Abstracts of the 16th Asia Pacific League of Associations for Rheumatology Congress, 31 March-4 April 2014, Cebu City, Philippines.

International Journal of Rheumatic Diseases 2014; 17 (Suppl. 1): 1–133

PLENARY LECTURE ABSTRACTS PL1 – Plenary Lecture 1

APLAR-0536

ABC (antibodies, B cells, cytokines) in autoimmune diseases ¨ RNER T DO Department of Medicine, Rheumatology and Clinical Immunology, Charite - University Medicine, Berlin Given the genetic risk predisposition for SLE, systemic autoimmunity develops following environmental triggering and subsequent interplay of innate and adaptive immunity critically linked by antigen-presenting cells (APCs) resulting in the breakdown of tolerance, generation of autoantibodies and cytotoxic T cells. This apparently can lead to a positive forward loop which maintains autoimmunity between critical elements of innate and adaptive immunity. What determines which organs are involved remain poorly understood, although the initiating tissue appears to provide a decisive microenvironment. Understanding of these

processes is important to better understand various organ manifestations in SLE and to identify best treatment options. Tissue and organ autoimmunity is initially mainly driven by local dendritic cells and invading plasmacytoid dendritic cells leading to an autoimmune response that utilizes type I interferon and other cytokine networks. Subsequently, autoreactive T and B cells form germinal center-like structures likely involved in the formation of autoimmune memory and establishing immune effector functions, including autoreactive antibodies produced by plasma cells. A recent hypothesis has been put forward where a positive feed forward loop between innate and adaptive immunity may maintain autoimmunity in SLE in addition fueled by the lack of clearance of the autoantigens, including defects in apoptosis, increased netosis etc. The presentation will highlight a number of mechanisms behind immune dysregulation and pathways of systemic autoimmunity in systemic lupus erythematosus. A number of recent insights have been obtained within the last decade based on therapeutic interventions by clinical studies. These have provided lessons about the role of specific pathways, such as the involvement of BAFF/BLyS, IL-6, type I IFN as well as autoreactive T and B cells, including long-lived plasma cells residing in the bone marrow. Different immune pathways are likely driven by distinct dendritic cells in the target tissue that apparently direct heterogeneous immune activation pathways.

© 2014 The Authors International Journal of Rheumatic Diseases © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

PL2 – Plenary Lecture 2


Genomewide association studies in autoimmune diseases D KASTNER Division of Intramural Research, National Human Genome Research Institute, USA Abstract not available.

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APLAR-0532

The evolution of Lupus therapy RA LEVY Reumatologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Lupus flares’ control and survival rate has improved in the recent decades, but the damage index (SDI) continues to increase. The early cases of deaths in SLE are due to disease flare, or due to infection related to immunosuppression. Late deaths are more likely to be due to endstage renal disease, treatment complications (>50% of cardiovascular disease) and malignancies. A great amount of damage is due to the overuse of corticosteroids (CE), which are still


essential to control active disease. The recent SLICC classification is more sensitive than the ACR criteria. Identifying the markers of subsets and flares is important to plan and individualize treatment. Keeping in mind the prevention of damage, the aim of therapy is to control disease activity with the least dose and time necessary of CE, combined with hydroxycholoroquine and immunosuppessors as necessary, with the control of specific involvements (APS, cardiovascular and osteoporosis risk factors). Oral mycophenolate mofetil (MMF) for nephritis induction and IV cyclophosphamide are equally effective, while MMF is safer. For maintenance MMF seems to be better than azathioprine, while as second line the new emerging therapies are being used more frequently. Belimumab is approved worldwide, it was shown to control disease activity and prevent severe flares. Patients that are more likely to benefit from belimumab therapy are those with higher disease clinical and immunologic markers and that require more CE. In severe refractory presentations, off-label use of rituximab is increasingly reported. Other agents targeting the immune system are under investigation.

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APLAR-0509

The race to save the joint from end stage disease DJ HUNTER Rheumatology, University of Sydney, Sydney, NSW, Australia Osteoarthritis (OA) is at the forefront of an exploding epidemic of non-communicable chronic diseases. Beyond the pharmacological and surgical advances, there are

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population-based interventions that are already proven effective for preventing the development of OA. These measures include lifestyle management, maintaining a healthy weight, remaining active, and avoiding joint injury. Modern health care systems are typically reactive and focused upon acute care whereas the management of OA is ideally efficient, coordinated and patient centred to support integration of evidence into practice. Inflation in the cost of health care is driving changes to health systems that will not only enhance the organizational costs of OA delivery but also health outcomes. Clinicians should pay greater heed to the benefits of weight management and exercise in the management of disease, which we are not currently doing very well. Looking into the future researchers are making tremendous strides in both pain relief and structural modification. On the structural modification side, look for agents that target cartilage as well as bone.




APLAR-0560

The Asian RA treatment guidelines project CS LAU Department of Medicine, University of Hong Kong, Hong Kong, China Much progress has been made in the drug treatment of rheumatoid arthritis (RA) in the past two decades. Judicious use of symptomatic agents and conventional and novel disease modifying anti-rheumatic drugs (DMARDs) lessens pain and discomfort, enhances the chance of disease remission and minimizes the risk of unwanted side-effects. Globally, multiple national


and regional treatment recommendations and guidelines have been developed to aid practicing clinicians and decision makers to improve health care delivery to persons with RA. However, none of these existing recommendations / guidelines take into account the practice setting of many Asia Pacific countries. Recently, APLAR assembled a working group clinicians, researchers and patient consumers to develop the region’s first treatment recommendation for patients with RA. The Group first defined the objectives and scope of the intended recommendations. Clinical questions were raised pertaining to the overall treatment goals and strategies, drug treatment for symptom control, indications for conventional and biologic DMARDs, safety monitoring and management of treatment adverse reactions, particularly infective complications. The first draft is being developed and the Group wishes to use this opportunity to present this to a wider and larger audience of practitioners who manage patients with RA for their opinion and feedback.

