS RASSS SASSS BASRI BASRI spine spine n = 322 n = 319 n = 335 with n = 287 thoracic
0.27 (1.57) Cervical 0.19 segment (1.16) Lumbar segment 0.08 (0.63) Lumbar segment -with thoracic segment included Thoracic -segment Lumbar anterior -Lumbar posterior SI joints
0.36 0.15 (1.74) (0.78) 0.17 -(1.18) 0.13 0.15 (0.66) (0.78) 0.18 -(0.84) 0.06 (0.38) --
0.05 (0.72) 0.04 (0.36) 0.01 (0.40) --
n = 268 0.07 (0.83) 0.03 (0.35) 0.02 (0.35) --
0.13 (0.65) 0.02 (0.33) --
0.00 (0.32) --
Conclusion: The existing scoring methods to assess radiographic damage performed well in early phases of axSpA. The mSASSS and RASSS captured most change, but there was no gain in additionally scoring the thoracic spine for the RASSS. The mSASSS remains the most sensitive and most adequate scoring method in axSpA, including early phases of the disease. Disclosure: S. Ramiro, None; P. Claudepierre, None; R. van den Berg, None; V. Navarro-Compán, None; A. Feydy, None; M. A. d'Agostino, None; D. Loeuille, None; M. Dougados, None; M. Reijnierse, None; D. van der Heijde, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/which-score-to-use-for-radiographic-damageassessment-of-the-spine-in-early-axial-spondyloarthritis-two-year-data-from-the-desir-cohort
Abstract Number: 1327
Five-Year Follow-up of Radiographic Sacroiliitis: Progression As Well As Improvement? Alexandre Sepriano1,2, Martin Rudwaleit3, Joachim Sieper4,5, Rosaline van den Berg6, Robert B. M. Landewé7 and Désirée van der Heijde8, 1Rheumatology, Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands, Leiden, Netherlands, 2Rheumatology, Hospital de Egas Moniz - CHLO, Lisbon, Portugal, Lisbon, Portugal, 3Rheumatology, Dept of Medicine, Charité - Campus Benjamin Franklin, Berlin, Germany, Berlin, Germany, 4German Rheumatism Research Centre, Berlin, Germany, Berlin, Germany, 5Rheumatology, Charité - Campus Benjamin Franklin, Berlin, Germany, Berlin, Germany, 6Leiden University Medical Center, Leiden, Netherlands, 7Department of Rheumatology, Amsterdam Rheumatology Center, Amsterdam, the Netherlands, Amsterdam, Netherlands, 8University Hospital, Maastricht, Netherlands First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Imaging of Rheumatic Diseases Poster II: X-ray, MRI, PET and CT Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Detecting sacroiliitis on plain pelvic X-rays is known to be difficult, resulting in large variability regarding presence/absence of radiographic sacroiliitis. In addition, the number of patients with radiographic sacroiliitis in a cohort of patients with axial SpA can be expected to (slightly) increase or remain stable over time but certainly not decrease. We have investigated the change of pelvic X-ray abnormalities over time in the Assessment of SpondyloArthritis international Society (ASAS) validation cohort. Methods: In the ASAS study, 975 patients with either chronic back pain (>3 months) of unknown origin beginning 12) questionnaires respectively. The mean levels of VAS-pain, HAQ and RAQoL scores were significantly higher in patients having neuropathic pain than in patients not having (p10 years, and 13.4 % were fellows. The majority of these providers cared for 1-4 patients (70.5%) and diagnosed 0-3 new cases (90.2%) each year. Most providers felt “very or moderately” confident with diagnosing (81.8%) and treating (86.6%) patients with CNO. Reported bone biopsy frequencies were: never 0%, rarely 11.6%, sometimes 25.6%, often 39.7%, or always 23.1%. The top three reasons for performing a biopsy were constitutional findings (84.8%), unifocal bone lesions (82.6%), and nocturnal bone pain (57.6%). The top three reasons for not performing a biopsy were involvement of typical sites such as the metaphyses of long bones and clavicles (83.5%), presence of multiple bone lesions (79.1%), and presence of conditions known to be associated with CNO, such as psoriasis and inflammatory bowel disease (63.7%). Biopsy sites were usually determined by the orthopedic surgeon or interventional radiologists (67.5%). Among all imaging modalities, regional MRI and X rays were most commonly used. 36.5% of responders used whole body MRI often or always. 53.3% of responders used imaging regularly to monitor disease activity, 53.1% of which monitored every 6 months and 25% of which obtained imaging every 12 months. Almost all responders (98.3) routinely prescribed NSAIDs as initial therapy. For patients who failed NSAID treatment, methotrexate (68.6%), TNF inhibitors (66.9%) and bisphosphonates (46.6%) were the next most commonly used treatments. Presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion: The diagnostic approach and disease activity monitoring for CNO varied among physicians. NSAIDs remained the first line treatment for CNO. Methotrexate, TNF inhibitors and bisphosphonates were most commonly used after NSAIDs failed. These findings provide important background to move forward with development of consensus treatment plans for CNO. Funded by NIAMS, Friends of CARRA and the Arthritis Foundation. Disclosure: Y. Zhao, None; F. Dedeoglu, None; P. J. Ferguson, None; S. Lapidus, None; R. Laxer, None; S. C. Li, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/physicians-perspectives-on-the-diagnosis-andtreatment-of-chronic-nonbacterial-osteomyelitis
Abstract Number: 1446
Long-Term Effectiveness and Safety of Abatacept in Juvenile Idiopathic Arthritis: Interim Results from the Abatacept in JIA Registry Daniel J Lovell1, N Ruperto2, S Spalding3, JA Dare4, R Cimaz5, V Stanevica6, RK Vehe7, N Tzaribachev8, G Horneff9, M Trachana10, TA Simon11, HI Brunner12 and A Martini2, 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Istituto G. Gaslini Pediatria II Reumatologia, Genova, Italy, 3Cleveland Clinic, Cleveland, OH, 4University of Arkansas Medical Center, Little Rock, AR, 5Azienda Ospedaliero-Universitaria Meyer, Florence, Italy, 6Riga Stradins University, Riga, Latvia, 7University of Minnesota, Minneapolis, MN, 8Pediatric Rheumatology, Bad Bramstedt, Germany, 9Asklepios Klinik Zentrum für Allgemeine Paediatrie und Neonatologie, Sankt Augustin, Germany, 10Hippokration General Hospital, Thessaloniki, Greece, 11Bristol-Myers Squibb, Hopewell, NJ, 12Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects Posters. Juvenile Arthritis and Miscellaneous Rheumatic Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Abatacept (ABA) is a widely approved and used biologic in children with juvenile idiopathic arthritis (JIA). The purpose of this study was to describe the longitudinal effectiveness and safety of ABA in JIA patients (pts). Methods: Using a standardized protocol, clinical sites in the Pediatric Rheumatology Collaborative Study Group (PRCSG) and Paediatric Rheumatology International Trial Organization (PRINTO) enrolled JIA pts currently on or starting ABA in this longitudinal registry. Planned duration of follow-up is 10 yrs. Visits are every 3 mths for Yr 1, every 6 mths for Yrs 2–5 and annually for Yrs 6–10. After ≥4 mths on ABA, pts remain in the registry even if ABA is stopped. Data shown are those collected through March 26, 2015 (up to 2 yrs follow-up). Results: Overview. Of 146 JIA pts enrolled, 133 provided data for this analysis (6 had no data entry; 7 discontinued the study: 1 lost to follow-up, 1 withdrew consent, 3 moved to other site, 2 other). The total person-yrs of observation were 79.4: 67.9 yrs on ABA, 11.5 after ABA. In this registry, 33% (44/133) of pts were new starts on ABA and 28% (38/133) were biologic naïve; 39% had received ABA treatment for 0–1 yrs and 28% for 1–2 yrs. ABA was continued during follow-up in 85% of pts (113/133). Reasons for ABA discontinuation were inefficacy (18), surgery (1) and therapy complete (1). Baseline. 86% of pts were female, mean/median: age at enrollment was 13.4/13.8 yrs, disease duration was 5.9/5.4 yrs, height percentile (WHO standards for healthy children) 47.9/52.8, weight percentile 50.8/48.2 and 3.0/1.0 active joints. Baseline clinical, functional and HRQoL scores are shown in the Table. 15% had a history of uveitis and 4% had active uveitis. JIA subtype was systemic 3%, oligoarticular 21%, polyarticular RF– 54%, polyarticular RF+ 10%, psoriatic 5%, enthesitis-related 2%, undifferentiated 6%. 86% were taking a concomitant JIA medication (64% MTX, 49% NSAIDs, 17% systemic steroids, 5% leflunomide, 5% hydroxychloroquine, 1% cyclosporine, 1% sulfasalazine). ABA was given IV every 4 weeks in 83% and SC weekly in 17%. Followup effectiveness. Results up to 2 yrs are shown in the Table. Follow-up safety. Eleven AEs were seen (10 serious; all single occurrences) in 10 pts (8% of study population) for an AE rate of 12.6 per 100 pt-yrs of exposure (95% CI 6.9, 21.0). There were 2 infections of special interest (1 non-serious, candida esophagitis; 1 serious, methicillin-resistant Staphylococcus aureus wound infection). 1/133 ( 3,000 ng/dL, and 250 mg/dL, respectively. Other organ dysfunctions were defined as below: ·
Coagulopathy: fibrinogen level 5.8 mg/dL.
Hematological dysfunction: counts below normal limits, or 50% reduction in hemoglobin or leukocytes.
Univariate and multivariate statistical analyses were performed to identify correlates of MAS, and entered into a logistic regression model to assess independent predictors of MAS. Results: A total of 1,111 patients were included. Despite the statistically significant association in Univariate analysis, logistic regression did not identify a meaningful association with kidney, lung, or cardiovascular system (CVS) dysfunction (Table-1). Six independent parameters strongly correlates with MAS includes: central nervous system dysfunction (CNS), HBD dysfunction, coagulopathy, hematologic dysfunction, elevated ferritin and TG. Presence of 2 out of these 6 parameters was considered suggestive of MAS and 3 out of these 6 parameters was found to be confirmatory. Conclusion: MAS is associated with dysfunctional reticuloendothelial clearance, manifesting as CNS, hematologic, hepatobiliary, and coagulation dysfunction, with high levels of ferritin and TG. Presence of MAS should be suspected when at least 2 of the 6 parameters are noted, which should prompt further investigation and early identification.
Disclosure: K. S. Goh, None; F. Minoia, None; A. Ravelli, None; R. Q. Cron, None; B. Shakoory, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-organ-based-diagnostic-approach-to-macrophageactivating-syndrome-in-children-demonstrates-impaired-reticuloendothelial-system-clearance
Abstract Number: 1458
Association of Chronic, Extreme Elevation of Serum IL-18 with the Development of Macrophage Activation Syndrome in a Cohort of Autoinflammatory Disease Patients: A Potential Diagnostic Biomarker? Scott Canna1, Adriana Almeida de Jesus2, Yan Huang3, Sushanth Gouni1, Guangpu Shi4, Igal Gery4 and Raphaela Goldbach-Mansky3, 1Molecular Immunology and Inflammation Branch, NIAMS/NIH, Bethesda, MD, 2Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 3Translational Autoinflammatory Diseases Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 4National Eye Institute/NIH, Bethesda, MD First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects Posters. Juvenile Arthritis and Miscellaneous Rheumatic Diseases Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Macrophage Activation Syndrome (MAS) is a life-threatening systemic inflammatory syndrome that complicates several rheumatic diseases. Current MAS-related serum biomarkers (ferritin, neopterin, CD163, and CD25) mark active disease but normalize with quiescence and may lack specificity. Serum IL-18 elevation has been associated with many inflammatory and infectious diseases, but extremely high levels have been reported in Still’s Disease and Systemic Juvenile Idiopathic Arthritis, particularly in patients with a history of MAS. Methods: We measured serum levels of several cytokines across a complex cohort of patients with idiopathic or genetically-defined autoinflammatory diseases (NCT00059748). Samples were obtained from healthy adults (24 patients) and children (4), and patients with cryopyrinopathies (Neonatal Onset Multisystem Inflammatory Disease/NOMID (18) and Muckle-Wells Syndrome (1)), NLRC4-MAS (2), Non-infectious Osteomyelitis (3), Deficiency of IL-1 Receptor Antagonist (3), CANDLE (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (3), SAVI (STING-Associated Vasculopathy with onset in Infancy (2), XIAP-deficiency (2) and undifferentiated (11). Cytokines were measured by Bio-Plex Luminex technology, except IL-37 (adipogene) and IL-18BP (R&D systems). Results: We examined 142 samples from 27 controls and 49 patients. Of these patients, 13 had a clinical history of one to 4 episodes of MAS (as determined by the investigators based on the criteria established by Ravelli et al., J. Pediatr. 2005). Serum levels for total active IL-18, IL-18 binding protein (BP), and IL37 in healthy controls were 29-308, 3648-7889, and 40-505 pg/mL, respectively. Median serum IL-18 was 8773 (Interquartile Range (IQR) 1560-13581) pg/mL in patients with a history of MAS, and 176 (IQR 88-432) pg/mL in those without (p=30kg/m2). Average time after surgery was 30.8±16.1 months. Mean post-operative WOMAC pain score was 13±3.2, WOMAC stiffness score was 7±1.4, WOMAC function score was 48±18.4. Mean TSK was 43.0±8.7 and mean FJS-12 score was 66.1±21.5. Correlations between FJS-12 and WOMAC and TKS scores were as follows: r=-0.68 for WOMAC-Pain, r=-0.53 for WOMAC-Stiffness, r=-0.65 for WOMAC-Function, and r=-0.63 for TKS in patients with TKA. Correlations between FJS-12 and WOMAC function score and TKS scores were as follows: r=-0.58 and r=-0.62 in patients with THA. Conclusion: Assessing patients’ perception about their artificial joint is becoming more important in clinical area following total joint arthroplasty. The true success of the surgery may not equate to the sum of a set outcome variables. Long-term follow-up with PROs showed that there is a need for a greater focus on understanding the perspectives of patients following arthroplasty surgery to improve the efficacy of interventions focused on better functional outcomes in TKA and THA recipients. References:
1)Bolink SA, Grimm B, Heyligers IC. Patient-reported outcome measures versus inertial performance-based outcome measures: A prospective study in patients undergoing primary total knee arthroplasty. Knee. 2015 May 29. 2)Behrend H, Giesinger K, Giesinger JM, Kuster MS. The "forgotten joint" as the ultimate goal in joint arthroplasty: validation of a new patient-reported outcome measure.J Arthroplasty. 2012 Mar;27(3):430-436. Disclosure: G. I. KINIKLI, None; H. GUNEY, None; S. ONAL, None; C. SARIAL, None; D. DONDER, None; I. YUKSEL, None; O. CAGLAR, None; G. KINIKLI, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/can-patients-forget-their-artificial-joint-afterarthroplasty
Abstract Number: 1491
Effects of Drug Induced Toxicity on Patient Reported Outcomes in Early Rheumatoid Arthritis Treated-to-Target Using Conventional Triple DMARD Therapy Nasir Wabe 1, Michael Sorich2, Mihir Wechalekar2,3, Leslie Cleland3, Leah McWilliams3, Anita Lee4,5, Llew Spargo4, Robert Metcalf3, Cindy Hall4, Susanna Proudman4,5 and Michael D. Wiese6, 1School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia, 2Flinders University, Adelaide, Australia, 3Royal Adelaide Hospital, Adelaide, Australia, 4Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, 5Discipline of Medicine, University of Adelaide, Adelaide, Australia, 6University of South Australia, Adelaide, Australia First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Quality Measures and Quality of Care Poster Session (ARHP): Clinical Practice/Patient Care Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: While the introduction of the treat-to-target (T2T) strategy is associated with lower disease activity scores in rheumatoid arthritis (RA), the potential for increased toxicity due to more intensive use of concurrent DMARDs could adversely affect patient reported outcomes (PROs). The objective was to determine the effects of DMARD related toxicity on PROs in early RA patients treated according to T2T strategy for 3 years Methods: A total of 149 patients from an inception cohort of recent onset RA were included. The occurrence and severity of toxicity were monitored at each clinic visit over three years. PROs studied were function (measured using health assessment questionnaire), helplessness (assessed using the rheumatology attitudes index), pain, fatigue and patient global assessment (PGA) all assessed using a 100mm visual analogue scale and health-related quality of life (HRQoL) (assessed using SF-36). For each PRO, the effect of drug withdrawal was measured by comparing mean change from baseline among patients with no/temporary withdrawal versus those with permanent drug cessation. The effects of the frequency of minor side effects, frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression. Results: After 3 years, 56 (37.6%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n=93) achieved significantly greater improvement in function, pain, fatigue and PGA compared to their counterparts (n=56). Drug-related toxicity did not have a significant effect on HRQoL and helplessness (Table 1).