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APLAR-0556

Future directions in the management of autoimmune diseases S SOCKALINGAM Department of Medicine, University Malaya, Kuala Lumpur, Malaysia Our knowledge of the pathogenesis and mechanism of autoimmune diseases have increased tremendously in recent years. The advent of biologic therapy, specifically monoclonal antibodies in the management of diseases such as rheumatoid arthritis and more recently systemic lupus erythematosus are examples of the development of novel therapies resulting from knowledge gained through this research. The identification of cytokines, key receptors and intracellular signalling mediators in the pathogenesis of disease are the primary drivers in research. In addition to the control of disease activity these therapies have to be as minimally immunosuppressive as possible to avoid susceptibility to infections. Therapy also must address disease induced damage of target organ, fatigue, cardiovascular and musculoskeletal

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effects. However, selecting patients most suitable for a new therapeutic agent is rapidly becoming important, thus new predictive biomarkers are required in tandem with the development of novel therapies. Monoclonal antibodies to CD20 and CD52 are probably useful across a range of disorders and will likely remain an important choice of therapy. Helper T cell subsets may have a prominent role in determining the phenotype of the autoimmune disease, thereby potentially determining the direction of management. Another development is the identification of disorders related to IgG4. A wide range of systemic effect of this group of diseases are noted, such as lymphadenopathy, interstitial pneumonitis and membranous glomerulonephritis. Collectively known as IgG4 related disorders (IgG4-RD) they are thought to be due to lymphoplasmacytic tissue infiltration with a predominance of IgG4 plasma cells and T lymphocytes. Another entity that is recognizable from the research into mediators of autoimmune diseases is the macrophage activation syndrome (MAS) that has been noted in many autoim~ disease and polyarteritis mune diseases such lupus, rheumatoid arthritis, adult onset StillOs nodosa. Activated macrophages secrete excessive amount of cytokine and Toll Like receptor 9 is also activated as similarly seen in lupus. These are examples of mechanisms that are shared by various autoimmune diseases, and perhaps we will be able to uncover more such groups that will influence management of autoimmune diseases in the future.


CS1A -Concurrent Symposium 1A: Systemic Lupus Erythematosus

SYMPOSIA ABSTRACTS CS1A – Concurrent Symposium 1A: Systemic Lupus Erythematosus

APLAR-0508

The future of biologics in SLE R CERVERA

encephalomyelitis. Thus, targeting DCs may be feasible therapeutic option in the treatment of autoimmune diseases. Indeed, the mechanisms of action of hydroxychloroquine, an antimalarial that have been used for decades in the treatment of SLE and rheumatoid arthritis, have recently been demonstrated to reduce type I interferon production by plasmacytoid DCs via blockade of intracellular toll like receptors.

Autoimmune Diseases, Hospital Clınic, Barcelona, Spain Prognosis in systemic lupus erythematosus (SLE) has improved markedly in the last 50 years. From a mortality rate higher than 50% after 5 years of SLE diagnosis in the 60«s to a more than 90% survival after 10 years in the more recent prospective studies. The challenges for the years to come are to improve the quality of life of these patients and to reduce even more the mortality. In order to achieve these objectives, three main goals should be addressed: (1) To improve the use of some drugs already available; (2) to introduce in the clinical practice some drugs that are currently in phase I-III trials; and (3) to increase the basic research in order to discover targets for new selective immunomodulators. This presentation overviews these three goals in the therapeutical perspectives of SLE, with special emphasis on the new biological agents, such as anti-BlyS, anti-CD20, anti-CD22 and anti-CD40L monoclonal antibodies, LJP 394 and LJP 1082 and CTLA4Ig, among others.

APLAR-0547

Dendritic cells: role and therapeutic implications in autoimmunity MY MOK Division of Rheumatology & Clincial Immunology, The University of Hong Kong, Hong Kong, Hong Kong China Dendritic cells (DCs) are professional antigen presenting cells (APCs) and are key immune cells that bridge innate and adaptive immunity. DCs express toll-like receptors facilitating recognition of microbial antigens. Activated DCs prime and drive differentiation of na•ve T cells to different effector cells. DCs also play an important role in the maintenance of peripheral tolerance. Dysregulated DC maturation and function have been shown to contribute to autoimmunity. Plasmacytoid DCs as potent secretors of type I interferon and myeloid DCs as professional APCs, are involved in disease pathogenesis in autoimmune diseases such as systemic lupus erythematosus (SLE), type 1 diabetes and experimental autoimmune


APLAR-0551

Lupus nephritis treatment beyond the NIH protocol B HAHN, J GROSSMAN, M MCMAHON, J GROSSMAN Rheumatology, University of California, Los Angeles, CA, USA Lupus Nephritis (LN) Treatment Beyond the NIH Protocol, Bevra Hahn, MD, Professor UCLA, Los Angeles, CA, USA Current EULAR and ACR guidelines for treatment of LN include INDUCTION of improvement, MAINTENANCE and PREVENTION of damage. Recommended INDUCTION for Class III, IV, V combines high dose glucocorticoids (GC) with immunosuppressives (IS), either mycophenolate mofetil (MMF) or cyclophosphamide (CYT) for 6 months; GC doses should be tapered during that time. After 9 weeks, 25% reduction in proteinuria and increased serum complement predict good response. At 6 months response rate is 50% (20% complete responses) with increase at 12 months to 75%. Low-dose CYT (500 mg i.v. every 2 weeks 9 6, followed by MMF or AZ) may be as effective as high dose (750 mg/M2 i.v. monthly 9 6) for INDUCTION in some races. In responders, either MMF or AZ for 3 years may be used for MAINTENANCE. PREVENTION included treating all patients with hydroxychloroquine (HCQ) plus angiotensin inhibitors or angiotensin receptor blockers. In non-responders, induction therapy should be change either to teh IS that was not chosen initially (ACR) ot to rituximab (EULAR). Azathioprine is acceptrable for inducdtion or mainenance, higher flare rates occur over the long term. Since 25% do not respond, and renal scarring with ESRD occurs in 15%, new approaches are under study. They include targeting B or T cells (belimumab, epratuzumab, abatacept), inhibition of C5a (eclizumab), inhibion of macrophages (laquinimod), and inhibition of TLR activation, T and B cell activation pathways (TOR, JAK/TYK/STAT), proteasomes and PDG4. We will review data suggesting that pulse glucocorticoids plus rituximab plus daily MMF, without additional daily GC, may be sufficient treatment for some cases of LN, thus reducing steroid morbidity.

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CS1B – Concurrent Symposium 1B: Connective Tissue Diseases 1

CS1B – Concurrent Symposium 1B: Connective Tissue Diseases 1

APLAR-0541

Targeting microRNAs in lupus: microplayers in the big game N SHEN Ren Ji Hospital Shanghai JiaoTong University School of Medicine, Shanghai Institute of Rheumatology, Shanghai, China It has been well established that microRNAs maintain normal physiology and modulating contribute to disease pathophysiology through transcription and epigenetic pathways. Targeting miRNA has been considered as a promising therapeutic approach for the diseases of immunological origin. We have shown that miRNAs singly or synergistically activate abnormal immune and inflammatory pathways, leading to pathological lupus autoimmune responses including hyperactivation of type I IFN pathway, inflammatory chemokine RANTES overproduction, IL-2 secretion defect, T cell DNA hypomethylation and local tissue inflammation. More importantly, Inhibiting or reducing these abnormal miRNAs restores normal immune function in in vitro cell culture. We thus hypothesize that in vivo manipulation of these miRNAs expression could regulate major inflammatory signaling pathways linked to lupus tissue damage and the approach to correct these dysregulated miRNAs should reverse lupus major phenotypes. Recently we have been evaluating the capacity of selective miRNA inhibition to cure lupus in murine models (spontaneous lupus prone B6. Sle123 mouse and pristane-induced lupus), as preparatory experiments before advocating human trials using this approach. We have applied gene knockout, transgenic and bone marrow chimeric mice, as well as chemically synthesized miRNA mimics and inhibitors, to study the role of miRNAs in inducing lupus-related pathological tissue damage. We also determined the potential for reversing disease and evaluate efficacy, while also elucidating the miRNA-related molecular mechanisms of lupus pathogenesis. We believe the results of these experiments would prepare our community of lupus investigators and pharmaceutical scientists to exploit this exciting new technology toward ending the suffering caused by lupus.

among the autoimmune diseases. Treatment for SSc has so far demonstrated limited efficacy. To date, clinical trials of immunomodulating drugs have been discouraging, in part due to an inadequate understanding of the pathogenesis of this complex disease. Another reason is that patients recruited into the trials were heterogenous in terms of disease stage and disease subtype. This talk will provide an up-to-date review of the pathogenesis of SSc, with a particular focus on relating the underlying pathogenesis to both current and novel treatments in the pipeline.

APLAR-0513

Dealing with the scleroderma complications – ulcers and calcinosis V HSU Department of Medicine, Rutgers-RWJ Medical School, New Brunswick, Canada 1 2 3 4 5 6 7

2013 ACR-EULAR scleroderma classification (nine points). Pathophysiology of scleroderma: defect in angiogenesis. Digital ulcers and management. Raynaud management. Calcinosis- what is it? Complications of calcinosis. Management of calcinosis.

APLAR-0542

Are we cracking the nut of scleroderma pathogenesis and treatment? AHL LOW Singapore General Hospital, Rheumatology and Immunology, Singapore, Singapore Systemic sclerosis (SSc) is characterised by immune dysregulation, fibrosis and vasculopathy, resulting in skin fibrosis and internal organ complications. SSc has one of the worst prognoses

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CS1C – Concurrent Symposium 1C: Pediatric Rheumatology Symposium

CS1C – Concurrent Symposium 1C: Pediatric Rheumatology Symposium

APLAR-0530

Recent evidence for the use of biologics in pediatric rheumatic diseases

2014 year in review in Pediatric Rheumatology

Y ITOH

T ARKACHAISRI

Department of Pediatrics, Nippon Medical School, Tokyo, Japan

Rheumatology and Immunology, KK Women’s and Children’s Hospital and DukeNUS Graduate Medical School, Singapore, Singapore Despite a newest subspecialty in Pediatrics, pediatric rheumatology knowledge has continued to grow as we see and evaluate our patients and their therapy and outcomes. Many progresses in the field were witnessed both regionally and internationally. The session will update our current information on burden of pediatric rheumatic diseases in Asia-Pacific region based on the AsPREN study. Similarities and differences in disease phenotypes were evidenced. Prominent literatures published in 2013 which posed impact on our practice will be reviewed and discussed.

Abstract not available.

Epidemiology of infectious arthritis in pediatric patients L DANS Department of Pediatrics, University of the Philippines, Manila, Philippines Abstract not available.


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CS2A – Concurrent Symposium 2A: Connective Tissue Diseases 2