Table 1: Improvement in PROs, mean change (SE), according to withdrawal due to toxicity No/temporary Permanent Between group P-value withdrawal withdrawal mean differences (n=93) (n=56) (95%CI) Function -0.54 (0.06) -0.31 (0.09) -0.23 (-0.44 to - 0.033 0.02) Pain -39.82 (3.44) -25.02 (5.50) -14.80 (-27.03 to - 0.018 2.56) Fatigue -29.14 (3.43) -14.76 (4.89) -14.38 (-25.97 to - 0.015 2.80) PGA -29.64 (3.16) -17.00 (4.21) -12.64 (-23.03 to - 0.018 2.25) Helplessness -4.44 (0.62) -3.69 (0.75) -0.75 (-2.73 to 0.455 1.23) SF-36 Summary Physical 10.85 (1.32) 6.84 (1.78) 4.01 (-0.36 to 8.38) 0.072 Mental 4.31 (1.38) 4.48 (1.83) -0.17 (-4.71 to 0.941 4.37) After adjusting for other relevant baseline variables, regression analysis indicated that higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PGA, while the number of drugs withdrawn and the time to withdrawal had lesser effects. The occurrence of minor side effects did not affect change in PROs (Table 2). Table 2: Relationship between drug-related toxicities and improvement in PROs over 3 years. Nature of toxicity FunctionPain Fatigue PGA Helplessness SF-36 SF-36 Physical Mental Frequency of β -0.02 -1.34 0.14 -0.98 -0.04 -0.13 -0.21 minor side SE 0.01 0.71 0.75 0.62 0.11 0.28 0.29 effects P-value 0.262 0.061 0.854 0.119 0.701 0.630 0.474 Frequency of β -0.07 -4.17 -3.47 -4.12 -0.34 -1.04 -0.32 withdrawals SE 0.03 1.32 1.38 1.13 0.22 0.52 0.56 P-value 0.005 0.002 0.013 8%), 64 had HBP (32 (50%) with BP>140/90 at the nurse visit), 60 had Dlp (24 (40%) with cholesterol >220mg/dL). 42 patients were active smokers and 48 were obese (BMI>30). In the patients without prior DM, the nurse clinic detected 4 patients (3/107, 4%) with glycemia ≥126mg/dL. In these patients a new blood test was ordered to confirm the diagnosis of DM. In patients without prior HBP 26 patients (26/69, 38%) had BP>140/90. In patients without prior Dlp 20 patients (18/73, 27%) had total cholesterol levels >220mg/dL and 37 (37/73, 51%) had LDL-cholesterol levels over their therapeutic target. Overall, this screening strategy allowed the detection of classical CVRF which were previously undetected or poorly controlled (DM, HBP, Dlp) in 105/133 (79%) of the evaluated patients. In all patients, the nurse-led educational program was initiated. Conclusion: A nurse led single-visit screening program allows the detection of classic CVRF in a high proportion of patients. If proper treatment for the classic CVF is initiated, this might result in a decrease of CV events with a favorable impact on the general health of chronic arthritis patients. Disclosure: N. Martínez-Alberola, None; F. Sivera, None; C. Fernández-Carballido, None; M. Andrés, None; R. Martín-Doménech, None; M. P. Martínez-Vidal, None; A. SanMartin-Alvarez, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/the-role-of-a-nurse-led-clinic-in-the-assessment-andprevention-of-cardio-vascular-risk
Abstract Number: 1495
Person-Centred Care Can Help Patients to Become More Effective Consumers in the Use of Health Information Than Regular Care – an RCT in Patients with Arthritis Undergoing Biological Therapy Ingrid Larsson1,2, Stefan Bergman2,3,4 and Ann Bremander2,3,5, 1School of Health and Welfare, Halmstad University, Halmstad, Sweden, 2FoU Spenshult, Halmstad, Sweden, 3Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, Lund, Sweden, 4Primary Health Care Unit, Department of Public Health and Community Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 5School of Business, Engineering and Science, Halmstad University, Halmstad, Sweden First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Quality Measures and Quality of Care Poster Session (ARHP): Clinical Practice/Patient Care Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose:
Person-centred care (PCC) is a holistic approach with respectful and individualized care allowing negotiation of care where persons with health problems are empowered to be involved in health decisions. Patients’ illness narratives constitute a starting point for building a collaboration with health care professionals and to empower them to play an active role in their health care. Little is known of the impact of PCC vs. regular care on patients’ skills as health care consumers. The aim was to study the impact on effective consumers’ skills over 6 and 12 months as measured by the Effective Consumer Scale (EC17) in patients undergoing biological therapy and randomly assigned to either a nurse-led rheumatology clinic (NLC) based on PCC or to a rheumatologist-led clinic (RLC) based on regular care. Methods: A 12 month RCT in 107 patients with chronic inflammatory arthritis1. Inclusion criteria were ongoing biological therapy and a DAS28 ≤3.2. All patients met a rheumatologist at inclusion and after 12 months, while the 6 month follow-up was randomized to either at an NLC (PCC) or at an RLC (regular care). Outcome measure was the EC17, developed and endorsed by the OMERACT, including five subscales; 1. Use of health information, 2. Clarifying personal priorities, 3. Communicating with others, 4. Negotiating roles and 5. Deciding and taking action. EC17 total score ranges from 0-100, worse to best. Differences between and within NLC and RLC were analyzed with Friedmans’ test or Mann Whitney U-test. Results: After 12 months 97 patients completed the RCT (NLC n=47, RLC n=50), mean (SD) age 55.4 (12.7) years, disease duration 16.7 (11.5) years, DAS28 2.1 (0.7), HAQ 0.54 (0.38), global health 20.4 (17.1), pain 21.1 (18.0) and 56% were women. There were no statistically significant differences within or between the two intervention groups at baseline nor in EC17 total score mean (SD) at baseline (NLC 83.5 (9.4) vs. RLC 83.2 (10.8), 6 months (NLC 85.4 (10.4) vs. RLC 82.9 (10.9) and 12 months (NLC 85.3 (11.1) vs. RLC 82.3 (10.9)). However, in NLC there was a statistically significant improvement in EC17 subscale “1. Use of health information” at both 6 and 12 months (p=0.041 and p=0.004 respectively). Conclusion: Replacing just one of three visits over 12 months to an NLC based on PCC instead of an RLC based on regular care resulted in more effective consumers concerning the use of health information. Larger studies over longer time frames focusing on PCC are needed to better understand its full impact on effective consumer skills measured by EC17. References: 1. Larsson I, et al. Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. J Adv Nurs 2014;70:164-75. Disclosure: I. Larsson, None; S. Bergman, None; A. Bremander, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/person-centred-care-can-help-patients-to-becomemore-effective-consumers-in-the-use-of-health-information-than-regular-care-an-rct-in-patients-with-arthritis-undergoing-biologicaltherapy
Abstract Number: 1496
Uncovering and Addressing Issues Related to Medication Adherence Among Patients with Rheumatic Diseases: A Patient Navigator Pilot Program Anarosa Campos1, Alyssa Wohlfahrt1, Yuanyu Lo1, Maura D. Iversen2, Elena Massarotti3, Daniel H. Solomon4 and Candace H. Feldman5, 1Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Northeastern University, Department of Physical Therapy, and Brigham & Women's Hospital, Harvard Medical School, Boston, MA, 3Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 4Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 5Rheumatology, Immunology and Allergy, Brigham and Women's Hospital,Harvard Medical School, Boston, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Quality Measures and Quality of Care Poster Session (ARHP): Clinical Practice/Patient Care Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM Background/Purpose: Poor adherence to medications is a common problem among rheumatology patients that can lead to irreversible negative outcomes. We piloted an intervention using patient navigators- laypeople trained in care coordination, basic rheumatology, and relevant pharmacology- to improve adherence to oral disease-modifying antirheumatic drugs (DMARDs). Navigators aimed to identify and understand barriers to adherence to DMARDs that may be missed during clinical encounters and to work with patients to develop personalized strategies to overcome these barriers. Methods: We recruited patients ≥18 years old from a large academic Arthritis Center. Eligibility included a rheumatic disease diagnosis by a board certified rheumatologist and initiation of an oral DMARD within the prior 6 months. Navigators conducted baseline interviews to assess patients' understanding of their rheumatic disease and their adherence to DMARDs. Then, depending on need, navigators contacted patients once every 1-4 weeks by phone or in person, and these conversations were thoroughly documented. Navigators connected patients with hospital resources, provided education about diagnoses and medications, and developed individually tailored strategies to circumvent barriers. Five team members independently reviewed the documentation from patient call notes to categorize issues raised by participants and subsequent navigator actions. Multiple issues and actions could be recorded per patient but each was counted only one time per patient. Differences in coding were adjudicated by the team. Results: Two navigators followed 88 patients for up to six months. Mean age was 54 years (SD 17) and 92% were female. 81% had inflammatory arthritis, 10% had lupus or mixed connective tissue disease, and 9% had other rheumatic diseases. Seven main categories of patient issues relevant to adherence were identified: adverse events (45%), challenges with medication acquisition (31%), concerns about medication effectiveness (30%), lack of knowledge about medications or diagnosis (20%), need for social support (14%), financial/insurance difficulties (11%), and interruptions in medication use (9%) (Table). 19% of patients raised no issues, 25% discussed one, and 56% ≥ 2 issues. The most common navigator actions included: facilitation of patient-doctor communication (33%), medication and diagnosis education (30%), development of individualized strategies to improve adherence (18%), and assistance with financial/insurance issues (11%) (Table). Conclusion: Most patients described one or more issues related to their oral DMARD adherence or to their rheumatic disease. Navigators played a key role uncovering and addressing concerns not identified by routine clinical care. Further analyses will assess the impact of navigators on DMARD adherence and rheumatic disease-related outcomes. Table. Patient issues and navigator actions related to medication adherence (N= 88) Categories of Patient Issues N (%) Adverse events (e.g. alopecia, rash, gastrointestinal side effects) 40 (45%) Challenges with medication acquisition (e.g. refills and prior authorizations) 27 (31%) Concerns about medication effectiveness (e.g. onset of action) 26 (30%) Lack of knowledge about medications or diagnosis 18 (20%) Need for social support (e.g. expression of depressive symptoms) 12 (14%) Financial/Insurance difficulties obtaining medications (e.g. high copayments, billing errors) 10 (11%) Interruptions in medication use (e.g. surgery, infections) 8 (9%) Navigator Actions N (%) Facilitation of patient-doctor communication (e.g. notified rheumatologists of patients symptoms or concerns) 29 (33%) Medication or diagnosis education (e.g. explained side effects, described expected timing of medication effects, helped manage side effects) 26 (30%) Development of individualized strategies to improve adherence (e.g. pillboxes, text messages, set-up of automatic refills, magnet reminders) 16 (18%) Assistance with financial and insurance issues (e.g. referral to financial counselor, interactions with insurance companies) 10 (11%) Coordination of care (e.g. helped patients obtain referrals to other specialties) 8 (9%) Provision of social and emotional support 7 (8%) Facilitation of expedited mental health referrals 6 (7%)
Disclosure: A. Campos, None; A. Wohlfahrt, None; Y. Lo, None; M. D. Iversen, None; E. Massarotti, None; D. H. Solomon, None; C. H. Feldman, Pfizer Inc, 2.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/uncovering-and-addressing-issues-related-tomedication-adherence-among-patients-with-rheumatic-diseases-a-patient-navigator-pilot-program
Abstract Number: 1497
Panlar Consensus on Hand, Hip and Knee OA Oscar Luis Rillo1, Humberto Riera2, Rolando Espinosa-Morales3, Carlota Acosta4, Veronica Liendo5, Joyce Bolaños6, Ligia Monterola7, Edgar Nieto8, Luisa M. Franco9, Rodolfo Arape10, Ana Antunez11, Silvia Beatriz Papasidero12, Mariflor Vera13, Jorge Esquivel14, Renee Souto15, Jose F. Molina16, César Rossi17, Francisco Ballesteros18, José Salas19, Francisco Radrigan20, Marlene GuibertToledano21, Gil Reyes Llerena22, Lorena Urioste23, Walter Camacho24, Abraham García25, Isa Iraheta26, Carmen E Gutierrez27, Raúl Aragón28, Margarita Duarte29, Oswaldo Castañeda30, Juan Angulo Solimano31, Ibsen Coimbra32, Roberto Munoz Louis33, Carlos Vallejo34, Ricardo Saenz35, Francisco Giron36, Anibal De León37, Ramon Perez Acuna38, Anthony M. Reginato39 and Maritza Quintero2, 1Hospital General de Agudos “Dr. Ignacio Pirovano”, Buenos Aires, Argentina, 2Unidad de Reumatología, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela, 3Mexican Board of Rheumatology, Mexico City, Mexico, 4Ciudad Bolivar, Hospital Universitario "Ruiz y Páez, Bolivar, Venezuela, 5Clínica Roosevelt, Caracas, Venezuela, 6Hospital Perez Carreño, Caracas, Venezuela, 7Clínica Colinas, Anzoátegui, Venezuela, 8Traumatology, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela, 9Instituto Docente de Urología, Carabobo, Venezuela, 10Centro Clínico La Isabelica, Carabobo, Venezuela, 11Hospital Central Dr. URQUINAONA, Maracaibo, Venezuela, 12Rheumatology Department, Hospital General de Agudos Dr. E. Tornú, Buenos Aires, Argentina, 13Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela, 14Universidad Autónoma de Nuevo León, Distrito Federal, Mexico, 15Catedra de Reumatología de la Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay, 16Centro Integral de Reumatologia Reumalab, Medellin, Colombia, 17Cátedra de Reumatología de la Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, 18Departamento de Reumatología, Universidad de Chile, Santiago, Chile, 19Reumacaribe, Barranquilla, Colombia, 20Departamento de Reumatología, Universidad Católica de Chile, Santiago, Chile, 21Rheumatology, Centro de Investigaciones Médico Quirúrgicas, Habana, Ciudad Habana, Cuba, 22Servicio Nacional de Reumatología, Centro de Investigaciones Médico Quirúrgicas (CIMEQ), La Habana, Cuba, 23Hospital Alfonzo Gumucio-Techo Académico Universidad Católica, San Pablo, Bolivia, 24Servicio de Medicina Interna, Hospital Obrero N° 3 de la Caja Nacional de Salud, Santa Cruz, Bolivia, 25Postgrado de Reumatología, Universidad Francisco Marroquí, Guatemala, Guatemala, 26Rheumatology, Guatemalan Association against Rheumatic Diseases (AGAR), Guatemala City, Guatemala, 27Instituto Salvadoreño del Seguro Social, San Miguel, El Salvador, 28FACULTAD DE MEDICINA, UNIVERSIDAD DE EL SALVADOR., San Salvador, El Salvador, 29Servicio de Reumatología, Hospital de Clínicas de Asunción, Universidad Nacional de Asunción, Asunción, Paraguay, 30Clínica Angloamericana, Lima, Peru, 31Rheumatology, Universidad Nacional Mayor San Marcos, Lima, Peru, 32Departamento de Clínica Médica, Faculdade de Ciências Médicas da UNICAMP, Campinas, Brazil, 33Reumatologia, Clinica Abreu - Hospital Docente Padre Billini, Santo Domingo, Dominican Republic, 34FACULTAD DE MEDICINA. PONTIFICIA UNIVERSIDAD CATOLICA DEL ECUADOR., Quito, Ecuador, 35Hospital Dr. Rafael A. Calderón Guardia, San José, Costa Rica, 36IHSS Tegucigalpa, Tegucigalpa, Honduras, 37Hospital Santo Tomás, Panama, Panama, 38Zona franca ultrpark 6A, Zona franca ultrpark 6A, La Aurora de Heredia, Costa Rica, 39Rheumatology, Rhode Island Hospital, The Warren Alpert School of Medicine at Brown University, Providence, RI First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Quality Measures and Quality of Care Poster Session (ARHP): Clinical Practice/Patient Care Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: The purpose of this Consensus is to update the PANLAR recommendations for hand, hip and knee osteoarthritis (OA) based on a combination of the available evidence and expert opinion. Methods: Recommendations were developed by a group of 40 specialists of 18 countries of Latin America, and patients suffering from OA of the referred joints. A systematic review of articles, meta-analysis and guidelines published between 2008 and January 2014 was undertaken. The level of evidence and degree of recommendation were classified according to the Center for Evidence Based Medicine at Oxford or Jadad scale. Level of agreement was established through a Delphi technique. Results: Both “strong” and “conditional” recommendations were made. In hand OA it is important to educate regarding joint protection
and to provide an exercise regimen that improves muscle strengthening and range of motion (IC). Topical NSAIDs are indicated in mild to moderate pain (IA). Acetaminophen (up to 3 g/day) is recommended as the oral analgesic of first choice (IA). If it is not effective, oral NSAIDs are recommended at the lowest effective dose and for the shortest time possible (IA). The use of chondroitin sulfate is recommended and may be used in the long-term (IA). The use of steroids or intra-articular hyaluronic acid might be considered for OA of the symptomatic TMC joint (IIaB). Surgery could be considered for severe rhizarthrosis in patients with strong pain and/or disability and after conservative treatment has failed (IIBB). For Hip OA, patients should be educated on the importance of changes in lifestyle (IB). Strengthening the extensors and abductors improves function and can prepare the patient before a hip implant (IB). In mild to moderate pain, acetaminophen (IB) is recommended. In cases of higher pain, high doses of NSAIDs or selective COX2 inhibitors could be indicated (IB). In patients who do not respond to NSAIDs or inhibitors of COX-2, or do not tolerate them or are contraindicated, weak opioids such as tramadol would be useful (IIbB). Total hip arthroplasty is indicated in patients with high pain, walking difficulty and loss of quality of life (IA). Finally in Knee OA, it is important to educate about lifestyle changes (IA). Acetaminophen is recommended up to 3 gr per day for mild pain (IA). For moderate pain, traditional and selective NSAIDs are indicated (IA). Topical NSAIDs may be indicated in patients with gastrointestinal risk (IA). In severe pain, the use of tramadol is recommended (IA).Treatment with chondroitin sulphate has demonstrated symptomatic effect in patients with knee OA and it may delay OA progression (IA). Combined use of glucosamine and chondroitin sulfate is indicated in patients with moderate to severe pain (IB). Benefits of intra-articular hyaluronic acid have been reported (IIaB). Arthroscopy is not beneficial (IIIA).Total knee arthroplasty may be indicated in knee OA (IIaB). Conclusion: These recommendations are based on the consensus judgment of clinical experts, informed by available evidence, balancing the benefits and harms of treatments, and incorporating their preferences and values. It is hoped that these recommendations will be useful in the management of OA patients. Disclosure: O. L. Rillo, None; H. Riera, None; R. Espinosa-Morales, None; C. Acosta, None; V. Liendo, None; J. Bolaños, None; L. Monterola, None; E. Nieto, None; L. M. Franco, None; R. Arape, None; A. Antunez, None; S. B. Papasidero, None; M. Vera, None; J. Esquivel, None; R. Souto, None; J. F. Molina, None; C. Rossi, None; F. Ballesteros, None; J. Salas, None; F. Radrigan, None; M. Guibert-Toledano, None; G. Reyes Llerena, None; L. Urioste, None; W. Camacho, None; A. García, None; I. Iraheta, None; C. E. Gutierrez, None; R. Aragón, None; M. Duarte, None; O. Castañeda, None; J. Angulo Solimano, None; I. Coimbra, None; R. Munoz Louis, None; C. Vallejo, None; R. Saenz, None; F. Giron, None; A. De León, None; R. Perez Acuna, None; A. M. Reginato, None; M. Quintero, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/panlar-consensus-on-hand-hip-and-knee-oa
Abstract Number: 1498
Engaging Clinic Staff in Work System Redesign to Adapt a Hypertension Protocol for Rheumatology Edmond Ramly1, Diane Lauver2 and Christie M. Bartels3, 1Industrial and Systems Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI, 2University of Wisconsin-Madison School of Nursing, Madison, WI, 3Department of Medicine, University of Wisconsin (UW) School of Medicine and Public Health (SMPH), Madison, WI First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Quality Measures and Quality of Care Poster Session (ARHP): Clinical Practice/Patient Care Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Despite routine blood pressure (BP) measurement by clinic staff, we reported that rheumatologists discussed elevated BPs in 0.05). Conclusion: Patients with RA had significantly lower estimated sodium:potassium intake ratio than control subjects. Higher 24 hour potassium intake was significantly associated with lower DBP in patients with RA. Further studies are needed to evaluate the impact of diets with low sodium and high potassium content on blood pressure in patients with RA.
Grants: P60AR056116, K23AR064768, KL2TR000446, GM5M01-RR00095, UL1 RR024975-01, and 2 UL1 TR000445-06 from the NIH, and a grant from Alpha Omicron Pi Disclosure: C. P. Chung, NIH, 2; M. J. Ormseth, None; A. M. Oeser, None; J. F. Solus, None; C. Okafor, None; J. Titze, None; Y. Zhang, None; C. M. Stein, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relationship-between-estimated-sodium-and-potassium-intake-withblood-pressure-and-inflammatory-markers-in-patients-with-rheumatoid-arthritis
Abstract Number: 1519
Pleuropulmonary Manifestations in Rheumatoid Arthritis Patients Suzan Attar1 and Omar Amoudi2, 1Internal Medicine, MBBCH. FRCPC. ABIM, Jeddah, Saudi Arabia, 2Internal Medicine, FRCPC, Jeddah, Saudi Arabia First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Pulmonary involvement in rheumatoid arthritis (RA) patients is associated with high morbidity and mortality. Nevertheless, limited data are available regarding such lung complications in the Middle East, especially in the Kingdome of Saudi Arabia. The objective of the current study were to determine the prevalence of pleuropulmonary manifestations and to identify the risk factors predicting lung involvement. Methods: This was a retrospective study involving 419 RA patients diagnosed at a tertiary center over a 12.5-year period. RA was diagnosed on the 2010 American College of Rheumatology (ACR) criteria. The frequency of pulmonary manifestations were recorded based on combined results from the chest Xrays, pulmonary function tests, and high resolution computed tomography (HRCT) scan on the chest. Results: The overall frequency of lung involvement in RA was 25.8%. Pneumonia and bronchiectasis were the most common abnormalities (36% and 35% respectively). HRCT scan was more sensitive in detecting of pleuropulmonary abnormalities. . The presence of comorbid illness (OR=3.19, 95% CI: 2.02– 5.1), male gender (OR=2.4, 95% CI: 1.3–4.24), and the presence of extra-articular manifestations (OR=2.35, 95% CI: 0.4–4.01) were significantly predicting lung involvement . Conclusion: Pneumonia and bronchiactasis were the most common abnormalities seen in RA patients in Saudi Arabia. This finding were comparable with other studies.. The presence of comorbidity , male gender and extra-articular manifestation were statistically associated with lung involvement .
Disclosure: S. Attar, None; O. Amoudi, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/pleuropulmonary-manifestations-in-rheumatoid-arthritis-patients
Abstract Number: 1520
Safety, Clinical and Immunologic Effectiveness of the Live Zoster Vaccine Administered to Patients Receiving Anti-TNF Biologics Jeffrey R. Curtis1,2, Anita Turner3, Corretta Thomas4, Stacey Cofield4, Randall Parks5, Jennifer H. Ku6, Ilhem Messaoudi- Powers7, Keith Wanzeck1 and Kevin L. Winthrop8, 1University of Alabama at Birmingham, Birmingham, AL, 2Rheumatology & Immunology, University of Alabama-Birmingham, Birmingham, AL, 3Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 4School of Public Health, University of Alabama at Birmingham, Birmingham, AL, 5Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 6Casey Eye Institute, Oregon Health & Science Univ, Portland, OR, 7Oregon Health and Sciences University, Portland, OR, 8Oregon Health & Science University, Portland, OR First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: The live herpes zoster vaccine (ZV) has been shown to be safe and effective in large randomized controlled trials of older adults. It is currently contraindicated in participants receiving immunomodulatory therapies such as biologic agents due to theoretical concerns regarding safety. Methods: VERVE is a 2-site, pilot study (n=125 participants) preparatory to a large NIH-funded pragmatic randomized controlled trial (RCT) of 1,000 participants
receiving anti-TNF therapy. Participants must be age >= 50 years, receiving any FDA-approved anti-TNF therapy for rheumatoid arthritis (RA), psoriatic arthritis (PsA) or other spondyloarthritis. Participants were randomized to ZV or blinded placebo. The primary outcome was immunogenicity at 6 weeks; secondary outcomes included clinical safety, tolerability, and long-term clinical effectiveness. For the pilot study, participants must also not have received glucocorticoid therapy within the past month. Results of this ongoing trial have not yet been unblinded. Therefore only baseline characteristics at the time of this abstract were available, presented as mean(SD) or %, as applicable. Results: A total of 95 participants have been screened for VERVE as of June 2015. Of these, 19 have been randomized (20.0%); 3(3.2%) tested negative on screening varicella ELISA testing and were considered screen failures; 73 (76.8%) have been enrolled and are awaiting randomization. Characteristics of the 19 randomized participants included age 60(7) years, 68.4% women, 73.7% with RA, 15.8% PsA. The most commonly used concomitant DMARD therapies were methotrexate (85.7%) and hydroxychloroquine (7.1%). Concomitant biologics included adalimumab (47.1%), etanercept (23.5%), Infliximab (17.6%), and golimumab (11.8%). The majority of participants had moderate disease activity (42.1%), with mean CDAI of 13.7(10.6). Among the 19 randomized who received ZV or placebo, there were no clinically significant serious adverse events attributable to the vaccine in the 40(16) days of followup (5.7 weeks; range 2.3, 9.0). Conclusion: Preliminary results from VERVE have shown no immediate safety-related issues when given to patients with autoimmune diseases being actively treated with anti-TNF biologic agents. Ongoing results for the entirety of the pilot study are expected by Nov. 2015 to further characterize the immunogenicity and effectiveness of the vaccine in abti-TNF users. Disclosure: J. R. Curtis, Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 2,Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 5; A. Turner, None; C. Thomas, None; S. Cofield, None; R. Parks, None; J. H. Ku, None; I. Messaoudi- Powers, None; K. Wanzeck, None; K. L. Winthrop, BMS, 2,AbbVie, BMS, UCB, Amgen, 5. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/safety-clinical-and-immunologic-effectiveness-of-the-live-zostervaccine-administered-to-patients-receiving-anti-tnf-biologics
Abstract Number: 1521
Screening for Urinary Tract Infection in Rheumatoid Arthritis Patients Treated with TNFInhibitors in the Daily Clinic Renata Baronaite Hansen1, Anne Brun Hesselvig2, Rolf Magnus Arpi2, Eva Kristin Jonassen1, Gunhild Bukh1 and Ole Rintek Madsen1, 1Department of Rheumatology/C, Department of Rheumatology/C, Copenhagen University Hospital Gentofte, Hellerup, Denmark, 2Department of Clinical Microbiology, Department of Clinical Microbiology, Copenhagen University Hospital Herlev, Herlev, Denmark First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Patients with rheumatoid arthritis (RA) treated with biologic agents are at increased risk of infection. Therefore, screening for urinary tract infection (UTI) with urine dipsticks (UD) is often performed as part of monitoring in the daily clinic regardless of UTI symptoms. We examined the prevalence of bacteriuria detected by UD and urine culture (UC), and the value of UD compared to UC in TNFi-treated RA patients. Secondary aims were to assess the reproducibility of UD and the association between UTI symptoms and results of UD and UC. Methods: Urine samples from 126 adult RA patients treated with TNFi for ³ 6 months were collected according to standard guidelines and tested twice by use of an automated UD test (Clinitek) (one patient had only one UD performed), followed by quantitative UC. Positive UD test was defined as presence of leucocyte esterase and/or nitrite. UC with more than 100,000 CFU/mL was considered positive. True and false positive and negative rates (TPR, FPR, TNR and FNR) and positive and negative predictive values (PPV and NPV) were calculated. Cross-tabulations and X2-tests were used to analyze the results. Results: Patient characteristics are shown in Table 1 and urine test results in Table 2 and 3. Only one patient (0.8%) had UTI symptoms (UD negative). 4.8% (n = 6) of the patients had a positive UC. None of these had UTI symptoms and only 50% (n = 3) were UD positive (dipstick 1, 2 or both). In the patients as a whole (n = 126), UD was positive in 23% of the cases but only 10.3% (PPV) of these had a positive UC. The NPV for UD was 96.9% versus 95.2% for UTI symptoms. Duplicate UD results agreed (positive or negative) in 97.6% of the cases indicating high reproducibility. Conclusion: Less than 5% of RA patients treated with TNFi had a positive UC, none of these had UTI symptoms and UD detected only half of the cases. The PPV for UD was only 10%. The NPV for UD was high, reflecting the low prevalence of positive UC in the study population. The results question the value of general UTI screening with UD and/or UC in the daily clinic. Table 1. Basic characteristics of 126 RA patients.