CS2A – Concurrent Symposium 2A: Connective Tissue Diseases 2

APLAR-0521

Triggers and mechanisms in the idiopathic inflammatory myopathies (IIM) SA HAQ Department of Rheumatology, BSM Medical University, Dhaka, Bangladesh The pathogenesis of idiopathic inflammatory myopathies (IIM) involves complex genetic and immune mechanisms. Current state of knowledge hint at the roles of genes, adaptive and innate immunity and environmental triggers. Genetic studies confirm the importance of major histocompatibility complex (MHC) and suggest genetic overlap with other autoimmune diseases. STAT4 and HLA-DRB1 have been identified as risk loci for polymyositis (PM)/dermatomyositis (DM) and anti-MDA5 associated amyopathic DM respectively. Three non-MHC genes have been associated with DM: PLCL1, BLK and CCL21. Several myositis-specific (MSAs) and myositis-assiciated antibodies have been identified in the sera of IIM patients. MSAs include anti-aminoacyl-tRNA synthetase, anti-Mi2, anti-TIF-1c, anti-HMGCR, antiMDA5, anti-SRP and anti-SUMO-1. Distinct clinical phenotypes associated with individual MSAs may permit an autoantibody-based reclassification of IIM. In PM and sporadic inclusion body myositis, MHC class I expressing muscles are injured by auto-invasive CD8+ T cells that act in concert with dendritic cells and macrophages found in the endomyseal area. In DM, infiltration B lymphocytes, CD 4+ T cells and macrophages are found in perimyseal areas and around small blood vessels. Other incriminated cells include CD28null T cells, Th 17 T cells and B cells. Expression of type-1- interferon (IFN)-induced genes and their protein products are upregulated in blood and muscle tissue in DM patients indicating a key role of type 1 IFN. Other cytokines/ chemokines of importance include IL17, BAFF, IL1, IL6, IL15, IL18, HMGB1 and LTB4. Evidence for gene-environment interaction have been found between HLA-DRB1*03 and smoking, and HLA-DRB1*11:1 and statins. Viruses and ultraviolet light are reported to be other triggers. IIM appears to result from environmental stimuli in genetically predisposed individuals. It appears that the coming years will witness a greater success in the treatment of IIM stemming from a clearer understanding of pathogenesis and a better classification system.

APLAR-0528

leading cause of arterial and venous thrombosis, recurrent fetal loss and other obstetric and clinical complications that are not included in the classification criteria. Some features can act as prognostic markers and may require a specific management. Diagnosing APS is challenging, aPL antibodies may be found in asymptomatic patients and in some predict events. Conversely, patients may have the classical features, yet no classical/ criteria laboratory tests (seronegative APS?!). For APS patients with previous venous thrombosis, AVK treatment targeting an INR of 2.5 is recommended, while for those with arterial events the target is 3.5. It is advised to actively control hypertension and hyperlipidemia, as well as other classical risk factors for thrombosis. In high-risk and invasive situations, AVK is replaced by short-term subcutaneous anticoagulation with low-molecular weight heparin (LMWH). Also, when pregnancy is detected in women with thrombotic APS, AVK is switched to full dose LMWH combined with low-dose aspirin. This treatment has improved life-birth rates, but the frequency of gestational complications remains high. Long-term treatment with AVK is troublesome, as it requires regular monitoring and rigorous compliance to medication and dietary habits. The new generation of oral anticoagulants is still being studied for APS, and there is still no data to support their use in APS patients. Other forms of anticoagulation, and hydroxychloroquine, statins, B-cell inhibitors and peptides are being studied for APS.

APLAR-0549

Making sense of SLE disease activity measures M NIKPOUR Rheumatology at St. Vincent’s Hospital, The University of Melbourne, Melbourne, Vic., Australia SLE is characterized by a relapsing-remitting course. Quantifying disease activity in each of the organ systems involved is a key driver of treatment decisions, and in a clinical care setting, is ~ judgment. However, standardized measurement of disoften based on the expert physicianOs ease activity in SLE, using validated instruments, is pivotal in both observational and interventional studies, in order to elucidate the determinants of the course of disease, and the efficacy of novel therapies. Now, more than ever, measurement of treatment response in SLE is crucial in clinical trials of numerous novel targeted therapies. This presentation will provide an overview of the characteristics of the most commonly used measures of disease activity in SLE, and ^ ~ persistently active disease, high and low disease explore related concepts of disease Oflare O, activity states, and clinically meaningful change in disease activity.

Updates in antiphospholipid antibody syndrome RA LEVY Reumatologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Since the identification of the antiphospholipid syndrome (APS/Hughes’s syndrome) a lot has been learned, with improvements in classification methods and outcomes. APS is a

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CS2B – Concurrent Symposium 2B: Osteoporosis

CS2B – Concurrent Symposium 2B: Osteoporosis

APLAR-0512

Bone anabolic therapy: the new frontier D KENDLER Department of Medicine, University of British Columbia, Vancouver, BC, Canada Most therapies currently approved for the management of osteoporosis inhibit osteoclastmediated bone resorption and reduce bone remodeling. Teriparatide [recombinant human PTH (1*34)] is the only bone anabolic therapy approved for the treatment of osteoporosis. Other anabolic therapies are in clinical trials now (few data are currently available). With their approval, our approach to treating severe osteoporosis will likely change. Teriparatide improves bone strength by building new bone tissue thereby improving the architecture of bone. Significant reductions in both vertebral and non-vertebral fractures have been demonstrated in multiple clinical trials of teriparatide. Head-to-head trials against alendronate have demonstrated superior Bone Mineral Density effects, with opposite effects on bone turnover markers consistent with its different mechanism of action. More advanced imaging techniques support data from bone biopsy studies regarding the anabolic properties of teriparatide. Moreover, Finite Element Analysis techniques confirm improvement in computer modelling bone strength in patients treated with teriparatide compared with bisphosphonate control. Although prior therapy with bisphosphonates may slightly blunt or delay the onset of the anabolic effect of teriparatide, the effects are still clinically significant. Concurrent PTH and bisphosphonate gives little advantage over monotherapy with PTH. There are limited data suggesting synergy in BMD effects for patients treated with combination teriparatide and denosumab. Subsequent therapy with antiresorptives such as bisphosphonate or raloxifene will consolidate the beneficial effects upon the skeleton after PTH is discontinued. Bone anabolic therapy with teriparatide, applied to appropriate patients at high risk of fracture, can greatly extend our ability to protect patients from osteoporotic fractures.

APLAR-0519

Long term treatment of osteoporosis: risks and benefits P CAMACHO Endocrinology and Metabolism, Loyola University Medical Center, Maywood, USA Drugs that are used to treat osteoporosis have proven efficacy and render significant fracture risk reduction. The most commonly used drugs are bisphosphonates, which have been around for a few decades. Long term safety of these agents, however, has become a concern with the emergence of rare adverse events, specifically atypical fractures of the femur and osteonecrosis


of the jaw. In 2010, The American Association of Clinical Endocrinologists (AACE) Postmenopausal Osteoporosis Guidelines recommended a drug holiday after 4–5 years of therapy for patients with moderate risk for fractures and after 10 years for those who are high risk. This talk will include a discussion of these recommendations as well as the American Society of Bone and Mineral Research (ASBMR) statements defining atypical fractures and ONJ. Several studies that have looked at the incidence of atypical fractures and ONJ will also be reviewed as well as studies that have compared continuation of therapy versus drug holidays. Osteoporosis patients who are untreated have significant fracture risk, and given the rarity of these long term issues, the benefit of using these agents far outweighs their risk. It is important however, that clinicians are aware of current practice recommendations of initiating bisphosphonate drug holidays, to know what needs to be monitored during this period and when to reinstitute therapy.