Male:female ratio 1:3 Age at diagnosis (yrs), mean/SD (range) 44/14.13 (11.1-76.8) Time since diagnosis (yrs), mean/SD (range) 15.1/10.7 (1.4-43.9) Length of treatment with TNFi (yrs), mean/SD (range) 4.5/3.4 (0.1-12.9) Positive RF and/or anti-CCP, n /% 84/67 (unknown in 7) Erosive disease, n /% 69/55 Concomitant DMARDs, n /% 102/81 DAS28-CRP, mean/SD (range) 2.64/0.97 (1.2-6.5) HAQ-DI, mean/SD (range) 0.78/0.65 (0-2.88) Table 2. Urine dipstick (UD) compared with urine culture (UC). UD pos UD neg Totals UC 3 3 6 pos UC 26 94 120 neg Totals 29 97 126 PPV=10.3; NPV=96.9; TPR=50; TNR=78.3; FPR =21.6; FNR=50.0 [all in %]; X2=2.6, p= 0.11 Table 3. Urinary tract infection (UTI) symptoms compared with urine culture (UC). +UTI symp.
- UTI symp.
UC 0 6 6 pos UC 1 119 120 neg Totals 1 125 126 PPV= 0; NPV=95.2; TPR=0; TNR=99.2; FPR=0.8; FNR=100 [all in %]; X2 =0.05, p=0.82 Disclosure: R. Baronaite Hansen, None; A. Brun Hesselvig, None; R. M. Arpi, None; E. K. Jonassen, None; G. Bukh, None; O. Rintek Madsen, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/screening-for-urinary-tract-infection-in-rheumatoid-arthritis-patientstreated-with-tnf-inhibitors-in-the-daily-clinic
Abstract Number: 1522
Correlation of Oxidized Low Density Lipoprotein Levels with Carotid Intima Media Thickness in Rheumatoid Arthritis Patients GHAN SHYAM PANGTEY1, SANJAY PARMAR1, RITU SINGH2 and RAMA ANAND3, 1DEPARTMENT OF MEDICINE, LADY HARDINGE MEDICAL COLLEGE, New Delhi, India, 2BIOCHEMISTRY, LADY HARDINGE MEDICAL COLLEGE, New Delhi, India, 3DEAPRTMENT OF RADIOLOGY, LADY HARDINGE MEDICAL COLLEGE, DELHI, India First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Rheumatoid Arthritis (RA) patients are more prone to atherosclerosis. Oxidation of Low-density lipoprotein (LDL) is an important event in the development of atherosclerosis, especially of coronary and carotid arteries. We hypothesized that due to increased systemic inflammatory response in RA patients there will be higher subclinical/ clinical morphologic evidence of atherosclerosis in carotid arteries, leading to increased carotid intima media thickness (IMT). Our primary objective was to correlate serum Oxidized LDL level with Carotid IMT in RA patients; secondary objective was to correlate oxidized LDL
with disease activity by DAS 28. Methods: This descriptive observational case control study recruited 30 RA patients (1987 ACR criteria) without any comorbidities (diabetes mellitus, hypothyroidism, morbid obesity, dyslipidemia, chronic kidney disease, chronic liver disease, or known atherosclerotic disease) and 30 age and sex matched healthy controls; active smokers and non consenting participants were excluded. After history, examination and routine laboratory investigations, oxidized LDL levels were obtained by ELISA method. Carotid IMT was measured by Doppler ultrasonography (Philips HDI5000): Common carotid IMT (CCIMT), carotid bulb IMT (CBIMT), total carotid IMT (TCIMT), and internal carotid IMT (ICIMT) were measured by trainned radiologist. Means were compared using unpaired "t" test; correlation was measured using Pearson correlation method. SPSS version 19 was used for statistical analysis, and p5.1), while in 3 cases it was found that disease activity was in moderate range (3.2-5.1). Values of CCIMT, CBIMT, and TCIMT were significantly higher in RA patients (p65 years; p=0.073), lower eGFR (0.6), and calculated a risk score by weighting alleles by their published log-odds, standardizing the sum against an RA-free population. The association of RA risk score, individual SNPs, and the shared epitope alleles, with DAS28-based EULAR response at the evaluation visit closest to 3 months after initiation, was estimated using logistic regression models. Results: With respect to RA risk, the genetic risk score was a stronger predictor of onset of ACPA+ than ACPA- RA (odds ratio per stdev increase: 2.2 vs 1.2). With respect to response to methotrexate, the number of SNPs associated to EULAR response in individual analyses was not higher than expected by chance (3/76 SNPs had p2.8 to ≤10); or incomplete-responders (CDAI ˃10). Outcomes included the proportion of patients with no radiographic progression (change in modified Total Sharp Score [mTSS] ≤0) and/or HAQ-Disability Index (HAQ-DI) 33%) in the second cycle were more likely to be responders than others (11 of 11 versus 11 of 21). Interestingly, 80 % of these patients became responders and had greater CD4+ depletion in cycle 2 than in cycle 1. Conclusion: Repeated post-treatment CD4+ T-cell depletion occur over successive cycles of RTX in RA patients. These results suggest that CD4+ T-cell variations induced by RTX are more closely related to changes in disease activity than B-cell variations. Monitoring circulating CD4+ T-cells might be helpful for clinicians when assessing disease activity and also for consequent evaluation of treatment efficacy or for the determination of re-treatment intervals in RTX-treated RA patients. Disclosure: M. Lavielle, None; D. Mulleman, None; H. C. Sung, None; C. Bahuaud, None; P. Goupille, None; H. Watier, None; G. Thibault, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/repeated-cd4-t-cell-depletion-in-patients-with-rheumatoid-arthritis-overmultiple-cycles-of-rituximab-treatment
Abstract Number: 1657
Evaluation of Bone and Joint Proteins for Prognostic Association with Radiographic Progression and Disease Activity in Methotrexate Inadequate Responder Rheumatoid Arthritis Patients in a Sarilumab Phase 3 Study Anita Boyapati1, Jérôme Msihid2, Jennifer D Hamilton1, Cem Gabay3, Neil Graham1 and Stefano Fiore4, 1Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 2Sanofi R&D, France, Chilly-Mazarin, NJ, France, 3Rheumatology, Geneva University Hospital, Geneva, Switzerland, 4Sanofi, Bridgewater, NJ First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: In patients with early RA, autoantibodies, elevated MMP-3, and acute phase proteins are prognostic biomarkers of joint damage and disease activity. However, the ability to identify patients most likely to have progressive disease is limited in those with established RA. The MOBILITY study (NCT01061736) included MTX inadequate responder (MTX-IR) RA patients. Two doses of sarilumab (SAR) studied (200 mg every 2 wks [q2w] and 150 mg q2w) + MTX significantly reduced radiographic joint damage compared with placebo (Pbo) + MTX, including modified total Sharp score (mTSS), erosion score (ES), and joint space narrowing (JSN). Mean change from baseline in mTSS at wk 52 was 0.90 and 0.25 for SAR 150 mg and 200 mg + MTX, respectively, and 2.78 for Pbo + MTX (P3.2, BASDAI>4, BASFI>4, PSAID>4, HAQ>0.5, SJC≥1, TJC≥1, for PtGA/BASDAI/BASFI/Fatigue/Pain>40 mm, ESR and CRP>ULN. Results: There were 655 RA (79.1%F), 624 AS (33.5% F) and 161 PsA (65.8%F), patients. Mean(SD) age was 52.8 (12.5) 41.8 (11.4) and 44.8 (11.8) years. Mean(SD) disease duration was 11.5 (8.0), 10.1(7.5) and 10.3(7.3) years. In RA, AS and PsA mean(SD) BMI was 29.1 (5.9), 27.2 (5.4), 28.7 (6.1); and %BMI>30 were 40.2, 24.5 and 37.3. Disease activity groups by BMI categories are shown in Table. Conclusion: In these cross sectional view, obese RA (DAS-28, all PROs, acute phase reactants) and PsA (BASDAI, PsAID, pain) patients had more active state, however obesity did not influence on activity of AS patients. Functional impairment of obese patients may be related mechanical effect of weight rather than disease activity. For each disease, different influence of BMI on disease activities need to assess at other biological registries. References: 1.
Sandberg ME et al. Ann Rheum Dis. 2014;73:2029-33.
Durcan L et al. J Rheumatol. 2012;39:2310-4.
Eder L et al. Ann Rheum Dis. 2015;74:813-7.
Table. Disease activity and patient reported measures by BMI categories
Measures DAS-28 > 3.2
Diagnosis RA AS n (%) PsA BASDAI > 4 RA AS n (%) PsA BASFI>4 RA AS n (%) PsA PsAID>4 RA AS n (%) PsA HAQ > 0.5 RA AS n (%) PsA SJC ≥ 1 RA AS n (%) PsA TJC ≥ 1 RA AS n (%) PsA PtGA > 40 mm RA AS n (%) PsA Pain > 40 mm RA AS n (%) PsA Fatigue > 40 RA mm AS PsA n (%) CRP > ULN RA AS n (%) PsA ESR > ULN RA AS n (%) PsA
BMI≥30 BMI0.5cm, and sacral sclerosis >0.3cm. Inter-reader reliability for these variables were 1.0 for ankylosis, 0.99 for number of iliac erosions, 0.99 for number of sacral erosions, 0.58 for iliac sclerosis, and 0.39 for sacral sclerosis. Fig 1A demonstrates the ROC curves for the total erosion number as well as the increasing depth of sclerosis. A total erosion number of ≥3 erosions was found to have the highest sensitivity and specificity for AS. Fig 1B demonstrates the ROC curves for combinations of ankylosis, sclerosis, and erosions for diagnosing AS. Sclerosis was defined as either >0.5cm of iliac or >0.3cm of sacral sclerosis >1cm in length. The presence of >1cm of ankylosis or ≥3 total erosions resulted in a sensitivity of 91% and specificity of 91%. The addition of >0.5cm of iliac sclerosis or >0.3cm of sacral sclerosis marginally increased the sensitivity to 94% but decreased specificity to 86%. Conclusion: It is proposed that the presence of ankylosis >1cm or ≥3 total erosions has the greatest diagnostic utility for AS.
Disclosure: J. Chan, None; I. Sari, None; D. Salonen, None; R. D. Inman, None; N. Haroon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/development-of-a-novel-si-joint-ct-score-for-diagnosis-of-axialspondylitis
Abstract Number: 1713
Fat Metaplasia on Sacroiliac Joint Magnetic Resonance Imaging at Baseline Is Associated with Spinal Radiographic Progression in Patients with Axial Spondyloarthritis Kwi Young Kang1, In Je Kim2, Yeon Sik Hong3, Sung-Hwan Park4 and Ji Hyeon Ju5, 1#505, Banpo-dong, Seocho-gu, Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, Seoul, South Korea, 2Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea, 3catholic University of Korea, Incheon, South Korea, 4Kangnam St Mary's Hospital, Seoul, South Korea, 5Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Spondylarthropathies and Psoriatic Arthritis - Comorbidities and Treatment Poster II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: To study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA). Methods: One hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression. Results: Among the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p6mg/L or presence of MRI inflammatory signals at the spine or sacro-iliac joint level) in the 2-year abdominal fat mass changes. Results: A total of 129 patients of the DESIR cohort (71 men (55.0%), mean age of 33.0 (±8.6) years old) with a mean disease duration of 17.9 (±10.7) months, were included. Their mean body mass index was 23.7 (±3.5) kg/m2 and the prevalence of obesity (BMI>30 kg/m²) was 6.2%. We did not find any significant changes of SAT over 2 years; VAT tended to increase over 2 years from baseline of 7.3% (±28%) (p= 0.054). 2-year VAT changes was significantly associated with the presence of the baseline ASAS criteria fulfillment (p=0.015), hypercholesterolemia at baseline (p=0.007), hypertriglyceridemia at baseline (p=0.0026) and 2-year changes in BMI (p/=30) plaque CCTA: (yes/no) new plaque (yes/no) No No Yes Yes No No Yes Yes No Yes Yes No No Yes Yes No No Yes Yes No No No Yes No No No No No Yes Yes Yes No No Yes Yes No No Yes Yes Yes Yes
Diabetes Depression Current Current Smoking steroid HRT history therapy
Yes No Yes No No No No
Yes No Yes Yes Yes No Yes
Yes No Yes Yes No No No
No Yes No Yes Yes No No
Yes Yes Yes Yes No No No
BMI: body mass index (kg/m2), HLD: hyperlipidemia, defined by total cholesterol >200mg/dL, HRT: hormone-replacement therapy * Small subendocardial infarction with significant stenosis
Disclosure: V. K. Sandhu, None; M. L. Ishimori, None; J. Wei, None; L. Thomson, None; D. Berman, None; J. Schapira, None; N. Bairey Merz, None; D. Wallace, None; M. Weisman, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/a-five-year-follow-up-of-microvascular-dysfunction-and-coronaryartery-disease-in-sle-results-from-a-community-based-lupus-cohort
Abstract Number: 1811
Depression and Progression of Subclinical Cardiovascular Disease in Systemic Lupus Erythematosus April Jorge 1, Apinya Lertratanakul2, Julia (Jungwha) Lee3, William Pearce1, David McPherson4, Trina Thompson5, Emma Barinas-Mitchell6 and Rosalind Ramsey-Goldman1, 1Northwestern University Feinberg School of Medicine, Chicago, IL, 2Northwestern University, Chicago, IL, 3Department of Preventive Medicine, Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 4University of Texas Health Science Center, Houston, TX, 5Saint Francis University, Ebensburg, PA, 6University of Pittsburgh, Pittsburgh, PA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Women with SLE have an increased incidence of premature cardiovascular disease (CVD). Depression is also common among SLE patients. A relationship between depression and increased inflammation leading to CVD has been proposed. The aim of this study was to evaluate the relationship between depression and the progression of subclinical CVD in women with SLE. Methods: In a prospective case-control study, the Study of Lupus Vascular and Bone Long-term Endpoints (SOLVABLE), there were 185 women with SLE meeting ACR revised classification criteria and 186 controls. Participants were evaluated at baseline and 5 years, including demographic data, laboratory studies, CVD risk factors, depression screening with the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire, ultrasound evaluations of carotid artery intima-media thickness (IMT) and carotid plaque, and assessment of SLE disease activity and damage for the SLE cases. Depression was defined as CES-D score > or = 16. Plaque progression was defined by an increase in number of plaques over 5 years. IMT progression was defined as increase in IMT over 5 years. HTN was defined as systolic blood pressure (BP) >140mmHg, diastolic BP >90mmHg, or taking anti-hypertensive medication. Descriptive statistics were calculated for baseline variables. Logistic regression was used to evaluate the association between baseline
depression and the progression of carotid plaque. Linear regression was used for baseline depression and progression of IMT. Results: A total of 149 participants with SLE and 126 controls completed follow-up over 5 years. The SLE group was younger (48.6 years vs. 52.2, p=0.003) and had more hypertension (HTN) (57.7% vs. 31.8%, pHCQ>CQ>PQ) to inhibit cGAS activity, validating the prediction of our computational analysis. EMSA revealed that AMD disrupted the double stranded DNA-cGAS complex in a dose dependent manner, indicating that AMD blocked dsDNA/cGAS binding. These AMD also inhibited IFN-I expression in THP1 cells transfected with dsDNA and in 293T cells transfected with cGAS/STING plasmids validating that cGAS is a target of AMD. Based on these results and in silico modeling, we synthesized several new AMD. One of these compounds, X6, had excellent water solubility and cell penetration. Fluorescence microscopy revealed that X6 localized to the cytosol and had a lower toxicity profile compared to QC. In vitro and cell based studies, revealed that X6 was a more potent inhibitor of IFN-I production following dsDNA transfection into reporter cells than HCQ. X6 was also more potent than HCQ in the inhibition of IFN-a production following CpGA stimulation of PBMC.
Conclusion: Our studies identify the cytosolic DNA sensor, cGAS, as a target of AMD activity, which provide a novel mechanism of action of these AMD. This observation together with decades of experience of AMD in human diseases, suggest that this widely used family of drugs with a strong safety profile could be repurposed to target interferonopathies and possibly other autoimmune disorders related to cGAS over-activity. Disclosure: J. An, None; J. Woodward, None; M. Minie, None; Y. Peng, None; T. Sasaki, None; K. B. Elkon, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/novel-mechanism-of-action-of-anti-malarial-drugs-in-the-inhibition-oftype-i-interferon-production
Abstract Number: 1814
Efficacy of Isoniazid Chemoprophylaxis in Lupus Nephritis Patients Jin Young Moon, Hyun Mi Kwon, Eun Young Ahn, Jin Kyun Park, Yeong Wook Song and Eun Bong Lee, Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Treatment of lupus nephritis requires aggressive immunosuppressive drugs which includes high dose glucocorticoids. Immunosuppressive treatment is a risk factor for opportunistic infections such as mycobacterium tuberculosis (Tbc). However, the efficacy of isoniazid (INH) chemoprophylaxis has not been evaluated in lupus nephritis patients. The aim of this study was to investigate the preventive effect of INH chemoprophylaxis on incidence of Tbc infection in patients with lupus nephritis on immunosuppressive treatment. Methods: In this retrospective cohort study, 332 patients with lupus nephritis were enrolled, who received glucocorticoids and immunosuppressive treatment at Seoul National University Hospital between 2004 and 2015. Information on baseline clinical characteristics and treatment were obtained from electronic medical record review. Incidence rates of Tbc were compared between patients who took INH prophylaxis (prophylaxis group) and those who did not (non-prophylaxis group), using log-rank test. Then, incidence rates of Tbc were investigated in subgroups of patients; those who received prednisolone >= 60 mg/day and high dose glucocorticoid pulse therapy. Results: A total of 332 patients with lupus nephritis were identified during the study period. The mean age was 35.3 ± 14.8 years and 266 (80.1%) were female. Among 332 patients, sixty-nine (20.8%) patients received INH prophylaxis and 263 (79.2%) patients did not. No case of Tbc developed in 69 patients of INH prophylaxis group while 9 cases of Tbc developed in 263 patients of non-prophylaxis group (0.0/100 person-years (PY) vs 0.53/100 PYs, p=0.236, by log-rank test). INH prophylaxis was effective neither in high dose (>= 60 mg/day or its equivalents) prednisolone group (0.00/100 PYs vs 0.58/100 PYs, p=0.288, by log-rank test), nor in patients who received glucocorticoid pulse therapy (0.00/100 PYs vs 0.69/100 PYs, p=0.161, by log-rank test). No patient died of Tbc infection. Conclusion: In this retrospective review, INH chemoprophylaxis did not lead to statistically significant prevention of Tbc in lupus nephritis patients. Table 1. Isoniazid chemoprophylaxis in patients with lupus nephritis
Prophylaxis Age, mean ± SD years Female sex (%) Follow up duration, mean ± SD years Prednisolone >= 60 mg/day (%) Steroid cumulative dose, mean ± SD mg Steroid pulse (%) Rituximab (%) Mycophenolate mofetil (%) Tacrolimus (%) Cyclophosphamide (%) Mycobacterium tuberculosis IR,
(n = 69) 37.78±13.47 55 (79.7)
Non-prophylaxis (n = 263) 34.60±15.07 211 (80.2)
p-value 0.092 0.924
7.5 mg/day along with an ISM other than hydroxychloroquine. Descriptive statistics were obtained. Chi square test were used to compare discrete variables, while t tests were used to compare continuous variables. Mann –Whitney test was used when data was not normally distributed. P value < 0.05 was considered significant on two tailed tests. Results: 86% were women and the mean (SD) age was 27.9 ± 4 years. Forty one percent of patients were taking one ISM, 41% were on two and 19% were on three ISMs'. Nearly half of the patients were on CS with a median dose of 5 mg/day. Hepatitis B & C screening tests were performed in 34% and 33% patients respectively. All the patients tested for Hepatitis B Surface Antigen (HBS Ag) were negative. Of those tested, 12/29 had Hepatitis B Surface Antibody (HBS Ab), 2/29 Hepatitis B core Antibody (HBc Ab) & 1/33 had Hepatitis C antibody (HCV Ab). Screening tests were offered more frequently to younger patients, those on more than one ISM, those on CS and those on significant ISM. Among those on significant ISM, 47% were screened for HBS Ag, as compared to 22% of patients not on significant ISM (p=0.007). Likewise, 47% on significant ISM were screened for HCV Ab as compared to 20% not on significant ISM (p=0.004). Conclusion: Less than 40% of those on ISM received Hepatitis B & C screening in SLE. Less than half of SLE patients that were tested prior to ISM showed immunity against Hepatitis B virus. Nearly 7% of SLE patients tested for Hepatitis B before ISM, showed chronic Hepatitis B, while 3% of SLE patients tested positive for Hepatitis C virus before ISM. These results indicate opportunities to improve screening and detect Hepatitis B/C in SLE patients on ISM. Education of physicians treating patients at higher risk and harmonization of various recommendations on Hepatitis B and C screening is indicated.