APLAR-0525

The role of Vitamin D and calcium in osteoporosis treatment N ISLAM Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh To prevent compensatory rise in parathyroid hormone and excessive bone resorption, positive calcium balance and adequate vitamin D is essential. Inadequate serum 25-hydroxyvitamin D (25OHD) concentrations are associated with muscle weakness, decreased physical performance, and increased propensity in falls and fractures. Although not all, many observational studies have shown higher risk of hip fracture with lower serum concentrations of 25OHD. Not only hip fracture, low serum concentrations of vitamin D found to be associated with a higher risk of other major osteoporotic fractures. Both observational and randomized, placebo-controlled trials observed benefit of calcium and vitamin D supplementation in patients with osteoporosis on preventing bone loss. Regarding reduction of fracture risk, data from randomized trials are more variable. Some trials have reported a reduction in fracture but large trials have not shown any reduction except in compliant subjects group. Randomized trials of calcium only or vitamin D only have shown beneficial for bone density but not for fracture risk reduction. The daily intake of 1000 mg of elemental calcium and actual intake of 800 IU vitamin D can result in positive calcium balance and reduce risk of fracture. Calcium carbonate with meals is adequate and inexpensive. For proton pump inhibitors users, better option is calcium citrate. The total intake of calcium (diet plus supplements) should not exceed 2000 mg/day and safe upper limit for vitamin D is 4000 IU. Compliance to calcium and vitamin D therapy is paramount for effective prevention of osteoporosis and fracture risk reduction.

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CS2C – Concurrent Symposium 2C: Infections in Rheumatology

CS2C – Concurrent Symposium 2C: Infections in Rheumatology

APLAR-0522

Infections and arthritis: history remade P PISPATI Rheumatology - Director, Jaslok & Saifee Hospitals, Mumbai, India ~ cockOs ~ crow with Immunology and Rheumatology have evolved in tandem. Edward JennerOs ~ first microscope, KochOs ~ and MetchnikoffOs ~ actualization smallpox vaccine, LeeuwenhoekOs of germ-humoral theory of diseases led to demonstration of antibodies and later, autoantibodies eg. rheumatoid factor, antinuclear antibodies, antiphospholipid antibodies. Thanks to derivative cytokines, we now have monoclonal antibodies the beginning of targeted therapies to tame collagen vascular diseases all autoimmune. Now the question: are these infectious in origin? e.g. rheumatic fever, lupus, antiphospholipid syndrome; more to follow with prospective vaccines? Free Arthritis camps that we conducted in India (n = 6400 patients) revealed that 14% of all RA patients and 17% of all SLE patients were harbouring active tuberculosis (TB). Now the question: is lurking TB actually inducing SLE? That HLA- B27 is strongly associated with ankylosing spondylitis triggered by gut infections is well documented. In India patients of juvenile spondyloarthropathy TB was diagnosed in 14.3% with 60% HLA B27 positivity. Similar HLAB27 with TB association is reported elsewhere; also with Plasmodium falciparum in India. Understanding living hundred trillion strong microbiome inside homo sapiens vis-ˆ-vis autoimmune disorders with genetic predisposition can be the basis of quicker bed-side diagnostics tests, novel probiotics and preferential biotechnology molecules on the anvil to combat infections and autoimmune disorders; rendering medical practice purpose specific, predictive, preventive and participative. The harmonious new science of Rheumatology and Immunology merits the new term Rheu history in the making. manology E

APLAR-0562

Infection and rheumatic diseases: a regional perspective E VISTA Rheumatology Center, St. Luke’s Medical Center and College of Medicine, Taguig, Philippines Infections act as major environmental triggers inducing, promoting and/or complicating systemic autoimmune disorders. Early environmental exposures may influence autoimmunity development in select individuals. Several critical pathologic mechanisms may influence

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interactions between infection and autoimmunity. Molecular mimicry, epitope spreading, exaggerated local activation of antigen-presenting cells, and priming of large numbers of T cells with broad specificities all may have important roles in lupus autoimmunity. Polyclonal activation of infected B cells resulting in B-cell proliferation, enhanced antibody production, and generation of circulating immune complexes, as well as bystander T cell activation, may promote overt disease. The interplay of infections and select genetic polymorphisms are only beginning to be evaluated. The exotic pathogens seen among patients and vary among regions in the Asia Pacific parallel the variety of clinical manifestations to which they contribute to the disease process. Exposure to the Chikungunya virus promoting a protracted course of arthritis is one example.

APLAR-0540

Infectious agents, arthritis and autoimmunity A LATEEF Department of Medicine, National University of Singapore, Singapore, Singapore The autoimmune disorders are a diverse group of conditions characterized by loss of Oself-tol with abnormal immune reactivity in association with auto-reactive B and T cell eranceO responses. Multiple factors are believed to contribute to the development of autoimmunity, including genetic predisposition, hormonal milieu, and environmental influences. The most important environmental factor with a potential to trigger autoimmunity are the infectious agents like bacteria, viruses and other pathogens. Many theories have been proposed to explain the possible mechanisms linking infections to autoimmunity. These include release of hidden antigens, epitope spread, anti-idiotypes, molecular mimicry, the adjuvant effect, antigenic complementarity or direct consequence of the immune response by microbes. In addition, interplay of microbial and host factors have also been shown to influence the immune responses. It is highly likely that more than one mechanism is required for the development of a clinical autoimmune disease. The pivotal role of infection in the induction of autoimmune disorders has been supported by several lines of evidence, such as epidemiological data, serological correlation, animal studies, and in some cases, the isolation of infectious agents or their genomic foot print from affected tissues of patients. Some examples of autoimmune diseases with accumulating evidence of infectious links include rheumatoid arthritis, sero-negative spondyloarthropathy, and connective tissue diseases such as systemic lupus erythematosus and vasculitis. The pathogenetic mechanisms linking periodontal infections to rheumatoid arthritis provides an excellent example of interaction of multiple host and microbial factors leading to the development of autoimmunity. Similarly, interactions between HLA B27 subtypes and bacterial antigens predispose certain individuals to seronegative spondyloartropathy, again highlighting the complex interactions between genetics and environment.


CS3A -Concurrent Symposium 3A: Osteoarthritis

CS3A – Concurrent Symposium 3A: Osteoarthritis

Defining pathogenesis of OA

APLAR-0535

M ISHIMORI

Lessons from a dedicated OA service

Department of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, USA

K LIM1, A LEUNG1, C PAGE2

Abstract not available.

APLAR-0552

Epidemiology of OA in Asia J THUMBOO Department of Rheumatology and Immunology, Singapore General Hospital and DukeNUS Graduate Medical School, Singapore, Singapore Osteoarthritis (OA) is a prevalent problem in Asia, as has been demonstrated in COPCORD studies in various Asian countries. Ethnic differences have been observed: for example Chinese in Beijing have less hip OA, more lateral compartment involvement in knee OA and moe valgus deformities than subjects in the Framingham study. The burden of OA is growing with the aging population in Asia. For example, OA was among the 10 most common contributions to Disability Adjusted Life Years in Singapore in subjects ≥35 years of age. Given the growing burden of disease, coordinated efforts are needed to address the burden of OA, ideally at a community and primary care level.


1 Rheumatology, Western Hospital, Melbourne, Vic., Australia, 2Physiotherapy, St Vincents Hospital, Melbourne, Vic., Australia

In 2007 following a Victorian Department of Health initiative we piloted an OA service whereby patients who were listed to see the orthopaedic surgeon was instead triaged to visit an OA clinic comprising rheumatology, physiotherapy, and other support services. This service has become a core activity of the Victorian DHS with some variations. I will discuss our experience and findings for the cohort over the past 7 years. In summary, we reduced the waiting times to be seen, a significant proportion of patients did not require surgery or to see a surgeon. We were able to conservatively manage the majority of patients with hip and knee patients. What was clear was that hip and knee disease behaved differently in response to conservative care. We were better at managing knee OA than hip OA non surgically. Delaying surgery did not appear to affect outcomes adversely. Arthroscopy rates dropped significantly. We believe satisfaction rates were high amongst patients, staff and our orthopaedic colleagues. I will also discuss certain criteria which are essential to the success of such a model. More work however has to be done to measure the economic and health impact on patients of such a model of care. model versus the Otraditional O

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CS3B – Concurrent Symposium 3B: Basic Science of Joints

CS3B – Concurrent Symposium 3B: Basic Science of Joints

APLAR-0564

Strategy for osteoarthritis via stress response of chondrocyte K TAKAHASHI1, S TAKAI1, H NAKAMURA2, S HASHIMOTO3 1

Department of Orthopaedic Surgery, Nippon Medical School, Tokyo, Japan,, Department of Rheumatology, Nippon Medical School, Tokyo, Japan, 3MinamiShinjyuku Orthopaedic Rehabilitation Clinic 2

Osteoarthritis (OA) is based on the gradual degeneration of the articular cartilage and the number of patients with symptoms has been increasing in this aging society. Since medical therapies such as the oral administration of non-steroidal anti-inflammatory drugs cannot change the natural course of OA nor greatly suppress the progression of OA, it is necessary to establish a treatment strategy from various aspects, such as developing effective physical therapy and combining such therapy with others. On the other hand, hyperthermia is commonly used for OA in clinical setting, while clinical evidence of the efficacy has not yet become adequate. In addition, the application of a modality that can control the temperature of the articular cartilage and the subchondral bone that are present in deep parts of the joint structure has not been established. We previously demonstrated that the expression of proteoglycan and type II collagen in the articular cartilage significantly increased at a level in which the temperature inside the joint increased to approximately 40°C. Moreover, heat shock protein 70 (HSP 70) accumulated in chondrocyte when the articular cartilage was heated provides effects to inhibit apoptosis of chondrocytes and to accelerate the proteoglycan metabolism. We will discuss some studies about the effect of heat stress on articular cartilage to realize the mechanism of hyperthermia on OA. In addition, a radiofrequency hyperthermia on knee OA, which can safely increase the temperature inside the knee joint and provide a remarkable pain relief effect, will be introduced.

APLAR-0510

Inflammation in osteoarthritis D HUNTER Rheumatology, University of Sydney, Sydney, NSW, Australia Osteoarthritis (OA) has long been considered a ‘wear and tear’ disease leading to loss of cartilage and boney response. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an ‘inflammatory’ theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. The synovial reaction in OA includes synovial hyperplasia, fibrosis, thickening of synovial capsule, activated synoviocytes and in some cases lymphocytic infiltrate (B- and T-cells as well

14

as plasma cells). The site of infiltration of the synovium is of obvious relevance as one of the most densely innervated structures of the joint is the white adipose tissue of the fat pad which also shows evidence of inflammation and can act as a rich source of inflammatory adipokines. Synovial causes of pain include irritation of sensory nerve endings within the synovium from osteophytes and synovial inflammation that is due, at least in part, to the release of prostaglandins, leukotrienes, proteinases, neuropeptides and cytokines. Synovitis and effusion are frequently present in OA and relate to pain severity, pain change and structural progression. Subchondral bone also has a substantial role in the OA process and is a source of inflammatory mediators implicated in the OA pain process and in the destruction of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease of the whole joint with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA.