Disclosure: C. Annem, None; J. A. Block, Gilead, Inc, 1,Novartis, Genentech, Hoffman-LaRoche, Abbvie, Pfizer, Forest Research Institute, GlaxoSmithKline, 2,Roche Pharmaceuticals, 5,Novartis, Genentech, Hoffman-LaRoche, Abbvie, Pfizer, Forest Research Institute, Glaxo-SmithKline, 7,inPractice Resources LLC (Textbook Chapter) American Physician Institute, Inc (Board Review Lectures), 9; M. Jolly, Pfizer Inc, 7. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/how-good-a-job-are-we-rheumatologists-doing-in-screening-forhepatitis-b-and-c-before-immuno-suppressives-initiation-in-sle
Abstract Number: 1841
Meningitis in Systemic Lupus Erythematosus Patients: Epidemiologic Profile of Listeria Monocytogenes Infection. a Single-Center Study Ana Barrera-Vargas1, Javier Merayo-Chalico2, Armelle Pérez Cortés Villalobos3, Alfredo Ponce de León3, Jorge Alcocer-Varela1 and Diana GómezMartín1, 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 2Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 3Department of Infectology and Microbiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Infections are an important cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. These patients are more prone to develop infections, both because of intrinsic immune system abnormalities associated with the disease and immunosuppressive therapy. Listeria monocytogenes is a foodborne pathogen that may cause invasive disease, including bacteremia and meningitis, in immunocompromised patients. The aim of this study was to address characteristics and risk factors associated with meningitis by L. monocytogenes and to compare them with meningitis caused by other bacteria in SLE patients. Methods: We performed a retrospective cohort study in a tertiary care center in Mexico City between 2000 and 2015. SLE patients who had a cerebrospinal fluid (CSF) culture positive for L. monocytogenes or other gram-positive bacteria were included. All patients fulfilled at least 4 ACR criteria for SLE. We also analyzed patients without SLE with a positive CSF culture for L. monocytogenes. Patients with a clinical diagnosis of meningitis but without a positive CSF culture were excluded. Demographic, clinical and serologic features both 3 months before and at the infection were recorded. Results: Fourteen patients had a positive CSF culture for L. monocytogenes during the study period, and 9 of them (64%) had SLE. Among all SLE patients with meningitis proven by a positive CSF culture (n=22), infection with L. monocytogenes represented 41%. Group B streptococcus and S. pneumoniae were the second most common pathogens, each accounting for 14%. There was no difference in SLEDAI score, complement and anti-dsDNA levels 3 months prior to the infection between both SLE groups. Prednisone and azathioprine dose 3 months before the infection were higher in patients with L. monocytogenes meningitis (p=0.025 and 0.043, respectively). At the time of the infection, there was no difference in complement and antidsDNA levels; SLEDAI and SDI scores; prednisone, immunosuppressive and antimalarial drug dose; and CSF findings between both groups. Most SLE patients with L. monocytogenes received ampicillin (89%) during the first 24 hours after admission. SLE patients with L. monocytogenes had shorter stays in an intensive care unit (p=0.034) and lower mortality at 6 months (11 vs 54%, p=0.04) than those with meningitis by other bacteria. There was also a trend for lower mortality in patients with L. monocytogenes meningitis and SLE compared to those without SLE (11 vs 60%, p=0.052). Conclusion: This is the largest, single-center study regarding L. monocytogenes meningitis in SLE patients. L. monocytogenes was a common cause for meningitis in our cohort, and SLE patients seemed especially susceptible to this pathogen. Other immunosupressed patients (HIV, transplant recipients, chemotherapy, other rheumatologic diseases) are routinely treated at our institution and the incidence in those patients was clearly lower. Whether a specific immunologic defect predisposes SLE patients to L. monocytogenes remains to be determined. On the other hand, mortality and days in an intensive care unit were lower in SLE patients with L. monocytogenes, which could be related to the prompt initiation of appropriate antibiotic therapy. Disclosure: A. Barrera-Vargas, None; J. Merayo-Chalico, None; A. Pérez Cortés Villalobos, None; A. Ponce de León, None; J. Alcocer-Varela, None; D. Gómez-Martín, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/meningitis-in-systemic-lupus-erythematosus-patients-epidemiologicprofile-of-listeria-monocytogenes-infection-a-single-center-study
Abstract Number: 1842
Systemic Lupus Erythematosus and Chikungunya Fever: Interactions during the 2014 Outbreak in Martinique Bastien Bigeard1, Katlyne Polomat2, Emilie Javelle3, Serge ARFI2, Lauren Brunier-Agot4, Florence MOINET2, Fatiha Najioullah5, Elodie Curlier6, Andre Cabié7, Michel DeBandt1, Georges Jean Baptiste2 and Christophe Deligny2, 1internal medicine and rheumatology, Zobda Quitman Hospital, Fort de France, Martinique, 2Rheumatology and Internal Medicine, Zobda Quitman Hospital, Fort de France, Martinique, 3Tropical and Infectious Diseases, Laveran Military Teaching Hospital, Marseille, France, 4Internal medicine and rheumatology, Zobda Quitman Hospital, Fort de France, Martinique, 5virology, Zobda Quitman Hospital, Fort de France, Martinique, 6infectiology, dermatology and internal medicine, CHU de Guadeloupe, Pointe à Pitre, Guadeloupe, 7infectious disease, Zobda Quitman Hospital, Fort de France, Martinique First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: There is no data in the literature about chikungunya fever (chik) and SLE. Martinique (French West Indies) experienced for the first time an outbreak of chik during the year 2014 that was an opportunity to study the relation between SLE and this viral infection.
Methods: The main objective was to describe the evolution of Chik patients with SLE. We also searched to know (1) if chik could modify SLE disease activity, (2) the role of SLE treatments, particularly immunosuppressive drugs, during the Chik episode. We perform a retrospective, monocentric, systematic evaluation of all SLE patients (fulfilling 1997 ACR criteria) followed in the internal medicine and rheumatology unit of the University hospital, between january 2014 and may 2015, assessing (1) SLE activity, (2) the presence of signs compatible with a chik episode. A systematic viral serology was prescribed with their usual biological follow up for all patients. Chik severity was considered if an encephalopathy, myocarditis, hepatitis, or multiorgan failure was present. Results: 167 patients were screened for chik by serology, and we had a result for 110 in may 2015. 56 were included with a positive serology for chik (female: 53; male: 3). Their basic parameters were: mean age at serology (46.5 years, range: 23-81), time since SLE diagnosis to chik episode (12.9 years), renal involvement (42.8%), treatment by immunosuppressant drugs (33.9%), hydroxychloroquine or chloroquine (86.8%), prednisone (64.8%), rituximab (n=3). Clinical signs compatible with a Chik episode were found in 82.6% of the patients with a positive serology. Four patients (7%), all younger than 55 years and one treated by mycophénolate, exhibit severe signs of chik including encephalopathy (n=4) associated with bullous cutaneous lesions (n=3), kidney involvement (n=2). One of these 4 patients who was not immunosuppressed, died in a context of systemic capillary leak syndrome and multiorgan failure. Six of 56 positive patients (10.7%) experienced a lupus flare, all after a symptomatic chik fever: 5/6 were on prednisone, 5/6 hydroxychloroquine and 3/6 (50%) immunosuppressive drugs. Conclusion: SLE can lead to severe Chik infection and should be considered as a group at risk. Chik fever can probably induce SLE flare. Immunosuppressive drugs seem not influence the clinical picture of chik. Disclosure: B. Bigeard, None; K. Polomat, None; E. Javelle, None; S. ARFI, None; L. Brunier-Agot, None; F. MOINET, None; F. Najioullah, None; E. Curlier, None; A. Cabié, None; M. DeBandt, None; G. Jean Baptiste, None; C. Deligny, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/systemic-lupus-erythematosus-and-chikungunya-fever-interactionsduring-the-2014-outbreak-in-martinique
Abstract Number: 1843
Bloodstream Infections in Systemic Lupus Erythematosus Patients Are Associated with Severe Lupus Flares José Jiram Torres Ruiz 1, Ana Barrera-Vargas2, Rigoberto Ortíz-Hernández2, Jorge Alcocer-Varela2 and Diana Gómez-Martín2, 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico, 2Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II Session Type: ACR Poster Session B Session Time: 9:00AM-11:00AM Background/Purpose: Infections are an important cause of mortality and morbidity in systemic lupus erythematosus (SLE) patients. Bloodstream infections (BI), which are especially severe and relatively common in these patients, are associated with a high mortality rate, both during the infectious episode and during follow-up. Whereas there is evidence that bacterial infections can trigger autoimmunity, the relationship between BI and severe lupus flares has not been fully addressed. The aim of this study was to assess whether BI are a risk factor for severe lupus flare. Methods: We performed a retrospective cohort study comparing 107 SLE patients with an episode of BI and 107 hospitalized or ambulatory SLE patients without BI. All subjects satisfied the ACR classification criteria and none of them had severe lupus flare at baseline. Time zero was considered as: a) The episode of BI in the first group b) Hospitalization for another cause, or the medical assessment prior to the last follow-up visit as an ambulatory patient in the non-BI group. Patients were followed for three months. The primary outcome was severe lupus flare according to SELENA-SLEDAI criteria. Differences between groups were assessed by Student’s t test. Cox proportional hazards model was used to estimate the relative risk of severe flare, along with 95% confidence interval. Results: Thirty patients (14%) developed the primary outcome (severe flare) during follow-up; 25 (83.3%) of them had an episode of BI in the previous three months, compared with 5 (16.6%) without a history of BI (p12 (36.6%). Among these flares, severe thrombocytopenia (33.3%) and renal flare (43.3%) were the most frequent. There was no difference in prednisone, cyclophosphamide and mycophenolate mofetil dose between patients who presented severe lupus flare and those who did not. Nevertheless, the basal SLEDAI, C3, C4, anti-dsDNA and azathioprine dose were significantly higher in the former group. After multivariate analysis, the presence of BI (HR 6.24, 95% CI 1.405-27.725, p=0.016), low C4 levels (HR 3.2, 95% CI 1.272-8.078, p=0.014) and lymphopenia = 4 was used to identify SLE patients as well as the family members of the SLE patients. Self-reported RA was further verified by anti-CCP+, anti-RF+, and DMARD usage. Selfreported Sjogrens was confirmed by anti-Ro and/or anti-La. Self-reported hypothyroidism was verified by usage of exogenous thyroid hormones. Selfreported Type I diabetes was further confirmed by usage of Insulin. Proportionality, chi-square, and mixed regression tests were used to analyze prevalence differences of concurrent autoimmune diseases, as well as to detect gender effects among different populations. Results: In EA, SLE patients were more likely to also meet RA criteria [p 98% for all the genotyped SNPs. Serum and sputum samples were collected from 54 SSc-ILD patients at 0, 6, and 12 months. Quantitative CT images were taken at 0,12 months. The possible association of Cav-1 gene SNPs and ILD progression in one-year follow up was determined. Results: A total of 402 SSc patients were recruited to the study (Mean age: 48.9 (12-78) and F:M; 390:20). The clinical characteristics of patients were as follows: Limited cutaneous SSc vs diffuse cutaneous SSc were 60.4% (n=243) vs 39.6 %(n=159), respectively. Interstitial lung disease was observed in 58.6% of patients (n=222). Anti-topoisomerase I antibodies (ATA) were found in 42.6% of patients (n=176). No significant association was observed between any CAV1 SNP and ATA. Genotype analysis and minor allele frequencies of the Cav-1 rs926198, rs959173 and rs 9920 SNP in patients with SSc and controls were shown in table 1. Among SSc-ILD patients who carried the rs959173 C minor allele displayed significantly higher CAV-1 in serum and lesser progression in ILD than in those carrying TT genotype (0.364±0.118 vs 0.247±072, p96%. The percentage of immune cells in total PBMC was analyzed by flow cytometry. Gene expression was analyzed in PBMC and PDC by Q-PCR. PDC were cultured for 24h and IFNa and CXCL4 secretion analyzed by ELISA. Results: First, we observed that the percentage of PDC and CD8+ T cells were significantly decreased in SSc PBMC as compared to HV (0.25%±0.02 vs 0.51% ±0.09; p=0.003 and 13%±0.8 vs 20%±0.9; p 10) were included. Patients with suspected giant cell arteritis were excluded.
Intervention: All patients received tocilizumab infusions (week 0, 4 and 8) without GCs (period 1) and then oral GCs from week 12 to week 24 according to the PMR-AS at week 12 (patients with PMR-AS£10 were treated by 0.15mg/kg whereas those with PMR-AS>10 received 0.30 mg/kg). The primary endpoint was the response to tocilizumab based on PMR-AS£ 10 at week 12. Secondary endpoints were the PMR-AS response at weeks 2,4,8,12,16, 20 and 24 and the GCs sparing effect. Results: At inclusion, median PMR-AS was 36.6 (IQR: 30.4-43.8). At week 12, all patients reached the primary end point and were included in the low dose corticosteroid group. Median PMR-AS at week 12 and 24 were respectively 4.5 (IQR: 3.2-6.8) p< 0.001 and 0.95 (IQR: 0.4-2) p1gm/24hr, and creatinine >1.2 mg/dL. APOs were: fetal death, neonatal death, preterm delivery 100 at 72h of TNF-stimulation and >3-fold induction compared to control), a cluster of 34 genes displayed sustained induction (2 independent experiments) (Figure 1A). 18/34 genes retained high mRNA expression levels despite removal (washing) and blockade (infliximab) of TNFa (Figure 1B-C). In unwashed conditions, active transcription at TNF 72h was variably present depending on the gene. High levels of active transcription were maintained in genes such as IL6, IL8, CXCL1, CXCL2, CXCL3, CXCL6 and TNFAIP3, even after removal of TNF (Figure 1D and not shown). Continuous transcription was NF-kB dependent (Figure 1E). Sustained IL6 promoter chromatin remodeling was retained for days post-wash (Figure 1F and not shown). Highly expressed genes, such as CCL5 and MMP3, displayed minimal ongoing transcription (Figure 1D and not shown). Prolonged (4-8h) inhibition of transcription with ActD at TNF 72h (Figure 2A) significantly decreased TNFAIP3 mRNA (Figure 2B). Expression of other genes, such as IL6, IL8, CXCL1, CXCL3, CXCL6, CCL5 and MMP3, was minimally affected by ActD (Figure 2B and not shown), suggesting increased mRNA stability. Decay rates of mRNA for a group of TNF-inducible genes, such as IL6 and CXCL1, gradually decreased with time (Figure 2C), indicating TNF-inducible mRNA stabilization effect, which was MAPK-dependent (Figure 2D). Decay rates of mRNA of other genes were not dynamically regulated by TNF, and were either persistently stable (e.g CCL5) or unstable (e.g TNFAIP3) (Figure 2C). Conclusion: We have identified a sustained inflammation-related gene expression program in TNF-stimulated RA FLS. Within this program there are different classes of genes based on the relative contribution of transcription and mRNA stability (Figure 2E). TNF drives MAPK-dependent stabilization of certain transcripts and persistent chromatin remodeling in genes such as IL6, indicating TNF-induced memory effect in FLS.
Disclosure: K. Loupasakis, None; C. Sohn, None; L. B. Ivashkiv, None; G. D. Kalliolias, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tnf-confers-pathogenic-memory-in-synovial-fibroblasts-via-chromatinremodeling-nf-kb-dependent-transcription-and-mapk-mediated-mrna-stabilization
Abstract Number: 2013
TIARP Attenuates Autoantibody-Mediated Arthritis Via the Suppression of Neutrophil
Infiltration into the Joint Asuka Inoue 1, Isao Matsumoto1, Yuki Tanaka2, Naoto Umeda1, Hoshimi Kawaguchi1, Hiroshi Ebe1, Yoshihiro Matsumoto3 and Takayuki Sumida1, 1Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 2Department of Internal Medicine, University of Tsukuba, Tsukuba, Japan, 3Product Research Department, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II Session Type: ACR Concurrent Abstract Session Session Time: 2:30PM-4:00PM Background/Purpose: TIARP (TNFα-induced adipose-related protein) is dominantly expressed in macrophages (Mφ), neutrophils (PMN) and fibroblast-like synoviocytes (FLS). Recently, we found that TIARP functions as a negative regulator in autoimmune arthritis through the suppression of IL-6 production, NF-κB, STAT3 signaling in Mφ, although the molecular mechanism of TIARP-expressing cells in arthritis remains uncertain. The purpose of this study is to elucidate the functional role of TIARP in the pathogenesis of arthritis, especially focusing on PMN and FLS. Methods: (1) K/BxN serum-transferred arthritis was induced to TIARP-/-or WT, then the ankle thickness was monitored. Mice were also treated with intravenous administration of anti-Gr1 Ab (for the depletion of PMN) or control Ab every other day after the induction of arthritis. (2) RNAs were extracted from TIARP-/-or WT PMN, subsequently compared by Gene chip. (3) The expression of CXCR1 and CXCR2 on PMN was analyzed, and the chemoattractant activity of TIARP-/- or WT PMN was tested by trans-well chemotaxis assays. (4) Using TIARP-/-or WT FLS, the expression of IL-6, TNFα and CXCL2 after TNFα stimulation were compared. (5) To verify the effect of CXCL2, we performed the chemotaxis assay of PMN by applying to the lower chamber with anti-CXCL2 Ab. (6) The production of IL-17, TNFa and IL-6 from PMN stimulated by immune-complex (IC) were measured by ELISA. (7) Anti-IL-6R Ab was administrated every other day after the induction of serum transferred arthritis. Results: (1) The severity of arthritis in TIARP-/- mice was markedly exacerbated, and the recruitment of PMN into the joint was significantly enhanced. TIARP/-mice treated with anti-Gr1 Ab showed significantly reduced cellular infiltrate into the joint, and reduced synovial thickening. (2) Gene ontology analysis of up-regulated genes in TIARP-/-PMN demonstrated the enrichment of genes involved in chemotaxis. (3) The expression of CXCR1/2 was significantly higher in TIARP-/- PMN, and the recruitment capacity was enhanced. (4) The expressions of IL-6 and CXCL2 in TIARP-/- FLS were significantly higher than in WT, whereas RANKL, MMP3 and MMP9 were not different. (5) The numbers of migrated PMN were significantly decreased by the addition of antiCXCL2 Ab. (6) The production of IL-17, TNFa and IL-6 were comparable between WT and TIARP-/-PMN. (7) Serum-transferred arthritis in TIARP-/- mice was attenuated by the blockade of IL-6R signaling, and recruitment of PMN into the joint of TIARP-/-mice was suppressed. Conclusion: TIARP might down-regulate the production of CXCL2 from FLS and the expression of CXCR1/2 in PMN, resulting in the protective ability of neutrophil migration in arthritic joints, probably via the inhibition of IL-6 signaling. Disclosure: A. Inoue, None; I. Matsumoto, None; Y. Tanaka, None; N. Umeda, None; H. Kawaguchi, None; H. Ebe, None; Y. Matsumoto, None; T. Sumida, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/tiarp-attenuates-autoantibody-mediated-arthritis-via-the-suppression-ofneutrophil-infiltration-into-the-joint
Abstract Number: 2014
Deficiency of IL-27 Exacerbate Sjögren’s Syndrome through Inhibiting Differentiation of Type 1 Regulatory T Cells Genhong Yao1, Bingyu Shi1, Jingjing Qi1, Ying Wang1, Weiwei Chen1, Xiaojun Tang1, Dandan Wang2, Xuebing Feng1 and Lingyun Sun1, 1Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, 2Department of Rheumatology and immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II Session Type: ACR Concurrent Abstract Session Session Time: 2:30PM-4:00PM Background/Purpose: Sjögren's Syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation involving the exocrine glands, particularly the salivary and lacrimal glands. The pathogenesis of SS is complicated with many respects remaining elusive. IL-27, a member of IL-12 cytokine family, has the pro- and anti-inflammatory properties during immune responses. IL-27 can induce the differentiation of type 1 regulatory T (Tr1) cells from human naive CD4+ T cells. Recent studies have shown that IL-27 was involved in anti-inflammatory functions in SS. However, the underlying mechanism of IL-27 in SS is still unknown. In the present study, Tr1 cells were studied in IL-27 knock-out and wild-type SS models and patients for the purpose to explore the specific mechanism of IL-27 in SS. Methods: IL-27 mRNA expression in PBMC of SS patients was detected by real-time PCR. Serum IL-10 of SS patients and model animals was determined by ELISA. Infiltrated IL-10+ cells in labial gland of SS patients were assessed by immunohistochemistry. Tr1 cells in human peripheral blood and mice spleen were measured by flow cytometry. Results: IL-27 mRNA expression was decreased in SS patients. The level of IL-27 mRNA in patients with glandular infiltration was higher than those with extraglandular manifestation (Fig 1).
Figure 1 In SS patients, infiltrated IL-10+ cells in labial gland were significantly decreased (Fig 2 A and B). Serum IL-10 was significantly decreased in SS patients than healthy controls (Fig 2C). Compared with control, the frequency of Tr1 cells in peripheral blood of SS patients significantly reduced (Fig 2D).
Figure 2 IL-27 deficient NOD (Non-Obese Diabetic) mice displayed more severe SS-like autoimmune disorders than NOD mice. The saliva flow rate was decreased and the submandibular gland weight/body weight index increased (Fig 3A and B). The percentage of CD4+IL-10+ Tr1 cells in splenocytes was significantly lower than NOD mice (Fig 3C). The serum IL-10 also decreased significantly (Fig 3D).
Figure 3 Conclusion: In general, these findings indicated that IL-27 deficiency deteriorated the disease symptoms of SS through loss of inducing Tr1 cells differentiation. Our data suggested that IL-27 and IL-27-induced Tr1 cells played an important role in the pathogenesis of SS.