APLAR-0550

Hand osteoarthritis K LEUNG Department of Rheumatology & Immunology, Singapore General Hospital, Singapore, Singapore Hand osteoarthritis (HOA) affects more than half of the elderly population. Among HOA patients, 30% are symptomatic; incurring pain, disability and impaired health related quality of life (HRQoL). Preliminary studies suggest the burden of HOA is similar to rheumatoid arthritis (RA), but the true impact of HOA to disability and HRQoL has not been well studied. The consensus work of the Outcome Measures in Rheumatology Clinical Trials Group (OMERACT) recommended pain, physical function and patient global assessment as key outcomes in knee, hip and hand OA in clinical trials. Although pain and physical function are of major importance for assessing health, they do not adequately reflect HRQL in all dimensions. The Osteoarthritis Research Society International (OARSI) recommended measuring HRQL in HOA. However, it has not been clear how HRQoL in these patients should be measured. Generic HRQoL instruments have been used in HOA, and no disease specific HRQoL has been developed. Aesthetic concern was never studied, although this is a major complaint in daily practice. There are some existing instruments used in the literature for measurement of physical function in HOA, these instruments were developed from a list of concepts selected by professionals, which disagrees with the FDA recommendation that patient inputs should be elicited. A European multi-national qualitative study revealed that a considerable number of concepts in physical function that are important to patients with HOA were not addressed with commonly used instruments. None of these instruments address cultural and ethnic differences in various populations. We present preliminary data on a qualitative study on HRQoL in subjects with HOA in the Asian context.


CS3C – Concurrent Symposium 3C: Diagnostics and imaging in Rheumatology

CS3C – Concurrent Symposium 3C: Diagnostics and imaging in Rheumatology

APLAR-0517

Ultrasound in Rheumatology GAW BRUYN Rheumatology, MC Groep Hospitals, Lelystad, Netherlands Along with an ever increasing amount of potent treatments enabling swift and effective suppression of inflammation in rheumatoid arthritis and other inflammatory arthropathies, there is a growing need for an accurate method of detection of active disease and monitoring response to therapy. Musculoskeletal ultrasound (MSKUS) is an extremely useful and versatile imaging technique for visualizing both joints and bones and soft tissues, such as tendons, nerves andligaments. Ultrasound has the advantage of of being readily available and inexpensive; at the same time, it has the image of being examiner-dependent. Meanwhile, with the advent of modern high frequency probes, mastering MSKUS had come within reach of every clinical rheumatologist. Nowadays, MSKUS has come of age and has made inroads within the majority of hospitals where rheumatologists are practicing. It can be used to establish the diagnosis, dissect the differential diagnsos and guide aspirations and steroid injections. Moreover, an increasing number of rheumatogists conduct color Doppler studies to visualize not only inflamed tissues, but also to examine inflamed vesseld like in temporal arteritis. It can be expected that the range of indications may expand, notably including various vessel pathology, in the near future. The various features of MSKUS will be addressed in this lecture.

US is able to visualise almost all of the structures involved in the rheumatic diseases and, in the case of synovitis, US has a key role in the depiction of inflammation and also structural damages. Almost all of the joints can be visualised very clearly using B mode US. In synovitis, when using grey-scale technique, we can have information about inflammation by the presence of a joint space widening (the most characteristic US feature of joint inflammation); US permits an accurate distinction between joint effusion and synovial proliferation (characterised by clusters of soft echoes, with a bushy or villous appearance, and/or homogeneous synovial thickening). With power Doppler sonography, B-mode image information is enhanced by the depiction of the vascularity of soft tissue The Doppler technique (mainly power Doppler -PD- when dealing with synovitis), has recently been shown to be an efficient tool for monitoring disease activity and progression in many different diseases such as: rheumatoid arthritis, spondyloarthritis, crystal-related arthropathy, and osteoarthritis. PD signal has proved to be a simple and promising tool for short-term monitoring of synovial vascularity changes induced by steroids or biological agents in RA patients.

APLAR-0518

Sonography in vasculitis and other pathologies WA SCHMIDT Medical Center for Rheumatology Berlin Buch, Immanuel Krankenhaus Berlin, Berlin, Germany

APLAR-0523

B mode and doppler studies in inflammatory synovitis A DELLE SEDIE Rheumatology Unit, University of Pisa, Pisa, Italy In recent years, many advances have been made in the field of musculoskeletal ultrasonography (US), allowing it to become a very powerful tool in rheumatological clinical practice. Recent advances in US technology have resulted in dramatic improvements in quality and resolution of the imagery. High frequency transducers provide good image resolution and allow the depiction of details of 1 autoantibody. 86% patients with anti-Mi2 antibodies had dermatomyositis phenotype (P = 0.015). Patients with Antisynthetase antibodies were more likely to have ILD (P < 0.0001%), fever (P = 0.04), weight loss (P = 0.02), mechanics hands (P = 0.001) and arthritis (P = 0.08). Mi2 positive patient were more likely to have pharyngeal weakness (P = 0.01) and less likely to have ILD (P = 0.002) and arthritis (P = 0.05). Four out of five patients with anti-SRP antibody had refractory myositis. Conclusions: Our cohort had higher prevalence of anti-Mi2 antibodies, which can be attributed to ethnic variations. Anti-Mi2 positive patients have higher risk of developing pharyngeal weakness and lesser risk of having ILD and arthritis. Antisynthetase positive patients have higher risk of developing ILD, mechanics hand, fever and weight loss.