Disclosure: G. Yao, None; B. Shi, None; J. Qi, None; Y. Wang, None; W. Chen, None; X. Tang, None; D. Wang, None; X. Feng, None; L. Sun, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/deficiency-of-il-27-exacerbate-sjogrenssyndrome-through-inhibiting-differentiation-of-type-1-regulatory-t-cells
Abstract Number: 2015
Targeting Non-Canonical NF-Kappa B Signaling Inhibits Angiogenesis in a Novel 3D Model of Rheumatoid Arthritis Synovial Angiogenesis Chrissta X. Maracle 1, Paulina Kucharzewska2, Boy Helder1, Arjan W. Griffioen3, Henric K. Olsson2 and Sander W. Tas4, 1Clinical Immunology and Rheumatology, Amsterdam Rheumatology and immunology Center | Academic Medical Center, Amsterdam, Netherlands, 2Astra Zeneca, Mölndal, Sweden, 3Medical Oncology, VU University Medical Center, Amsterdam, Netherlands, 4Clinical Immunology and Rheumatology, Amsterdam Rheumatology and immunology Center | Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II Session Type: ACR Concurrent Abstract Session Session Time: 2:30PM-4:00PM Background/Purpose: Pathological angiogenesis is a crucial part of disease progression in rheumatoid arthritis (RA) and is often considered the switch from acute to chronic inflammation. It is a complex process mediated by several different cell types in the inflamed synovium. However, many of the in vitromodels of angiogenesis focus solely on endothelial cells (EC), even though RA fibroblast-like synoviocytes (FLS) and immune cells also contribute to angiogenesis. Hence, a system that includes RA FLS as well as RA synovial fluid (SF) containing immune cell products such as cytokines, chemokines and growth factors, would be more representative of synovial angiogenesis. We have recently demonstrated that the non-canonical NF-kB pathway, with its main regulatory enzyme NF-kB inducing kinase (NIK), plays an important role in synovial angiogenesis. Therefore, we set out to investigate whether inhibition of this pathway may hold therapeutic potential in mitigating pathological angiogenesis associated with RA. Objective: Generate a representative 3D in vitromodel of RA synovial angiogenesis and screen the effects of targeting the non-canonical NFκB pathway using siRNA or small molecule pharmacological inhibitors. Methods: Human primary EC were co-cultured with RA FLS after pre-incubation with cell tracker dyes and incubated overnight to form spheroids. Subsequently, spheroids were plated in collagen gel and stimulated with 10% RA SF, growth factors (GF) or wellknown activators of non-canonical NF-kB signaling (lymphotoxin beta (LT) or LIGHT). To establish NIK dependency, EC were pre-transfected with NIK-targeting siRNA before incorporation into spheroids. Furthermore, several pharmacological inhibitors were screened for their ability to block sprout formation. Spheroids were imaged by confocal microscopy and quantified using Leica QWin Plus software. Results: We established a robust 3D model of angiogenesis containing both EC and RA FLS. LT, LIGHT, RA SF and GF stimulations led to significant increases in sprout formation as compared to basal conditions (p +2.0) of cardiac and aortic dimensions, as well as qualitative descriptions of abnormal ventricular function, chamber enlargement, and valvular dysfunction (at least moderate stenosis or regurgitation). Bivariate analyses of outcomes were performed with potential risk factors for morbidity including demographics, maternal medications during pregnancy, fetal heart rate at time of detection and lowest documented fetal rate, fetal echo dilated cardiomyopathy (DCM), endocardial fibroelastosis or hydrops, postnatal septal defects, permanent pacemaker (PPM) placement, age at PPM implantation and number of years with PPM. Results: Echo reports were available for 15 (8.4%) children age 0-1, 40 (22.5%) >1-5, 34 (19.1%) >5-10, 26 (14.6%) >10-15, 33 (18.5%) >15-20, and 30 (16.9%) >20. Left ventricular (LV) systolic function was qualitatively abnormal in 13.7% and lownormal in 9.1%. Abnormal LV function was more frequent in age groups 0-1 (26.7%) and >20 (26.7%) compared to others (p=0.004). In all ages, decreased LV function associated with lower fetal heart rate at detection of CHB (p=0.012) and nadir rate (p=0.002), as well as fetal DCM (p=0.035) and hydrops (p=0.048). Abnormal LV function also associated with need for PPM (p=0.029), younger age at PPM implantation (p=0.042), longer period of pacing (p=0.014), atrial septal defect (p=0.012) and black race (p=0.019). LV end diastolic dimension was enlarged in 21.5% by z score and 20.6% qualitatively. LV dilation associated with fetal DCM (p=0.04) and black race (p=0.028). The aortic root and/or ascending aorta were dilated in 27.8%, associated with a younger age (p=0.001) and lower fetal ventricular rate at detection (p=0.04). Valvular disease was present in 8.7%, associated with older age (p=0.001), fetal DCM (p=0.033), PPM (p=0.042) and longer period of pacing (p80% of cases. Results: We found 69 lymphomas during 75,661 person-years (py) in the bDMARD treated patients, 241 lymphomas (237,789 py) in the bio-naïve patients, and 1413 lymphomas (2,890,131 py) in the general population referent cohort. All of the bDMARD treated lymphoma patients were exposed to TNFi, 3 also to abatacept, 2 to anakinra and 2 to rituximab. Compared to the general population both bDMARD treated (HR=2.5; 95% CI 2.0-3.3) and bio-naïve patients (HR=2.2; 95% CI 1.9-2.5) were at increased risk for lymphoma. The lymphoma risk following start of a first TNFi (mean follow-up 5.9 years, maximum follow-up 15 years) or start of a first bDMARD were similar and not significantly increased compared to bio-naïve RA patients (HR bDMARD=1.2; 95% CI 0.9-1.6). There were no significant differences in HRs with age and calendar period at bDMARD start, time since treatment start or time on active bDMARD treatment in bDMARD treated vs. bio-naive RA. We noted a higher point estimate of lymphoma risk in men (HR=1.5) vs. women (HR=1.1); this difference was borderline significant (p=0.04). There were no clear differences in lymphoma risks for different TNFi drugs (infliximab, etanercept, adalimumab). Due to few events, we abstained from assessing lymphoma risks for specific other bDMARDs. Compared to the general population, bio-naive and bDMARD-treated RA patients were both at increased risks for most common lymphoma subtypes (Table). Conclusion: Overall, the lymphoma risk in RA remains increased compared to the general population. TNFi-treatment with a mean follow-up for 5.9 years or overall bDMARD therapy does not substantially influence this risk. The distribution of lymphoma subtypes warrants further assessment. Table Hazard Ratios for lymphoma overall and for specific lymphoma subtypes in patients with RA, treated with bDMARD (n=13,240) 1998-2012 and bio-naïve RA patients (n=46,568) versus general population comparator subjects (n=458,846) 20012012. Lymphoma N. lymphoma in HR (95% N. lymphoma in HR (95% 6 subtype¹ CI) CI)6 bDMARD treated bio-naive RA vs. RA vs. general population general population All lymphoma 69/1413 2.5 (2.0-3.3) 241/1413 2.2 (1.9-2.5) B-cell lymphoma 24/515 2.7 (1.7-4.1) 100/515 2.5 (2.0-3.1) 2 18/371 2.9 (1.8-4.7) 80/371 2.8 (2.2-3.6) DLBCL Follicular 9/203 2.1 (1.1-4.1) 29/203 1.8 (1.2-2.6) lymphoma 9/309 1.7 (0.9-3.3) 22/309 0.9 (0.6-1.4) CLL3 7/69 6.0 (2.79/69 1.4 (0.7-3.0) T/NK4 cell 13.3) lymphoma Hodgkin lymphoma 7/55 4.7 (2.013/55 2.7 (1.4-5.1) 11.0)
Disclosure: K. Hellgren, None; C. Sundström, None; J. Askling, AstraZeneca, Pfizer, UCB, Roche, Merck, BMS, Abbvie, 9; E. Baecklund, None. View Abstract and Citation Information Online -
¹According to World Health Organization (WHO) classification, 2DLBCL= Diffuse large B-cell lymphoma, 3CLL= Chronic lymphocytic lymphoma 4 T/NK= T and natural killer cell, 6 Hazard ratios (HRs) with 95 % confidence interval adjusted for age, sex, and calendar time. http://acrabstracts.org/abstract/lymphoma-in-patients-with-rheumatoid-arthritis-treated-with-biologic-drugs-long-term-follow-up-
Abstract Number: 2053
Adjustment of Skeletal Muscle Mass Estimates for the Extent of Adiposity Strengthens Relationships with Functional Outcomes in Rheumatoid Arthritis Joshua Baker1, Jon Giles2, Mary Leonard3, David Weber4, Jin Long5, Erik Jorgenson6 and Patricia P. Katz7, 1Medicine/Rheumatology, University of Pennsylvania, Philadelphia, PA, 2Rheumatology, Columbia University Medical Center, NY, NY, 3Stanford University, Palo Alto, CA, 4Rochester University, Rochester, NY, 5Children's Hospital of Philadelphia, Philadelphia, PA, 6University of Pennsylvania, Philadelphia, PA, 7Rheumatology, UCSF, SF, CA First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects II: Infection, Malignancy and Other Comorbidites in RA Session Type: ACR Concurrent Abstract Session Session Time: 2:30PM-4:00PM Background/Purpose: Skeletal muscle loss in rheumatoid arthritis (RA) has been described in association with poor physical functioning. Greater adiposity is simultaneously associated with both greater muscle mass and worse physical function and therefore is a potential confounder in the assessment of relationships between muscle and physical function. We aimed to determine if adjustment of muscle mass estimates for adiposity improves correlations with physical function in patients with RA.
Methods: Three large independent RA cohorts from academic institutions in the US were retrospectively analyzed in a crosssectional design. Whole-body Dual-Energy Absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2) were converted to age, sex, and race-specific Z-Scores using NHANES reference ranges. Fatadjusted ALMI Z-Scores (ie. standard deviations below average for that level of adiposity) were determined using a novel, comprehensive residual method to adjust for the normal age, sex, and race-specific associations between ALMI and FMI Z-Scores within NHANES. Associations between ALMI Z-Scores (standard and fat-adjusted) and physical functioning were assessed over the range of adiposity adjusting for age, sex, study, and disease activity measures, and assessing for interaction. Functional outcomes assessed included the Health Assessment Questionnaire (HAQ), Valued Life Activities assessment (VLA), and Short Physical Performance Battery (SPPB). Low lean for age was defined as an ALMI or fat-adjusted ALMI Z-Score of ≤ -1.
Results: A total of 415 patients were studied across the cohorts. The combined cohort had a mean ALMI Z-Score of -0.54, mean FMI Z-Score of -0.21, and mean fat-adjusted ALMI Z-Score of -0.53 (all p170 days). In the C3 cluster, ABA-treated pts were slower to flare than pbo pts (mean 194 vs 96 days) and had the largest decrease in total BILAG
score and greatest difference from pbo (Figure). Conclusion: In a re-analysis of the Phase IIb abatacept trial in SLE, whole blood de-convolution identified 4 distinct peripheral blood mononuclear cell phenotypic clusters at baseline. These clusters demarcated distinct clinical characteristics and response to therapy. Whole blood de-convolution might provide insights into specific immune cell-driven disease pathogenesis and might improve patient stratification and enrich interpretation of trial data. 1. Abbas AR, et al. Genes Immun 2005;6:319–31. 2. Abbas AR, et al. PLoS One 2009;4:e6098. 3. Merrill JT, et al. Arthritis Rheum 2010;62:3077–87. Disclosure: S. Bandyopadhyay, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; S. Connolly, Bristol-Myers Squibb, 1,BristolMyers Squibb, 3; O. Jabado, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; S. Kelly, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; M. Maldonado, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Westhovens, Roche Pharmaceuticals, 2,BristolMyers Squibb, 8,Janssen, Galapagos, 5; P. Nash, Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 2,Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 5,Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 8; J. Merrill, Bristol-Myers Squibb, GlaxoSmithKline, Xencor Macrogenics, 2,Bristol-Myers Squibb, GlaxoSmithKline, Mallinckrodt, MedImmune, Lilly, UCB, Takeda, Abbvie, Anthera, Neovacs, Receptos, Celgene, 5; R. Townsend, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/de-convolution-of-whole-bloodtranscriptomic-data-from-a-phase-iib-randomized-double-blind-placebo-controlled-trial-of-abatacept-in-systemic-lupuserythematosus
Abstract Number: 2068
Low Complement Is Associated with SLE Classification Criteria and Organ Damage Laura Durcan1, Wei Fu2 and Michelle Petri1, 1Rheumatology, Johns Hopkins University Hospital, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment III: Biomarkers Session Type: ACR Concurrent Abstract Session Session Time: 2:30PM-4:00PM Background/Purpose: Low complements are included in the SLICC classification criteria for systemic lupus erythematosus (SLE) but are not considered in the ACR classification. As a result, the importance of low complement and its relationship to cumulative organ damage has not been systematically investigated. We evaluated the relationship between low complement, C3 and C4, SLICC criteria and organ damage in SLE. Methods: As part of a longitudinal lupus cohort, damage accrual and organ manifestations were evaluated quarterly. Damage was measured using SLICC/ACR Damage Index (SDI). C3 and C4 were measured as part of standard clinical care. Those with and without a history of low complement were compared and an odds ratio calculated and adjusted for ethnicity. Results: 2399 patients were included in this analysis. 53% were Caucasian and 38% African American, the remainder had other ethnicity, mostly Asian. Low C4 was demonstrated in 47% and low C3 in 55%. The relationship between low complement and the SLICC Classification Criteria is outlined in Table 1. Low complement was more common in those with serositis, renal involvement, hematologic and neurologic criteria. Addressing the SDI, both low C3 and low C4 associated significantly with stroke, pulmonary hypertension, valvular heart disease and all renal damage parameters. Avascular necrosis, hypertension and osteoporosis were also more common in those who had low complement. Significant relationships were demonstrated between low C4 in particular and seizures, scarring of the panniculum and mesenteric insufficiency while diminished C3 associated with pleural fibrosis and cardiomyopathy. These odds ratios remained significant when adjusted for ethnicity. Conclusion: Low complement associated strongly with the components of the SLICC criteria. There was also more damage accrual in those with low complement. This was particularly true in terms of renal outcome but also when considering those components of the damage index which associate with prednisone exposure. This points towards a more severe spectrum of disease in those with low complement and highlights the importance of these serological markers in the diagnosis and prediction of long-term outcomes in SLE. The relationship between low complement, stroke, valvular disease and pulmonary hypertension has not previously been described, but is fascinating given the concern for complement activation as part of antiphospholipid syndrome. Table 1. The relationship between low C3 and C4 and the SLICC Classification Criteria.
Low C3 OR (CI) Malar rash 1.22 (1.041.43) Discoid rash 1.36 (18.104.22.168) Photosensitivity 0.8 (0.680.94) Oral/Nasal Ulcers 0.74 (0.630.87) Arthritis 1.05 (0.881.25) Serositis Pleurisy 1.47 (1.251.73) Pericarditis 1.78 (1.462.18) Renal disorder 3.77 (3.144.48) Neurologic Seizures 1.51 (1.142.00) Acute confusional 2.39 (1.52state 3.77) Hematologic Hemolytic anemia 3.63 (2.615.04) Leukopenia 2.45 (2.082.89) Lymphopenia 2.13 (1.802.86) Thrombocytopenia 2.31 (1.872.86) Immunologic Anti-dsDNA 4.97 (4.16,5.94) Anti Sm 3.65 (2.89,4.61) AntiAnti-cardiolipin 1.76 (1.49phospholipid 2.08) Anti- B2 Gly 1.97 (1.562.50) False positive 2.24 RPR (1.72,2.93) LAC 1.49 (1.231.79) ANA 2.1 (1.34,3.3)
Low C4 OR (CI) 1.24 (1.061.46) 1.12 (0.921.38) 0.92 (0.781.08) 0.86 (0.731.01) 1.31 (1.11.57) 1.44 (1.231.7) 1.69 (1.392.05) 3.22 (2.723.81) 1.54 (1.172.02) 1.98 (1.313.01) 2.99 (2.234.01) 2.09 (1.772.46) 2.13 (1.812.52) 2.08 (1.702.55) 5.28 (4.39,6.35) 2.96 (2.39,3.66) 1.84 (1.562.17) 1.81 (1.442.27) 2.97 (2.29,3.87) 1.49 (1.241.79) 2.97 (1.78,4.94)
Table 2. SLE Damage index and relationship to low C3 and low C4.
SDI DAMAGE COMPONENT Cataract Retinal changes Cognitive impairment Seizure CVA Cranial or Peripheral neuropathy Transverse myelitis GFR 80% was determined for each drug and the drugs in combination over the12 months. Propensity score matched weights were used to balance covariates when comparing risk ratios for each outcome among triple and combination therapy. Results: A total of 3,204 TNFi-MTX and 1,160 triple therapy patients met the eligibility criteria (mean [SD] age at index 61  vs. 62 , 16.0% vs. 9.0% female). After 12 months, persistence in the TNFi-MTX arm was significantly greater by all three approaches in both crude and propensity score weighted models (table1); favoring TNFi combination treatment. Twelve-month adherence to TNFi-MTX was approximately 41% higher than adherence to triple therapy [24% vs. 17%, RR: 1.41 (95%CI: 1.20,1.66)].
Conclusion: US Veterans initiating TNFi-MTX therapy consistently showed significantly greater persistence and adherence than those receiving triple therapy in clinical practice. Given differences between treatment strategies in terms of cost, tolerability, and patient preference, additional research focused on identifying factors that account for the observed differences in persistence and adherence will be important in informing RA management.
Disclosure: B. Sauer, Amgen, 2; C. C. Teng, Amgen, 2; J. Leng, Amgen, 2; T. R. Mikuls, Roche /Genetech, 2,Pfizer Inc, 5; J. R. Curtis, Roche, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo,AbbVie, 2,Roche, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo,AbbVie, 5; B. S. Stolshek, Amgen Inc., 3,Amgen Inc., 1; D. Tang, Amgen Inc., 3,Amgen Inc., 1; G. W. Cannon, Amgen, 2. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/higher-persistence-and-adherence-withcombination-therapy-with-tumor-necrosis-factor-inhibitormethotrexate-combination-versus-triple-therapy-in-us-veterans-withrheumatoid-arthritis
Abstract Number: 2103
Temporal Trends in Drug Prescription, Utilization and Costs Among Rheumatoid Arthritis (RA) Patients Show Wide Regional Variation Despite Universal Drug Coverage Mark Tatangelo1, Michael Paterson2, George A. Tomlinson3, Nick Bansback4, Jessica Widdifield5, Tara Gomes2 and Claire Bombardier6, 1University of Toronto, Toronto, ON, Canada, 2Institute of Clinical Evaluative Sciences, Toronto, ON, Canada, 3Medicine, Mount Sinai Hospital, Toronto, ON, Canada, 4Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada, 5University Health Network, Toronto, ON, Canada, 618 Strathearn Blvd, University of Toronto, Toronto, ON, Canada First publication: September 29, 2015 SESSION INFORMATION
Session Date: Monday, November 9, 2015 Session Title: Health Services Research II: Rheumatoid Arthritis Treatment and Healthcare Utilization Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Monitoring of drug use and costs can: describe trends in expenditures over time, identify regional variations in access and indicate physicians' uptake of best-practice guidelines. Our aim was to describe drug use and costs of biologic (bDMARD) and conventional synthetic Disease Modifying Anti-Rheumatic drug (csDMARDs) in the context of singlepayer universal drug coverage. Methods: We performed a population-based analysis, identifying all RA patients (from 1995 to 2013) who were aged 65 years and older using a validated algorithm (1) (n=37,012). All patients received identical public drug coverage from a single public payer. Prescriptions were determined using the pharmacy claims database of the Ontario Drug Benefit Program. For each patient we recorded the annual number of prescriptions and costs for csDMARDs and bDMARDs and region of residence. Trends in annual drug use and costs were graphed by drug class and regional health authority. Results: The total number of patients receiving RA medications tripled from 14,222 in 1995 to 37,012 in 2013. During that same time period csDMARD use and costs increased from $2.1M in 1995 to $8.5M in 2013(Fig 1.). When bDMARDs were introduced in 2001, 105 patients received bDMARDs (0.4%) increasing to 3226 patients (11%) in 2013. During that period the costs of bDMARDS increased from $0.78M to $54.6M (Fig 1.). In 1995, per-patient drug costs in each regional health authority were an average of $500 per patient per year(Fig 2.). Since the introduction of bDMARDs in 2001, total cost and per-patient cost variation among regions has increased considerably, with drug expenditure in 2013 ranging from $1200 per patient per year to $2500 per patient per year(Fig 2.). Conclusion: The number of patients with RA increased linearly over time from 1995 to 2013. The proportion of patients receiving csDMARDs grew at the same rate as the population of patients with RA. The introduction of bDMARDs was associated with an exponential rise of bDMARD use and cost over time driving the increase in total drug costs however the use of bDMARDs was lower than in the US where 27% of patients with a mean age of 70 received bDMARDs (2). When analyzed by region, adoption of bDMARDs was associated with differential and widening variation in regional drug costs over time, indicating unequal use of bDMARD not explained by differences in reimbursement criteria. We hypothesize that regional access to rheumatology care and rheumatologist's varying propensity to prescribe bDMARDs are the primary drivers of inequitable utilization of bDMARDs. References 1.
Widdifield et al. , Arthritis Care Res, 2013.
Zhang et al., Arthritis Care Res, 2013.x
Disclosure: M. Tatangelo, None; M. Paterson, None; G. A. Tomlinson, None; N. Bansback, None; J. Widdifield, None; T. Gomes, None; C. Bombardier, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/temporal-trends-in-drug-prescriptionutilization-and-costs-among-rheumatoid-arthritis-ra-patients-show-wide-regional-variation-despite-universal-drug-coverage
Abstract Number: 2104
Influence on Treatment Decision Making of Providing Numerical Ranges of SideEffect Risks Nick Bansback1,2, Mark Harrison3, William G Dixon4 and Paul Han5, 1Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada, 2School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada, 3Centre for Health Evaluation and Outcomes Sciences, St Paul's Hospital, Vancouver, BC, Canada, 4Manchester Academic Health Sciences Centre, Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, United Kingdom, 5Center for Outcomes Research and Evaluation, Maine Medical Center, Portland, ME First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Health Services Research II: Rheumatoid Arthritis Treatment and Healthcare Utilization Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Doctors and patients make treatment decisions after weighing benefits and harms. For harms, while people prefer treatments with smaller risks, how they react to ambiguity—i.e., uncertainty arising from limitations in the reliability, credibility, or adequacy of risk information (often presented as a range of risks) – is less well understood. The objective of this study was to determine the relative importance of the magnitude of risk and ambiguity in the treatment decision-making context. Methods: We invited members of an online panel to complete a survey which sought choices between two hypothetical rheumatoid arthritis treatments based on different levels of 4 attributes: probability of benefit (40%,55%,70%), probability (risk) of iatrogenic harm requiring treatment withdrawal (10%,20%,30%), ambiguity regarding risk of harm, expressed by risk estimate imprecision (none: point-estimate, low: range+/-5%, high: range+/-10%), and life expectancy (8,9,10 years). Each respondent
answered 10 pairwise Discrete Choice Experiment questions indicating strength of preference for each treatment, described using differing levels for each attribute as generated by a D-efficient experimental design. Conditional and mixed logit models were used to estimate coefficients for each attribute level and allow for estimation of marginal willingness to pay (WTP), in this case the duration of life they would be willing to give up to move between each of the attribute levels in the survey. Results: Of 252 respondents, the mean age was 34 (range 20-67), 68% were male, and 52% had an education level of high school or less. Respondents placed greatest value on greater probability of benefit (WTP=1.34 years for 70% vs 40%, p180 days (p180 days (p75% during follow-up. Most of the new damage accrued during follow-up is treatment-associated; however, significant disease-associated damage, especially from peripheral arterial manifestations also occurs. These results emphasize the cumulative burden of disease associated with GCA even after initial diagnosis and treatment. Damage at baseline and last follow-up in patients with giant cell arteritis Organ System VDI LVVID N=204 N=204 Baseline Follow- Baseline Followup up N* (%) N* (%) N* (%) N* (%) Cardiac 21 (10) 44 (22) 33 (16) 51 (25) Peripheral vascular** 58 (29) 66 (32) 53 (26) 66 (32) Musculoskeletal 25 (12) 51 (25) 25 (12) 51 (25) Ocular 45 (22) 89 (44) 54 (26) 92 (45) Ear, Nose, and Throat 1 (0.5) 1 (0.5) 1 (0.5) 1 (0.5) Gastrointestinal 1 (0.5) 2 (1) 0 (0) 1 (0.5) Neuropsychiatric 4 (2) 8 (4) 5 (3) 6 (3) Endocrine 8 (4) 10 (5) 11 (5) 9 (4) Hematology/Oncology 0 (0) 8 (4) 0 (0) 7 (3) Skin 1 (0.5) 1 (0.5) 4 (2) 7 (3) Pulmonary 4 (2) 5 (3) N/A N/A Renal 0 (0) 0 (0) N/A N/A Other 7 (3) 15 (7) 27 (13) 44 (22) VDI = Vasculitis Damage Index; LVVID = Large-Vessel Vasculitis Index of Damage N* = number with ≥1 item captured in that category ** Peripheral vascular manifestations NA = not applicable due to no items in this organ system appearing in LVVID Disclosure: T. A. Kermani, None; A. G. Sreih, None; D. Cuthbertson, None; S. Carette, None; G. S. Hoffman, None; N. A. Khalidi, None; C. L. Koening, None; C. A. Langford, None; C. A. McAlear, None; P. A. Monach, None; L. W. Moreland, None; C. Pagnoux, None; P. Seo, None; K. J. Warrington, None; S. R. Ytterberg, None; P. A. Merkel, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/damage-assessment-in-giant-cell-arteritis
Abstract Number: 2157
Relapse Characteristics and Glucocorticoid Use in Patients with Biopsy-Proven Giant Cell Arteritis Matthew J. Koster1, Cristian Labarca2, Cynthia S. Crowson3, Ashima Makol1, Steven R. Ytterberg4, Eric L. Matteson1 and Kenneth J. Warrington1, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Rheumatology, Clinica Alemana Universidad del Desarrollo, Santiago, Chile, 3Health Sciences Research, Mayo Clinic, Rochester, MN, 4Rheumatology Division, Mayo Clinic, Rochester, MN First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Vasculitis II Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Relapses in patients with giant cell arteritis (GCA) are common and often lead to higher cumulative use of glucocorticoids. This study aims to evaluate the relapse characteristics and glucocorticoid use among a large single-institution cohort of patients with biopsy-proven GCA. Methods: A retrospective review was performed to identify all patients with biopsy-proven GCA from January 1998 to December 2013. Demographic, clinical, laboratory and treatment data at baseline and subsequent follow visits were collected. Relapse was defined as recurrence of clinical manifestations compatible with spectrum of GCA and/or increase in inflammatory markers (ESR/CRP), not otherwise explainable, which required reintroduction or increased dose of glucocorticoid therapy. Comparisons between relapse groups were performed using Chi-square and Kruskal-Wallis tests. Time to daily dose of 40 mg and ≤40 mg were compared using Cox models. Results: The cohort included 286 patients with biopsy-proven GCA (213 females and 73 males, mean [±SD] age 75.0 [±7.6] years) with a mean (±SD) followup of 6.0 (±3.9) years. During followup 213 patients (75%) had one or more relapses. In patients experiencing a relapse, 50% of relapses occurred during the first year, 68% during the first two years and 79% during the first five years of follow up. The median relapse rate observed was 0.4 [Interquartile range (IQR) 0.21, 0.64] relapses per year. We further evaluated patients in three groups; no relapse, low relapse rate (40mg/day with patients receiving ≤40mg/day, the mean (±SD) prednisone dose was higher at the following intervals: one year [7.4 (±2.3) g vs. 5.8 (±2.1) g; p40 mg/day reached 40mg/day led to earlier steroid discontinuation without increase in glucocorticoid-associated adverse events. Disclosure: M. J. Koster, None; C. Labarca, None; C. S. Crowson, None; A. Makol, None; S. R. Ytterberg, None; E. L. Matteson, Novartis/Sanofi/Centocor-Jansen/Celgene/Amgen/Roche/Genentech/Mesoblast/Pfizer, 2; K. J. Warrington, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/relapse-characteristics-and-glucocorticoiduse-in-patients-with-biopsy-proven-giant-cell-arteritis
Abstract Number: 2158
Mortality Associated with Giant Cell Arteritis from 1980 to 2011: An Analysis of the French National Death Certificate Database Achille Aouba1, Solange Gonzalez-Chiappe2, Mireille Eb3, Claire Delmas1, Grégoire Rey3, Alfred Mahr2 and Boris Bienvenu1, 1Internal Medicine, Hospital Caen, Caen, France, 2Internal Medicine, Hospital Saint-Louis, Paris, France, 3Inserm-CépiDc, Hospital Bicêtre, Le Kremlin-Bicêtre, France First publication: September 29, 2015 SESSION INFORMATION Session Date: Monday, November 9, 2015 Session Title: Vasculitis II Session Type: ACR Concurrent Abstract Session Session Time: 4:30PM-6:00PM Background/Purpose: Data from mostly small cohorts consistently suggest that a diagnosis of giant cell arteritis (GCA) does not substantially affect survival but GCA- and GCA treatment-related morbidity may result in specific patterns of causes of death. Large databases of death certificates allow for studying patterns of mortality associated with specific medical conditions and determining changes over time in the extent to which they contribute to mortality. Methods: We obtained data from multiple-cause mortality files compiled by the French Epidemiological Center for the Medical Causes of Death (CépiDC) for 1980–2011. GCA cases were defined as decedents ≥55 years old with International Classification of Diseases (ICD) codes 446.5 (ICD-9) or M31.6 (ICD-10) listed as the underlying or contributory cause of death. We calculated annual death rates (using national census data as a denominator) and average ages at death for GCA and for the general French population; time trends were analyzed by linear regression. To investigate the relation between deaths associated with GCA due to other medical disorders, we calculated standardized mortality odds ratios (SMORs) for 16 conditions frequently listed as causes of death in the general population or with a known association with GCA morbidity or mortality. SMORs were computed from more detailed data from the death certificates from 2000 to 2011, in which GCA was listed as a contributory cause of death. Results: Among the 14,927,440 death records compiled over the 32-year period for decedents ≥55 years old, 15,020 listed a diagnosis of GCA. Females accounted for 68% of GCA cases and 51% of general-population death records. GCA death rates increased from 1980 to 2000 (P200 mg/dl. aGAPSS was calculated for each patient by adding points corresponding to the risk factors previously reported by Bertolaccini (3 points for hyperlipidemia, 1 point for hypertension, 5 points for aCL IgG/IgM, 4 points for anti-B2GPI IgG/IgM, 4 points for LA). Pearson Chi-squared or Fisher’s exact test univariate analysis with two tailed P value was used to evaluate correlation between aGAPSS and clinical manifestations. Results: Patients with APS showed a baseline aGAPSS of 8.5+/-3.3 (Mean +/- SD, range 4-16). Primary and secondary APS patients showed aGAPSS of 8.0+/- 3.4 (range 4 -14) and 8.7 +/- 3.3 (range 4-16) respectively. There is no statistical difference in aGAPSS between primary and secondary patients, p=0.3021. No difference in aGAPSS was observed between male 8.6 +/- 3.2, (range 4-14) and female 8.5+/-3.4, (range 4-16) APS patients, p=0.86. Higher aGAPSS values were seen in patients who experienced thrombosis 9.4 +/- 3.2, (range 4-16) compared to those with pregnancy morbidity 6.7 +/- 2.8, (range 4 -14), p=0.0001. Patients who experienced both thrombosis and pregnancy morbidity showed higher mean aGAPSS when compared to those with pregnancy morbidity alone, but it was not statistically different, p= 0.087. There is no difference in aGAPSS score among patients who experienced thrombotic recurrence [8.7+/- 3.6, (range 4-14)] compared to those without recurrence [9.7 +/3.0, (range 4 – 16)], p= 0.19. Conclusion: All patients with APS clinical manifestations had an elevated aGAPSS. Higher aGAPSS were seen in patients who experienced thrombosis than those with only pregnancy morbidities. Previously reported differences in aGAPSS among patients with recurrent thrombosis and patients with a single thromboembolic event were not observed in this cohort of Chinese APS patients. aGAPSS may be a potential quantitative tool for APS related clinical manifestations. However, further clinical examination and validation in a large multicenter and multi-ethnicity cohort with control is warranted. Disclosure: Y. Zuo, None; C. Li, None; D. R. Karp, None; Z. Li, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/clinical-and-epidemiological-correlates-ofthe-adjusted-global-anti-phospholipid-syndrome-score-in-a-large-cohort-of-chinese-aps-patients
Abstract Number: 2184
Non-Criteria Clinical Manifestations in Antiphospholipid Syndrome: Clinical Behavior and Association with Damage Accrual Gabriela Hernandez-Molina1, Cindy Maldonado-Garcia1 and Antonio R. Cabral2, 1Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico, 2Immunology & Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Antiphospholipid Syndrome: Clinical Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: The relevance of non-criteria clinical manifestations of antiphospholipid syndrome (APS) has been less studied than its thrombotic and obstetric features. The aim of this study was to evaluate the relationship of APS non-criteria clinical manifestations with antiphospholipid antibodies and damage accrual. Methods: We retrospectively included 176 patients with APS according to Sydney or Alarcon-Segovia’s criteria. We registered demographics, antiphospholipid antibody profile, use of prednisone and immunosuppresors, thrombotic and obstetric
manifestations as well as the following so-called non-criteria clinical manifestations: cutaneous (livedo reticularis, skin ulceration,) hematological (thrombocytopenia, hemolytic anemia), renal (microangiopathy, proteinuria or renal impairment), heart valve disease, and neurological (chorea, migraine, seizures and myelitis). We scored a modified SLICC index where we also included the variables racemous livedo, adrenal insufficiency, placing of Greenfield filter and sclerosis multiple-like disease. We used descriptive statistics and logistic regression and reported OR with 95% CI. Results: Seventy-eight percent of our patients were women with a mean age of 43.1 ± 14.7 years and median follow-up of 6.7 years. We observed thrombosis in 73%, obstetric features in 20% and 64% had non-criteria clinical manifestations (not exclusive groups). 73 patients (41.4%) had both thrombosis and a non-criteria clinical manifestation (10 concomitant, 42 post-thrombotic and 21 pre-thrombosis).The frequency of the non-criteria clinical manifestation were: hematological 64%, cutaneous 33%, neurological 27%, cardiological 8.2% and renal 6.4%. The univariate analysis showed that the prevalence of LA was higher in the non-criteria clinical manifestation group (53.2% vs. 69.5%, p=0.03). This group also used more prednisone (35.8% vs.1%, 99th percentile of 100 healthy controls and high positive was defined as double that level. Data on VE (venous or arterial thrombosis or coronary disease) and pregnancy were obtained from medical records and patient interviews. Fisher's exact test was used to analyse statistical associations between particular serological profiles and VE or PM. Results: The mean (SD) age of the 501 patients was 30 (12.2) years, 91% were female and 61% white. In the early disease samples, 68 were positive for anti-CL, 24 for anti- beta2GPI and 146 for anti-DI. 30 patients were double-positive for two of these aPL and 9 were triple-positive. Using higher cut-off levels, 31, 6 and 36 were high-positive for anti-CL, anti- beta2GPI and anti-DI respectively. Mean follow-up time post-sample was 12.1 years (max 36 years). Full data on VE and PM were available for 338 and 275 patients respectively. Table 1 shows associations between particular serological profiles and occurrence of VE or PM.
Conclusion: 38% of patients were positive for one or more aPL in early disease but only 15% showed high positivity. Being double or triplepositive was most strongly associated with VE (but not PM) – 40% of the double/triple positive patients suffered VE in the follow-up period. Positivity for anti-beta2GPI was also associated with VE. High positivity for anti-DI showed the strongest association with PM. Table 1 – Association of different serological profiles in early disease with VE or PM (* signifies statistically significant association3 months prior but no ARTH) (n=352). Impact on work for pay was measured by ‘yes’ to: 1) do arthritis or joint symptoms "now affect whether you work for pay or not," 2)"the type of work," or 3)"the amount of work" you do? Only those employed were asked type and amount. We estimated prevalence of each impact for ARTH and CJS separately and compared characteristics using weighted proportions with 95% confidence intervals (CI). All reported proportions represent statistically significant differences based on non-overlapping CIs. Results: Overall, CJS were younger, employed more (68% vs 54%), disabled less (11% vs 22%), and had less reports of losing ≥1 workday (5% vs 13%) or activity limitations due to symptoms (33% vs 55%) compared with ARTH. Fair/poor health (19% vs 33%), severe joint pain (13% vs 31%), and daily pain (42% vs 59%) were less common among CJS vs ARTH. Impact on whether one works and type of work were both higher for ARTH vs CJS (36% vs 20% and 43% vs 30%, respectively). Impact on amount of work was not significantly different between groups. Among ARTH greater proportions of females (35% vs 16%), those with some college education (37% vs 18%), and the obese (41% vs 23%) reported impact on whether one works
than CJS counterparts. Also among ARTH greater proportions with no activity limitations (55% vs 40%), no depression (26% vs 13%), no anxiety (21% vs 11%), no severe joint pain (23% vs 14%), and no bathing/dressing limitations (20% vs 9%) reported impact on whether one works compared with CJS. Conclusion: Work impacts are high among both ARTH and CJS, despite different group patterns. ARTH work impacts are common even without severe joint pain or physical limitations. Given the economic importance of work, interventions for both groups are warranted, but ARTH identifies a priority population. Disclosure: K. A. Theis, None; M. Boring, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/impacts-on-work-arthritis-vs-chronic-jointsymptoms-without-arthritis
Abstract Number: 2281
The Prediction of Fatigue in Early Rheumatoid Arthritis Patients Margot Walter1, T. Martijn Kuijper2, Mieke Hazes2,3, A.E.a.M. Weel4 and J.J. Luime5, 1Rheumatology, Erasmus Medical Center, Rotterdam, Netherlands, 2Rheumatology, Erasmus University Medical Center, Rotterdam, Netherlands, 3Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands, 4Department of Rheumatology, Maasstad Hospital, Rotterdam, Netherlands, 5Department of Rheumatology, Erasmus Medical Centre, Rotterdam, Netherlands First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Epidemiology and Public Health Poster (ARHP) Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM The prediction of fatigue in early Rheumatoid arthritis patients Background/Purpose: Rheumatoid arthritis-related fatigue is a common problem with a high impact on patients. How fatigue develops over time since early diagnosis of RA is not well known. The aim of this study was i) to describe the pattern of the fatigue over time in patients with early RA under T2T ii) to identify predictive factors /determinants for evolution of fatigue over time stratified for baseline values of fatigue. Methods: Data from the tREACH study (treatment in the Rotterdam Early Arthritis Cohort) were used. This multi-centered trial compared different initiation treatment strategies in early RA patients. Patients completed VAS and FAS on fatigue, CORS, HADS, RADAI, SF-36 and were clinically assessed by DAS every 6 month. We stratified the patients into no fatigue (FAS values 10-21) and fatigued (FAS values 22-50) and assessed the evolution of fatigue over time and the covariates using a mixed linear model with time lag. Missing covariate data was imputed using a mixed linear model. Results: A total of 270 individuals classified as RA using the 2010 criteria, 246 could be stratified according to their baseline fatigue (24 had missing data). The sample resulted in a typical early RA population with a mean age of 53 years (SD 14.3 years) and 68% females, 73% rheumatoid factor and 77% anti-CCP antibodies positive. The percentage of patients with joint damage was 18%.The VAS fatigue was 51.4(SD 25.9) and the FAS 22.2 (SD 7.1). High fatigue at baseline was univariate associated with higher levels of the CORS, high levels of depression and anxiety, a worse physical health (SF-36) and more swollen and tender joints.Over time fatigue decreased slightly with 2-7% on average as shown in figure 1. Significant determinants for the prediction of fatigue in the univariate and multivariate analysis are presented in table 1. Conclusion:
About half of the early RA patients reported high levels of fatigue at baseline which for most of them consisted over time. Only better reported physical health (SF36) predicted change of fatigue. Patients with low fatigue at baseline were more likely to develop fatigue over time if they were women, had more tender joints, were more anxious and had a worse Physical SF36 scores. Figure 1 evolution over time of fatigue
s Table 1 Univariate and multivariate analysis FAS (≤21) FAS (>22) Fatigud (≤21) FAS (>22) divided into two groups Univariate analysis Multivariate analysis β-Coeff.(CI95%) β-Coeff.(CI95%) β-Coeff.(CI95%) β-Coeff.(CI95%) Sex -2.59** -1.17 -2.21** (-3.59- Disclosure: M. Walter, None; T. M. .833) Kuijper, None; M. Hazes, None; A. E. A. (-4.21--0.97) (-3.61-1.27) M. Weel, None; J. J. Luime, None. Age -0.06** -0.023 View Abstract and Citation Information (-0.12- -0.003) (-0.10-0.05) Online - http://acrabstracts.org/abstract/theWork 1.24 1.165 prediction-of-fatigue-in-early-rheumatoidarthritis-patients (-0.40- 2.89) (-1.00- 3.33) Education 0.18 0.44 Abstract Number: 2282 (-0.83- 1.20) (-1.03- 1.92) Dutch -1.91 0.47 CRP
(-2.69- 3.65) -0.018
(-0.06- -0.004) -0.76**
(-0.05-0 .01) 0.11
(-1.36- -0.15) 0.098*
(-0.80- 1.02) 0.027
(-0.07- -0.007) 0.010*
(-0.13- 0.06) 0.01
(-0.05-0 .01) -0.19
(0.031-0.66) Hads 0.18 depression (-0.04-0 .41) Hads 0.24* anxiety
Tender joints Swollen joints VAS global
( -0.22-0 .28) 0.24
“Doing Every-Day Life” with Primary Sjögren’s Syndrome: Factors Predicting Difficulties Performing Daily Activities and Taking on Life Roles
Katie Hackett1, Dennis W Lendrem2, Tim Rapley3, Katherine Deane4, Vincent Deary5, Simon Bowman6, Julia Newton7, Wan-Fai Ng8 and on behalf of the United Kingdom Primary Sjogren's Syndrome Registry, 1Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Institute of Cellular Medicine (Musculoskeletal Research Group), NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals Foundation Trust and Newcastle University, Newcastle upon Tyne, United Kingdom, 3Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom, 4University of East Anglia, Norwich, United
anxiety Coping pain Coping limitations
(0.04-0 .44) 0.08
(0.009-0.15) (-0.14-0.093) Physical -0.07* 0.097* -0.08** health ( -0.13- -0.013) (0.015-0.18) (-0.15- -0.02) (SF36) Mental -.020 -0.021 health (SF (-0.09-0.05) (-0.11-0 .07) 36) Level of significance *p=0.05 /**p=0.01/ ***p=0.001 Cut point for FAS ≤21 no fatigue/ >22 fatigue
Kingdom, 5School of Health Psychology, Northumbia University, Newcastle upon Tyne, United Kingdom, 6Rheumatology Dept, University Hospital Birmingham, Birmingham, United Kingdom, 7Newcastle University, Newcastle upon Tyne, United Kingdom, 8Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Epidemiology and Public Health Poster (ARHP)
Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: Primary Sjögren’s Syndrome (pSS) is an autoimmune disease which targets secretory glands and results in dryness. In addition pSS patients frequently experience symptoms of fatigue, pain, low mood and have difficulty performing daily activities and subsequently have poor quality of life. There is currently no curative treatment and medical interventions focus on the symptomatic management of dryness. The aim of this study is to identify independent predictors for each of the SF-36 domains in order to identify targets for future therapy interventions with pSS patients. The goal is to identify potential interventions to be delivered by non-medical health care professionals in order to improve the ability to perform daily activities, facilitate taking on life roles and improve quality of life. Methods: 149 PSS patients diagnosed according to the American European Consensus Criteria were recruited from 12 sites across England. Participants completed the SF-36 questionnaire and measurements of anxiety and depression (Hospital Anxiety and Depression Scale HADs), functional status (ImprovedHAQ), pain (visual analogue scale (VAS), fatigue (VAS), mental fatigue (VAS), dryness (VAS), cognitive failures (Cognitive Failures Questionnaire) and recorded their age and disease duration. Significant correlates of each of the SF-36 domain were identified and multiple regression analysis performed for each of the domains to determine partial regression coefficients. Model robustness was determined by hierarchical regression analysis testing the sensitivity of the model to the order of inclusion. Results: With one exception, PSS patients scored significantly worse than the norm-based scores for all domains of the SF-36, including Physical Functioning, Role Physical, Bodily Pain, Vitality, Social Functioning, Role Emotional and Mental Health (p 3 times. User satisfaction was mod to high across sections (median varying from 6.0 to 7.3 on 1-10 scale), with highest satisfaction with the disease activity section. In preliminary analyses of 6-month data, no significant differences were observed in consumer effectiveness attributes or in health status. Perceived benefits of the AHJ mentioned in interviews included enhanced self-awareness, ability to see relationships between symptoms and trends over time in symptoms and disease activity, which was felt to facilitate medical-decision making during medical visits. Barriers to use included lack of perceived need when disease was stable, well-controlled or longstanding (stating they would have used it at disease onset), internal factors (e.g. fatigue, unwillingness to focus on disease, denial), external factors (lack of time due to life events). Those who found AHJ beneficial tended to use it more frequently. Conclusion: Our proof of concept study shows that people were satisfied with the AHJ, but many did not use it frequently for a variety of reasons. No difference between groups were detected in consumer attributes or health status in preliminary analyses; however, the 6-month timeline might be short to expect such difference. A number of benefits were identified, esp. in people who used it frequently.
Disclosure: D. Lacaille, None; E. Carruthers, None; B. van As, None; C. H. Goldsmith, None; H. Horlock, None; L. Li, None; A. F. Townsend, None; B. Mitchell, None; P. Adam, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/proof-of-concept-study-of-the-arthritis-healthjournal-an-online-tool-to-promote-self-monitoring-in-people-with-rheumatoid-arthritis-ra
Abstract Number: 2335
How Much Does Fatigue Contribute to the Physician and Patient Global Estimates in Different Rheumatic Diseases? Analysis from Routine Care on a Multidimensional Health Assessment Questionnaire (MDHAQ) Isabel Castrejón1, Elena Nikiphorou2, Ruchi Jain1, Annie Huang1, Joel A. Block3 and Theodore Pincus1, 1Rheumatology, Rush University Medical Center, Chicago, IL, 2Rheumatology, Addenbrooke's Hospital, Cambridge, United Kingdom, 3Rush University Medical Center, Chicago, IL First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Health Services Research Poster III: Patient Reported Outcomes, Patient Education and Preferences Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: Fatigue is an important problem for many patients with rheumatic diseases. Fatigue is associated with disease severity, psychological distress, and a poorer quality of life in rheumatoid arthritis (RA) (1), but the extent to which the level of fatigue may contribute to disease activity is controversial. A fatigue 0-10 visual analog scale (VAS) is included on a multidimensional health assessment questionnaire (MDHAQ). We analyzed possible associations between fatigue and global estimates of disease activity according to the patient (PATGL) and the physician (DOCGL) in patients with different rheumatic diseases seen in routine care. Methods: All patients seen in one academic clinical setting complete a 2-page MDHAQ in 5-10 minutes in the waiting area, prior to seeing the rheumatologist in the infrastructure of usual care. The MDHAQ includes physical function (FN) in 10 activities of daily living, three 0-10 visual analog scale (VAS) for pain (PN), PATGL, and fatigue (FT), and demographic data. Four activity categories were defined for PATGL and DOCGL: 6 for ‘high’. Median values for fatigue and interquartile range (IQR) were compared in the 4 PATGL and DOCGL categories in 4 diagnostic groups: rheumatoid arthritis (RA), osteoarthritis (OA), systemic lupus erythematosus (SLE), and fibromyalgia (FM), using oneway analysis of variance; Kruskall-Wallis tests of significance were performed. Results: The study included 612 consecutive patients, 173 with RA, 199 with OA, 146 with SLE and 94 with FM. Median fatigue scores were significantly higher in FM (7, IQR=5-8) p18, with a baseline (12 months) diagnosis of stage 3/4 chronic kidney disease (CKD) and CVD (coronary artery disease (CAD), cerebrovascular disease (CBV) and peripheral vascular disease (PVD)) or heart failure were selected from the MarketScan® databases (January 2009-June 2013) upon initiating urate lowering therapy (ULT) with either allopurinol (ALO) or febuxostat (FBX). Patients were followed until disenrollment, discontinuation of the qualifying ULT or use of the alternate study agent. MCE included myocardial infarction, stroke, transient ischemic attack, non-traumatic, lower extremity (LE) amputation or coronary, cerebrovascular or LE revascularization. MCE incidence was measured per 1000 person-years (PY). Cox proportional hazards models assessed MCE risk as a function of age, gender, region, payer, CKD stage, exposure to other anti-gout medications (NSAID, colchicine, steroids, probenecid), recent CVD hospitalization and a history of CAD, CBV, PVD, heart failure (HF), diabetes or hyperlipidemia. Results: A total of 2,426 patients (2056 ALO, 370 FBX) met eligibility criteria (63% male; mean age 73±11). Two thirds of patients had a history of CAD, 18% CBV and 23% PVD. There were no significant differences in CVD type by cohort. Half of patients also had HF and 73% had stage 3 CKD at the time of initiation. A total of 162 MCE occurred during follow-up in 3.8% and 7.2% of FBX and ALO cohorts respectively. A total of 80 patients (3.3%) had a CAD specific MCE, 51 (2.1%) a PVD specific event and 38 (1.6%) a CBV specific event. The MCE rate per 1000 PY (95% CI) in the FBX cohort was 51.8 (28-87) as compared to 99.3 (84-117) in the ALO cohort. Cox model results suggest significantly increased MCE risk (any MCE) among patients with baseline PVD (HR 2.7; 95% CI 1.9 – 3.7, p–488.1 to ≤–13.6 U/ml; Q2 >–13.6 to ≤0.0 U/ml; Q3 >0 to ≤8.8 U/ml; Q4 >8.8 U/ml. The mean reductions in disease activity based on CDAI, SDAI and joint counts were greatest for Q1 (Figure 2). Similar patterns of change in disease activity were observed after controlling for baseline covariates in multivariate analysis. Conclusion: We observed that ACPA titers change over time and ACPA increase is primarily observed in ACPA+ pts with higher ACPA values at baseline. Pts with reduction in ACPA show a numerically greater reduction in disease activity levels.
Disclosure: E. Alemao, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; K. Gandhi, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; C. Iannaccone, None; M. Frits, None; J. Coblyn, None; N. Shadick, Amgen, Questcor, Crescendo Biosciences, UCB, Bristol-Myers Squibb, 2; M. Weinblatt, Amgen, Abbvie, Bristol-Myers Squibb, Lilly, Novartis, Merck, Pfizer, Roche, Crescendo, Myriad Genetics, UCB, 5,Bristol-Myers Squibb, Myriad Genetics, UCB, 2. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/evaluation-of-anti-cyclic-citrullinated-peptideautoantibody-levels-in-clinical-practice-and-its-association-with-disease-activity
Abstract Number: 2664
Flares Occur Frequently in RA Patients Undergoing Arthroplasty Susan M. Goodman1, Rivka Friedlander2, Caroline Figgie2, Anh Hoang1, Kathleen Andersen3, Alessandra B. Pernis4, Cristina T. Rozo5, Edward F. DiCarlo6, Mark P. Figgie7, Laura T. Donlin8 and VP Bykerk3, 1Rheumatology, Hospital for Special Surgery, New York, NY, 2Research, Hospital for Special Surgery, New York, NY, 3Hospital for Special Surgery, New York, NY, 4Autoimmunity & Inflammation, Hospital for Special Surgery, New York, NY, 5535 East 70th Street, Hospital for Special Surgery, New York, NY, 6Laboratory Medicine, Hospital for Special Surgery, New York, NY, 7Orthopaedics, Hospital for Special Surgery, New York, NY, 8Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: RA patients are at risk for disease worsening (flare) after joint surgery, as medication is withdrawn to mitigate infection risk. We aimed to describe rates and characteristics of RA flare within 6 weeks of total hip (THA) and total knee arthroplasty (TKA). Methods : RA patients undergoing TKA/THA were queried every week about any change in RA status including pain and function (MDHAQ, HOOS/KOOS ADL). Baseline (BL) characteristics, BL and 6 week DAS-28, were collected. RA Flare was defined by Patient Report (yes/no, “Are you in a flare?”). Flare classification was determined by concordance between patient report of flare and MD assessment of flare, by chart review including joint counts, excluding the surgical joint. Medication use was standard of care: biologic DMARDs stopped; steroids and MTX continued. Results : Of 37 RA pts recruited, most were female, white and had undergone THA (Table 1). Mean (SD) time to flare was 2.9(2.0) wks in 23/37 (62%) patients, with a self-rated flare severity of 6.3(2.4), duration >4 days in 74%. All but 6 stopping biologics flared. Numerically, more flarers took steroids, MTX and biologics. Disease activity at baseline and 6 weeks remained moderate for both groups (Table 2). Though numerically higher in flares disease activity and function at BL and change over 6 weeks was similar. At 6 weeks, patients reporting flare had significantly higher tender joint counts [RADAI 14.5(8.3) vs. 7.6(6.1), p=0.02], rescored to remove the surgical joint [RADAI 13.3(7.7) vs. 6.5(6.1), p=0.02]. Worse MDHAQ [4.0(1.7) vs. 2.9(1.2), p=0.07] and RAPID3 [13.8(5.3) vs.
14.7(8.2), p=0.09] approached significance. Conclusion: Post-op flares are frequently reported, and rated as severe in RA patients undergoing THA/TKA. Numerically, flares are more frequent in patients stopping biologics. Increased RA related worsening joint pain and function seen in those whose RA worsens after surgery may contribute to poor long-term outcomes for RA patients undergoing THA/TKA. Further studies of post-op flare are needed. This study was supported by the Clinical Translational Science Center (CTSC) (UL1-TR000457-06)
Disclosure: S. M. Goodman, National Institutes of Health, 2; R. Friedlander, None; C. Figgie, None; A. Hoang, None; K. Andersen, None; A. B. Pernis, Kadmon Corporation, 2; C. T. Rozo, None; E. F. DiCarlo, None; M. P. Figgie, None; L. T. Donlin, None; V. Bykerk, National Institutes of Health, 2. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/flares-occur-frequently-in-ra-patients-undergoingarthroplasty
Abstract Number: 2665
Improved Flare/ Remission Pattern in Rheumatoid Arthritis over the Recent Decades
Elena Myasoedova1, Sherine E. Gabriel2, Eric L. Matteson3, John M. Davis III4 and Cynthia S. Crowson5, 1Internal Medicine and Rheumatology, Mayo Clinic, Rochester, MN, 2Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 3Rheumatology, Mayo Clinic, Rochester, MN, 4Division of Rheumatology, Mayo Clinic, Rochester, MN, 5Health Sciences Research, Mayo Clinic, Rochester, MN First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: Flare or episodic worsening of disease activity is an important aspect of the disease experience for patients with rheumatoid arthritis (RA), with significant impact on quality of life, well-being, joint damage and comorbidity. Improving trends towards lower RA disease activity have been suggested in recent years as compared to previous decades. However, long-term data on flare and remission rates in RA over calendar time are lacking. We aimed to assess trends in the occurrence of flares and remission in RA over the last decades. Methods: In a population-based cohort of patients with RA (age≥30 years; 1987 ACR criteria met in 1988-2007) we performed a retrospective medical records review of each clinical visit to estimate flare and remission status. RA flare was defined as any worsening of RA activity leading to initiation/change/increase of therapy (OMERACT 9). Remission was defined as the absence of disease activity (i.e. tender joint count [TJC] = 0 + swollen joint count [SJC] = 0 + ESR ≤ 10 mm/hr) (OMERACT 7). All subjects were followed until death, migration or July 1, 2012. Flare and remission rates were calculated as the percentage of visits in flare or remission in each calendar year. Time spent in flare was calculated as days in flare divided by days of follow-up in each calendar year. Results: The study included 525 RA patients (mean age 54.5 years; 71% female) with mean follow up of 10.1 years. Flare/ remission status was collected for a total of 15,649 clinical visits. Patients were flaring in 2829 (18%) visits and were in remission in 1545 (10%) visits. The median duration of flare was 2.4 months (Q1 1, Q3 5.4 months). The figure shows trends in flare and remission occurrence in RA patients over time. There has been a statistically significant decline in the RA flare rate over calendar time, from 32% of visits per year in 1990 to 15% of visits per year in 2010 (p2 cm between the 2 assessments. Linear regression models evaluated predictors of PGA and EGA, and relative importance weights were calculated for their proportionate contribution to PGA and EGA variance. Logistic regression models interrogated predictors of both patient and physician higher ratings respectively.
Results: Our models explained 66% of variability in PGA and 83% of the variability in EGA. Main, multivariate determinants for PGA were fatigue (23.7%), pain (21.2%), depression (18%), and sedimentation rate- ESR (3.2%). EGA was mainly predicted by swollen joint counts (44.4%), tender joint counts (30.2%), ESR (5.2%) and fatigue (3.5%). Concordance was observed in 142 (43%), higher patient ratings in 147 (44%), and higher physician ratings in 44 (13%). Fatigue and pain predicted higher patient ratings, while swollen joints, tender joints, and prednisone use predicted higher physician ratings (table 1). At follow up, EGA improved in 31.7%, remained unchanged in 50.9% and worsened in 17.4%. Respective trends for PGA were 28.6%, 44.1% and 27.3%. The lowest concordance was seen for worsening disease, where PGA showed only 27% concordance with the EGA, compared to 59% and 52% for unchanged or improved disease respectively. Conclusion: Highly divergent parameters shape patients' and physicians' perceptions of disease activity in Latinos with RA in the US; fatigue and pain contribute mainly to higher patient assessments, while swollen and tender joint counts predict higher physician assessments. Patient education of what determines long-term disability, and a better physician grasp of the patient perspective will likely foster shared decision-making and compliance with treat to target initiative. Table 1: Predictors of discordant Patient –Physician Assessments of global disease activity Higher PGA (PGA - EGA > 2cm) Unadjusted Adjusted OR OR (95% (95% CI) CI) (1.00 Age 1.02 1.04) (0.61 Gender 1.29 2.73) Disease (0.95 0.98 duration 1.01) (0.19 RF positive 0.46 1.09) (0.31 CCP positive 0.64 1.34) (0.66 Erosions 1.04 1.65) (0.75 IAD present 1.25 2.10) (1.01 (0.38Fibromyalgia 1.87 0.90 3.48) 2.10) (0.89 (0.79 n-TJC 0.94 0.87 0.99) 0.95)** (0.73 (0.54 n-SJC 0.80 0.64 0.88) 0.75)*** (0.99 ESR 1.00 1.01) (0.75 Prednisone 1.23 2.02) (0.77 n-DMARDs 0.97 1.23) (0.73 Biologics 1.17 1.88) (1.35 (0.84HAQ-DI 1.80 1.31 2.41) 2.04) (1.53 (1.23 Pain-VAS 2.07 2.06 2.79) 3.46)*** (1.06 (0.99 PHQ-9 1.10 1.05 1.15) 1.12) (1.16 (1.12 FACIT 1.26 1.30 1.37) 1.49)***
Higher EGA (EGA - PGA *p2 erosions were displayed along with the mean bones. (Figure 1) Results: Erosions were present in low numbers of patients. In 18 patients there were no erosions visible in MR despite reported radiographic erosions. Over half had only 0 to 2 bones with an erosion. Erosions exhibited a clear spatial pattern. In the metacarpals, the erosions were most prevalent in MCP2 and 3 (Table 2). In the wrist, there were typically 20 erosions per bone for half of the bones; the trapezium, trapezoid and proximal metacarpals had ~10. Erosions occurred at consistent sites, with only one or 2 sites within each bone where the erosion was found in >2 patients. Conclusion: This is the first study to provide an accurate 3D visualisation of erosion sites in early RA. Erosions occurred at only a small number of entheseal sites. Erosions in the metacarpals occurred in the area containing the collateral ligament and capsular attachments. In the wrist, the erosions were located primarily on the palmar side of the bone, and had a more complex arrangement. Although multiple ligament, capsular and tendon attachments exist in close proximity on each bone, we observed that erosion sites were usually those in which there was a deep attachment site in non-eroded patients. This suggests that the attachments which will generate an erosion are those which experience the highest mechanical load. Further careful study will be required to pursue the detail of these anatomical locations, and will significantly help our understanding of the pathogenesis of RA erosions.
Disclosure: M. A. Bowes, None; G. Guillard, None; Z. Xie, None; B. Wilkinson, Pfizer Inc, 1,Pfizer Inc, 3; P. G. Conaghan, Abbvie, BMS, Novartis Non-remunerative, 5,Abbvie, BMS, Janssen, Roche, 8. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/3d-location-of-erosions-in-an-early-rheumatoidarthritis-population-an-mri-study-using-statistical-shape-models-with-implications-for-pathogenesis
Abstract Number: 2707
An in Vitro Bovine Bone Chip Model with Micro-CT: A Model for the Assessment of Autoantibody Mediated Bone Resorption Manpreet Kaur Sethi1, Anand Dusad1, Andy Hollins2, Carlos D. Hunter3, Michael J. Duryee3, Ted R. Mikuls2, Geoffrey M. Thiele4 and Ellen M. Gravallese5, 1Rheumatology, University of Nebraska Medical Center, Omaha, NE, 2University of Nebraska Medical Center, Omaha, NE, 3Internal Medicine Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, 4Omaha VA Medical Center and University of Nebraska Medical Center, Omaha, NE, 5Lazare Research Bldg Ste 223, University of Massachusetts Medical School, Worcester, MA First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: Anti-citrullinated protein antibodies (ACPAs) are specific to rheumatoid arthritis (RA) and are associated with disease severity. Although ACPAs are associated with disease progression, mechanisms driving this relationship are not well understood. The objective of this study was develop an in vitro model incorporating bovine bone chips and micro-CT (µ-CT) to investigate the effects of ACPA on bone remodeling. Methods: PBMCs were isolated from the blood of normal controls. Osteoclasts (OCs) were generated by culture in α-MEM media containing 1% penicillin/streptomycin and 10% heat inactivated FBS along with RANKL (1 ng/ml) and MCSF (10 ng/ml) for 14 days. Sera from ACPA positive RA patients was obtained and IgG was isolated using Staph Protein G columns. Antibody to citrullinated type II human collagen (Cit-C-II) was purified using CNBR Sepharose beads coupled with Cit-C-II. F(ab')2 and Fc fragments were generated using pepsin columns and were added to differentiated OCs in the presence and absence of C-II and Cit-C-II and incubated with bone chips for 3 days (n=3 chips/group). Bone chips were then scanned with µ-CT for bone mineral density (BMD) and pit volume (PV). Bone specific alkaline phosphatase (BAP) and cathepsin-K (CTPK) were measured on media using ELISA. BAP/CTPK ratios served as the primary measure of bone turnover. Results: Activated OCs in the absence of ACPA increased PV and decreased BMD (Figure), although these differences did not reach
significance. Compared to OCs stimulated with F(ab')2 + C-II + Cit-C-II, the substitution of Fc fragments for F(ab')2 led to significant increases in BAP (4.24 vs. 1.89 ng/ml, p=0.006) and CTPK (7.07 vs. 2.83 ng/ml, p = 0.011); BAP/CTPK ratio was higher, but not significantly, in OCs incubated simultaneously with Fc and F(ab')2 antibodies along with C-II and Cit-C-II as compared to OCs alone (Figure; p= 0.181 and p= 0.071, respectively). Across groups, BAP values were positively correlated with PV (r= 0.52, p=0.015). Addition of the F(ab')2 or Fc fragments led to a numeric increase in PV and decreased BMD, although differences compared to OCs alone did not reach significance. Conclusion: The differential effects of Fc and F(ab')2 fragments of anti-Cit-C-II antibody along C-II and Cit-C-II antigens suggests that the action on bone could be mediated by both the type of antibody fragments and the amount and type of antigen present. Additional studies with a larger number of samples will be needed to perform more robust statistical comparisons including the evaluation of alternative doses and different ACPA. This novel model, incorporating bovine bone chips with µ-CT, appears to be a practical and reproducible approach for studying the osteoimmunology of ACPA and citrullinated antigens.
Disclosure: M. K. Sethi, None; A. Dusad, None; A. Hollins, None; C. D. Hunter, None; M. J. Duryee, None; T. R. Mikuls, None; G. M. Thiele, None; E. M. Gravallese, None. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/an-in-vitro-bovine-bone-chip-model-with-micro-cta-model-for-the-assessment-of-autoantibody-mediated-bone-resorption
Abstract Number: 2708
Correlation of Peripheral Blood Th-17 and Th-1 with Synovitis and Osteitis By MRI in Recent Onset Rheumatoid Arthritis Sukesh Edavalath1, Ankita Singh1, Namita Mohindra2, Sunil Kumar2 and Ramnath Misra1, 1Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, 2Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: An increased expansion of Th17 cells in the synovial membrane have shown to play a key role in causing persistent synovitis leading to cartilage and bone destruction in RA. MRI is superior to conventional X-rays in detecting erosions in early disease. In this study we sought to see the association of level of peripheral circulatory Th-17 and Th-1 cells with MRI changes in RA Methods:
RA patients satisfying ACR Criteria 2010 with active disease (DAS28 >3.2) and within 3 years of onset who had not received prior DMARDs or steroids were recruited. MRI of dominant hand and wrist was done using 0.2 Tesla extremity MRI and was scored using OMERACT RA MRI Scoring system 2002 by two radiologists. Peripheral blood Th1 (CD3+ CD4+ IFNγ +) and Th17 (CD3+ CD4+ IL17+) were enumerated by flow cytometry. Th-1and Th-17 levels were measured in 25 healthy controls. Statistical analysis was done by non-parametric tests using SPSS statistics 21version software. Results: Thirty-two consecutive patients (26 females and 6 males) with RA after obtaining consent were included. The median age at presentation was 38.5 years (Range 19 – 65 years) with median disease duration of 11.5 months (Range 1-36 months). The median DAS 28 score was 4.35 (Range 3.22 – 6.24). All the patients were seropositive. MRI evaluation revealed synovitis in 93.8%(30/32), Osteitis in 31.3%(10/32) and erosions in 75% (24/32) of patients. On subgroup analysis erosions were present in 67% (12 /18) of cases of early (≤ 1year) RA and in 86% (12/14) of established (> 1 year) RA. OMERACT RA MRI scoring revealed a significantly (p10 years (p10 yrs (p=0.005). These differences were attenuated in multivariable models and lost significance. The proportion of patients remaining on abatacept at 1 year among those with 0–2 years' disease duration was 70% compared with 63.9% of those with >10 years' disease duration (p=0.07). Conclusion: Treatment with abatacept was associated with significantly greater improvement in those with shorter disease duration in unadjusted analyses. This significance was lost in adjusted models, but the trend remained. Further exploration is needed to assess whether earlier treatment with abatacept is independently associated with better outcomes.
Table 1. Baseline characteristics Disease duration, years 0–2 3–5 N=243 N=313 56 (13.9) 57 (13.3) 195 (80.2) 255 (81.5)
6–10 >10 p-value Baseline characteristics N=431 N=759 Mean age (SD), years 57.2 (12.6) 61.7 (11.5) 0.001 Female, n (%) 349 (81.0) 632 (83.3) 0.640 Smoking status 0.020 Current, n (% of m*) 37 (15.4) 68 (21.8) 77 (17.9) 103 (13.6) Mean BMI (SD), kg/m2 30.0 (6.9) 29.9 (6.9) 29.5 (6.7) 29.5 (7.1) 0.22 † 0.001 Work status, n (% of m*) Full time 114 (46.9) 102 (33.2) 159 (37.1) 209 (27.7) Part time 26 (10.7) 32 (10.4) 41 (9.6) 70 (9.3) Not working outside home 29 (11.9) 38 (12.4) 48 (11.2) 68 (9.0) Student 4 (1.6) 10 (3.3) 9 (2.1) 13 (1.7) Disabled 20 (8.2) 47 (15.3) 72 (16.8) 158 (21) Retired 50 (20.6) 78 (25.4) 99 (23.1) 236 (31.3) Medicare, n (%) 63 (25.9) 101 (32.3) 142 (32.9) 363 (47.8) 0.001 Median mHAQ (IQR) 0.38 (0.75) 0.38 (0.75) 0.38 (0.75) 0.5 (0.75) Median CDAI (IQR) 20.5 (18.2) 19.8 (19.5) 19 (19.6) 18.3 (19.2) 0.45 Number of prior biologics/small 0.001 molecules, n (%) 0 107 (44.0) 45 (14.4) 50 (11.6) 79 (10.4) 1 85 (35.0) 130 (41.5) 161 (37.4) 244 (32.1) 2 42 (17.3) 105 (33.5) 132 (30.6) 246 (32.4) 3+ 9 (3.7) 33 (10.5) 88 (20.4) 190 (25.0) IQR=interquartile range; mHAQ=modified Health Assessment Questionnaire *m=number of patients with non-missing data; †P-value for number disabled vs others. Table 2. Outcomes
Primary outcome Δ in CDAI Adjusted Δ in CDAI Model 1* Adjusted Δ in CDAI Model 2† Secondary outcome Unadjusted achievement of LDA/remission‡
Unadjusted likelihood of LDA Adjusted likelihood of LDA, Model 1* Adjusted likelihood of LDA,
Disease duration, years 0–2 3–5 N=243 N=313 Mean (SE) Mean (SE) –9.8 (0.93) –8.7 (0.82) –8.2 (0.80) –7.9 (0.68) –7.9 (0.81) –7.9 (0.68)
6–10 N=431 Mean (SE) –7.0 (0.70) –7.2 (0.58) –7.2 (0.58)
>10 N=759 Mean (SE) –5.9 (0.52) –6.6 (0.45) –7.0 (0.45)
n (%) N=206 92 (44.7)
n (%) N=259 89 (34.4)
n (%) N=336 111 (33.0)
n (%) N=585 176 (30.1)
(95% CI) 0.61 (0.43, 0.87) 0.78 (0.53, 1.13)
(95% CI) 0.53 (0.38, 0.003 0.74) 0.67 (0.46, 0.18 0.96)
(95% CI) (95% CI) Reference 0.65 (0.45, 0.94) Reference 0.80 (0.54, 1.18) Reference
p-value 2 wks of paid work (mean 13.3 vs 11.4 days), >2 wks of household duties (mean 18.9 vs 18.1 days), and mean 5.2 vs 5.6 days of social activities affected over previous month, respectively (Table A). At Wk52 in DMARD-naïve pts, greater improvements were reported in CZP+MTX arm vs PBO+MTX in household productivity, and in absenteeism and presenteeism (employed pts only) (Table B). Conclusion: DMARD-naïve pts with early severe RA and poor prognostic factors have a similar high burden on workplace and household productivity to that reported in established RA, which could lead to large financial burden for pts and society. CZP+MTX showed greater improvements at 1 yr in workplace and household productivity in DMARD-naïve pts with severe, active, progressive RA (≤1 yr since diagnosis), which could reduce the economic burden of this disease.
References: 1. Kavanaugh A. Arthritis Rheum 2009;61(11):1592–1600 2. Emery P. Ann Rheum Dis 2015;74(S2):712 3. Osterhaus J. Arthritis Res Ther 2009;11:R7
Disclosure: V. Bykerk, None; C. Bingham, UCB Pharma, 5; G. Burmester, Abbvie, MSD, Pfizer, Roche, UCB Pharma, 5; D. E. Furst, Gilead, 2,GlaxoSmithKline, 2,NIH, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Genentech and Biogen IDEC Inc., 2,UCB, 2,Abbvie, 5,Actelion Pharmaceuticals US, 5,Amgen, 5,Bristol-Myers Squibb, 5,Cytori, 5,Janssen Pharmaceutica Product, L.P., 5,Gilead, 5,GlaxoSmithKline, 5,NIH, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,Genentech and Biogen IDEC Inc., 5,UCB, 5,Abbvie, 8,Actelion Pharmaceuticals US, 8,Bristol-Myers Squibb, 2,Amgen, 2,Actelion Pharmaceuticals US, 2,Abbvie, 2,UCB, 8; X. Mariette, Pfizer, Roche, 2,Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma, 5; O. Purcaru, UCB Pharma, 3; B. VanLunen, UCB Pharma, 3; M. Weinblatt, Bristol-Myers Squibb, Genentech, Biogen IDEC Inc, GlaxoSmithKline, Human Genome Sciences Inc, MedImmune, Novo Nordisk, UCB Pharma, 2; P. Emery, Pfizer, MSD, AbbVie, UCB, Roche, Bristol-Myers Squibb, 5. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/reduction-of-disease-burden-on-workplace-andhousehold-productivity-following-52-weeks-of-treatment-with-certolizumab-pegol-in-combination-with-methotrexate-in-dmard-naivepatients-with-active-severe
Abstract Number: 2737
Consistency of Treatment Effects Across Different High-Risk Clinical Phenotypes in the Tofacitinib Clinical Program Jeffrey R. Curtis1, Ara Dikranian2, Alan Mendelsohn3, Koshika Soma4, Haiyun Fan3 and Chudy Nduaka3, 1University of Alabama at Birmingham, Birmingham, AL, 2San Diego Arthritis Medical Clinic, San Diego, CA, 3Pfizer Inc, Collegeville, PA, 4Pfizer Inc, Groton, CT First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Patients (pts) with RA often have comorbidities that may affect treatment response. This post-hoc analysis evaluated whether predefined clinical phenotypes influenced treatment response, as assessed by different efficacy and safety outcomes. Methods: Data from Phase 3 randomized studies of tofacitinib 5 mg BID in RA as monotherapy (ORAL Solo [NCT00814307], ORAL Start [NCT01039688]) or with background conventional synthetic DMARDs (csDMARDS; mainly methotrexate [MTX]) (ORAL Scan [NCT00847613], ORAL Sync [NCT00856544], ORAL Standard [NCT00853385]) were included. Pts in ORAL Start were MTX-naïve while pts in other studies had an inadequate response to biologic or csDMARDs, mostly MTX. Efficacy and safety of tofacitinib was evaluated in subgroups of monotherapy and combination therapy populations with different high-risk comorbidities: diabetes (history of diabetes and/or treatment with anti-diabetic medication at baseline [BL]); obesity (BMI ≥30 kg/m2) and hypertension (history of hypertension and/or treatment with antihypertensive medication at BL); or obesity and dyslipidemia (total cholesterol >2g/L and/or treatment with lipid-lowering medication at BL). Efficacy outcomes at Month 3 included the proportion of pts achieving low disease activity (DAS28-4(CRP) ≤3.2); ACR50 response; and mean change from BL in Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety outcomes included incidences of serious adverse events (SAEs) up to Month 3, discontinuations due to AEs, and serious infections (SIEs). Results: In total, 616 pts received tofacitinib 5 mg BID monotherapy (243 from ORAL Solo and 373 from ORAL Start) and 840 pts received tofacitinib 5 mg BID with background csDMARDs. Efficacy and safety outcomes by pt subgroups are presented in the Table. Tofacitinib 5 mg BID was similarly efficacious across different high-risk clinical phenotypes. Incidence rates for discontinuations due to AEs were numerically higher for the csDMARD group than the monotherapy group. Efficacy and safety outcomes in these subpopulations were within the ranges of the overall populations for the respective Phase 3 studies. Conclusion: These findings suggest that tofacitinib 5 mg BID, when administered as monotherapy or combination therapy, has a consistent efficacy and safety profile up to Month 3 in RA pts with different high-risk clinical phenotypes, such as diabetes. Although these pts are at high risk of further AEs, they appear to experience a short-term safety profile with tofacitinib similar to the overall clinical program population. Limitations include the relatively few pts in each clinical phenotype subgroup, and that the monotherapy group included MTX-naïve pts, whereas the csDMARD group included DMARD inadequate responders only.
Total, n/N (%)
Tofacitinib 5 mg BID Placebo*
Table. Efficacy and safety outcomes at Month 3 Monotherapy Background csDMARDs Diabetes Obese and Obese and Diabetes Obese and Obese and hypertension dyslipidemia hypertension dyslipidemia 47/616 77/616 121/616 68/840 108/840 166/840 (7.6)
(2.5) DAS28-4(CRP) ≤3.2
Tofacitinib 5 mg BID
[19.1, 48.5] 0/2
n/N (%) [CI]
[24.2, 42.2] 4/26
[17.6, 40.8] 2/31
[20.6, 39.3] 3/38
[17.9, 32.2] 2/76
[1.2, 31.7) 24/71
[4.4, 34.9] 39/114
[0.8, 21.4] 21/64
[1.7, 21.4] 28/99
[0.3, 9.2] 40/152
[23.4, 46.6] 2/20
n/N (%) [CI]
5 mg BID
[29.1, 60.1] 1/2
[23.0, 46.0] 4/21
[25.6, 43.7] 7/27
[21.6, 45.7] 4/31
[19.7, 38.2] 2/38
[19.5, 34.1] 6/76
[1.3, 98.7] -0.6 (0.6)
[5.5, 41.9] -0.6 (0.7)
[11.1, 46.3] -0.5 (0.7)
[3.6, 29.8] -0.5 (0.6)
[0.6, 17.8] -0.3 (0.5)
[3.0, 16.4] -0.4 (0.5)
-0.3 (0.7) 8.9
-0.2 (0.7) 1.2
-0.4 (0.7) 3.4
-0.3 (0.7) 14.3
-0.3 (0.5) 13.5
-0.2 (0.5) 12.3
HAQ-DI, mean change from BL (SD)
5 mg BID Placebo* Discont. due to AEs, Tofacitinib IR (95% CI) 5 mg BID Placebo* SAEs, n/N (%)
(3.4, 23.8) 0
Tofacitinib 5 mg BID Placebo*
5 mg BID Placebo*
(1.4, 8.2) 0
(2.7, 134.0) 2/77 (2.6)
(0.2, 8.6) 18.9
(7.9, 25.7) 0 5/68 (7.4)
(8.1, 22.3) 7.3
(8.1, 18.7) 3.7
(1.0, 51.5) 7/108
(0.5, 25.9) 8/166
(1.2, 12.0) 9.2
(3.0, 13.2) 0
(2.2, 21.1) 0
(0.3, 5.5) 0
(2.2, 8.9) 0
(1.3, 65.6) IR, incidence rate: pts with events/100 pt-years *For monotherapy studies, only ORAL Solo had a placebo arm
Disclosure: J. R. Curtis, Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 2,Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, 5; A. Dikranian, Pfizer Inc and AbbVie, 8,Pfizer Inc and AbbVie, 9; A. Mendelsohn, Pfizer Inc, 1,Pfizer Inc, 5; K. Soma, Pfizer Inc, 1,Pfizer Inc, 5; H. Fan, Pfizer Inc, 1,Pfizer Inc, 3; C. Nduaka, Pfizer Inc, 1,Pfizer Inc, 3. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/consistency-of-treatment-effects-across-differenthigh-risk-clinical-phenotypes-in-the-tofacitinib-clinical-program
Abstract Number: 2738
A Comparison of EQ5D Index from the UK, US, and Japan Preference Weights Model, and Mapping Algorithm from Clinical Outcomes in Patients with Rheumatoid Arthritis: Results from Golimumab Intravenous Study Chenglong Han1, Clifton O. Bingham III2, Rene Westhovens3, Michael Weinblatt4, Lilianne Kim5, Daniel Baker5, Steven Peterson6 and Elizabeth C. Hsia5,7, 1Outcomes Research, Janssen Global Services, LLC, Malvern, PA, 2Johns Hopkins University, Baltimore, MD, 3Rheumatology, UZ Gasthuisburg, Leuven, Belgium, 4Brigham & Women's Hospital, Boston, MA, 5Janssen Research & Development, LLC, Spring House, PA, 6Janssen Global Services, LLC, Malvern, PA, 7University of Pennsylvania, Philadelphia, PA First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: To compare the EQ5D index from the UK, US, and Japan preference weights models in patients with rheumatoid arthritis (RA), and to examine the relationship of each index with clinical outcomes for developing mapping algorithm. Methods: GO-FURTHER was a multicenter, randomized, placebo-controlled study. Adult patients with active RA were randomized to PBO + MTX (PBO group) or GLM (2mg/kg) plus MTX at wk 0, 2, and every 8 wk thereafter (GLM group). Patients in PBO group with 0) and dactylitis (Leeds dactylitis index [LDI], BL involvement = at least 1 digit affected and with a difference in circumference ≥10% compared to the contralateral digit). Observed data are presented for all pts originally randomized to CZP with and without prior anti-TNF exposure. Results: There were 409 pts randomized, 273 received CZP from Wk0, of whom 54 (19.8%) had prior anti-TNF exposure. Of the 273 CZPrandomized pts, 197 (72.2%) had BL nail psoriasis, 172 (63.0%) BL enthesitis and 73 (26.7%) BL dactylitis. BL scores for joints and EAMs were similar in pts with and without prior anti-TNF exposure (Table). By Wk4, CZP treatment was associated with rapid improvements in all measures of joint disease activity, including TJC, SJC and DAS28(CRP). Improvements in all outcomes continued through to Wk96 and were very similar in pts with and without prior anti-TNF exposure (Table). Similarly, improvements in nail psoriasis, enthesitis and dactylitis were seen to Wk96 of CZP treatment in PsA pts regardless of their prior anti-TNF exposure (Table). However, these analyses were limited by the low number of pts with prior antiTNF exposure. Conclusion: Improvements in joint outcome measures and EAMs of PsA were observed over 96 wks of CZP treatment. These improvements were seen across multiple joint outcome measures and in all EAMs assessed, including nail psoriasis, enthesitis and dactylitis. Similar improvements were observed in pts with and without prior anti-TNF exposure. References: 1. Mease P. Arthritis Rheum 2014;66(S10):S237–8 2. Khraishi M. Ann Rheum Dis 2015;74(S2):353–4 3. Mease P. Ann Rheum Dis 2014;73(1):48–55
Disclosure: D. D. Gladman, Abbott, Bristol Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, 5,Abbott, Bristol Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, 2; A. B. Gottlieb, Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, Pfizer, 2,AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celgene, Coronado, CSL Behring Biotherapies for Life, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, 5,UCB Pharma, Vertex, Xenoport, 5; B. Hoepken, UCB Pharma, 3; L. Peterson, UCB Pharma, 3; O. FitzGerald, Pfizer, Abbvie, Roche, MSD, BMS, 2,Pfizer, Abbvie, UCB Pharma, Roche, MSD, BMS, Eli Lilly, 9,Janssen, Abbvie, UCB Pharma, Roche, Cellgene, 9,Janssen, Pfizer, Abbvie, UCB Pharma, Cellgene, 9.
View Abstract and Citation Information Online - http://acrabstracts.org/abstract/long-term-improvements-with-certolizumab-pegolin-joints-and-extra-articular-manifestations-of-psoriatic-arthritis-in-patients-with-and-without-prior-anti-tnf-exposure
Abstract Number: 2836
Early Clinical Response Is a Better Predictor of Long-Term Remission Than Baseline Disease Characteristics Following Adalimumab Treatment in Peripheral Spondyloarthritis Filip van Den Bosch1, Philip J. Mease2, Joachim Sieper3, Dominique Baeten4, Nupun A. Varothai5, Aileen L. Pangan5 and In-Ho Song5, 1Ghent University Hospital, Ghent, Belgium, 2Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, 3Charité Universitätsmedizin Berlin, Berlin, Germany, 4Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, 5AbbVie Inc., North Chicago, IL First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster III: Therapy Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: ABILITY-2 has demonstrated the efficacy of adalimumab (ADA) vs. placebo (PBO) over 12 weeks (wk) in patients (pt) with peripheral spondyloarthritis (pSpA)1 and sustained response following up to 2 years (yr) of ADA. The purpose of this study is to determine predictors of long-term remission in pts with pSpA. Methods: In ABILITY-2 pts were randomized to receive ADA 40 mg every other wk or PBO during a 12-wk double-blind period, followed by an open-label period of up to 3 yrs of treatment. PSpARC1 remission was defined as SJC ≤1 plus 4/5 of the following: Physician's Global Assessment (PGA) of Disease Activity ≤20 mm (visual analog scale, VAS); PGA-pain ≤20 mm VAS, TJC ≤1, enthesitis count ≤1, dactylitis count ≤1. ASDAS inactive disease (ASDAS ID) was ASDAS score +100 0 -65 >+100 -35 -51 >+100
DAS28 BLDAS28 W12 SJC BLSJC W12 TJC BLTJC W12 5.0 2.4 5.1 3.5 4.3 5.9 5.8 4.5 5.9 4.5 4.1 4.3 4.5
2.7 2.3 4.2 1.0 3.5 5.5 3.6 1.5 2.8 4.2 3.8 2.6 4.8
9 6 5 2 5 5 3 1 18 2 9 19 9
2 4 3 1 8 4 4 0 0 2 20 9 4
9 4 22 3 7 16 25 1 18 10 1 5 18
0 4 4 1 11 19 0 0 0 12 8 15 57
Treatment Change after 12 weeks [y/n] n n y n y y n n n n y y n
Conclusion: Preliminary data of the first interims analysis of the XPLORE study illustrate high sensitivity in patients newly treated with Etanercept-therapy. Achievement of improvement of at least 45% in fluorescence intensity shows already after 4 weeks a high discriminative value for prediction of later clinical response at week 12. Only one patient was qualified as responder although he did not meet the criteria for response in fluorescence signalling. In this case, disease activity seems to be driven by other factors than inflammatory arthritis (only 1 SJC/TJC at baseline). Early change in fluorescence signalling seems to be a promising marker for prediction of clinical response in newly initiated biological treatment. Disclosure: M. Koehm, Pfizer Inc, 2,MSD; Pfizer, 5,Janssen Pharmaceutica Product, L.P., 8; T. Rossmanith, Pfizer Inc, 2; U. Henkemeier, None; P. Aries, Pfizer Inc, 8,Pfizer Inc, 2; R. Alten, Pfizer Inc, 5,Pfizer Inc, 2,Pfizer Inc, 8; H. E. Langer, Pfizer Inc, 2; H. Burkhardt, AbbVie Deutschland; Pfizer; BMS; UCB; Chugai, 5,Pfizer Inc, 2; F. Behrens, AbbVie Deutschland GmbH & Co KG; Chugai; Pfizer; Roche, 5,Pfizer Inc, 8. View Abstract and Citation Information Online - http://acrabstracts.org/abstract/non-response-to-antitnf-treatment-in-psoriaticarthritis-can-be-predicted-by-an-objective-automated-measurement-of-fluorescence-signal-intensities-in-fluorescence-optical-imagingtechnique-the-first
Abstract Number: 2856
Efficacy and Safety of Ustekinumab in Psoriatic Arthritis Patients with Spondylarthritis As Well As Peripheral Arthritis: Results from 2 Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study Arthur Kavanaugh1, Luis Puig2, Alice B. Gottlieb3, Christopher T. Ritchlin4, Yin You5, Shu Li5, Michael Song5, Bruce Randazzo5, Proton Rahman6 and Iain. B. McInnes7, 1University of California San Diego, La Jolla, CA, 2Universitat Autònoma de Barcelona, Barcelona, Spain, 3Tufts Medical Center, Boston, MA, 4Allergy, Immunology and Rheumatololgy Division, University of Rochester Medical Center, Rochester, NY, 5Janssen Research & Development, LLC, Spring House, PA, 6Rheumatology, Memorial University of Newfoundland, St Johns, NF, Canada, 7Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, United Kingdom First publication: September 29, 2015 SESSION INFORMATION Session Date: Tuesday, November 10, 2015 Session Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster III: Therapy Session Type: ACR Poster Session C Session Time: 9:00AM-11:00AM Background/Purpose: To evaluate ustekinumab(UST) in a subgroup of psoriatic arthritis (PsA) pts with physician diagnosed spondylarthritis, as well as peripheral arthritis, from the PSUMMIT 1 & 2 trials. Methods: Adult PsA pts with active disease were randomized to UST45mg, 90mg, or PBO at wks 0,4, and q12wks, thereafter. PBO-
pts crossed over to UST45mg at wks24 and 28 followed by q12wk dosing. At wk16, pts with