FP1A -Free Paper 1A: Connective Tissue Diseases

APLAR-0255

Outcomes of pregnancy in subjects exposed to certolizumab pegol M DE LONGUEVILLE6, MEB CLOWSE1, DC WOLF2, F FORGER3, C STACH4, G KOSUTIC5, S WILLIAMS5, I TERPSTRA6, U MAHADEVAN7 1

Medicine-Rheumatology and Immunology, Duke University Medical Center, Durham, USA, 2Atlanta Gastroenterology Association, Atlanta, USA, 3Department of Rheumatology and Clinical Immunology and Allergology, University of Bern, Bern, Switzerland, 4UCB Pharma, Monheim, Germany, 5UCB Pharma, Raleigh, USA, 6 UCB Pharma, Brussels, Belgium, 7Department of Medicine, UCSF Medical Center, San Francisco, USA

corticosteroids and methotrexate were the most common relevant concomitant medications reported during pregnancy. Most clinical trial subjects had low to moderate disease activity at conception (median CDAI 184.9 for 22 CD subjects, DAS28(ESR) range 1.1–6.1 for 7 RA subjects). Miscarriages were not associated with high disease activity at conception. Conclusions regarding concomitant medications and disease activity are limited due to low numbers. Currently available data from pregnant women exposed to CZP reported outcomes similar to what is expected in the general population.1 However, additional data from large numbers of pregnant women exposed to CZP are required to fully evaluate the safety and tolerability of CZP in pregnancy. Reference: 1. Ventura et al. Natl Vital Stat Rep 2012;60:1-21.

APLAR-0501

Place and significance of molecular diagnostics in Rheumatoid arthritis Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNF approved in several countries for the treatment of RA and CD. The objective of this study was to provide additional information on the primary pregnancy outcomes for women exposed to CZP through a retrospective safety database analysis. The UCB safety database was searched for all medically confirmed cases of pregnancy (N = 294), including both clinical trial and post-marketing reports, through March 6 2012. The proportion of live births, miscarriages and elective terminations for women directly exposed to CZP before and during pregnancy was examined. Exposure to concomitant medications (pooled across indications) and disease activity prior to conception was reviewed for pregnancies that occurred in clinical trial subjects (n = 57). 152/294 reported pregnancies had known outcomes, with 139 following maternal CZP exposure. 66% were from the US. Median gestational age was 38 weeks. Reported pregnancy outcomes and maternal demographics are presented in Table 1. There were 2 cases of congenital disorder and a single neonatal death (medical review concluded connection to CZP exposure unlikely) in 103 live births. Where data were available from clinical trial subjects,


VA KOZLOV, AE SIZIKOV, NV PRONKINA, VS SHIRINSKY, IV SHIRINSKI, EY RYKOVA Institute of Clinical immunology, Novosibirsk, Russia Numerous data give evidence on leading role of immune system disorders in Rheumatoid arthritis (RA) pathogenesis with the priority of Th1 and Th17 T cells hyperactivity and increased production of Th1/Th17 proinflammatory cytokines. At the same time molecular mechanisms of proinflammatory cytokines effect realization such as neopterin, homocysteine, tryptophan, cell-free DNA production should be evaluated in basic and clinical Rheumatology. Each of above mentioned nonspecific factors reflects different cytokine-induced immunopathogenetic aspects of RA. On the other hand complex evaluation of neopterin, homocysteine, tryptophan and other systemic inflammation biomarkers levels could optimize RA diagnostic criteria and RA treatment monitoring. The results of systemic inflammation biomarkers research in RA will be presented and discussed.

29

FP1B - Free Paper 1B: Vasculitis/Rheumatoid Arthritis

FP1B - Free Paper 1B: Vasculitis/Rheumatoid Arthritis

APLAR-0076

Behcets disease in Azerbaijan A KHABBAZI, F KARKON, H KAVANDI, M HAJIALILOO, M JAFARI NAKHJOVANI Internal Medicine, School of Medicine Tabriz University of Medical Sciences, Tabriz, Iran ~ disease (BD) is a chronic inflammatory disease that Introduction and Objectives: BehcetOs involves ocular, articular, vascular, cutaneous, intestinal, urogenital and neurological systems. We evaluated the demographic and clinical manifestations of BD in 127 patients in rheumatology clinic of Tabriz University of Medical Sciences Material and Methods: In a cross sectional study we considered the demographic and clinical findings of patients with BD and compared them between females and men. BD diagnosed by the International criteria of BD. Disease activity was measured by Iran Behcet’s Disease Dynamic Activity Measure. Results: Male to female ratio was 1.6:1, the age of disease onset was 25.8 9.9. The first symptom of disease was oral aphthous ulcer in 71.2%, genital aphthous ulcer in 21.3%, ophthalmic involvement in 13%, pseudofolliculitis in 6.3%, articular involvement in 3.1%, erythema nodosa in 2.4%, and vascular involvement in 0.8%. HLAB5 was positive in 55.9%. The most frequent symptoms were oral aphthous ulcer (93.7%), eye involvement (54.3%), genital aphthous ulcer (49.6%), positive pathergy test (33.9%), pseudofolliculitis (25.9%), erythema nodosa (15.7%), and musculoskeletal involvement (14.2%). Severe vision loss including vision 100 IU/mL). Conclusion : Anti-CCP antibody positivity and titers prior to treatment were not associated with the efficacy of the ABT therapy. Our results in patients with high anti-CCP antibody titers suggested that anti-CCP titers might be associated with the clinical course of the ABT therapy.


57

APLAR-0170

Efficacy and safety of rituximab-biosimilar in rheumatoid arthritis S BANDYOPADHYAY Department of Medicine, Apollo Gleneagles Hospital Kolkata, Kolkata, India

Clinical Rheumatology – T05: Rheumatoid arthritis – non biologic treatment

Clinical Rheumatology – T05: Rheumatoid arthritis – non biologic treatment

APLAR-0040

APLAR-0164

Atorvastatin in treatment of rheumatoid arthritis

DMARD combination therapy in RA after infliximab discontinuation

S SALMAN1, HM JAWAD2, S SHUKUR2

H KAMEDA1, T KURASAWA2, H NAGASAWA3, M KISHIMOTO4, K AMANO3, T TAKEUCHI2

1 Rheumatology, College of Medicine of Baghdad, Baghdad, Iraq, 2Pharmacology, College of Medicine of Baghdad, Baghdad, Iraq

Background: Rheumatoid arthritis (RA) is a common chronic inflammatory disorder that characterized by synovitis, articular destruction, and many systemic extra articular features. It is associated with a high rate of morbidity and mortality due to accelerated atherosclerosis and increased cardiovascular risk. Atorvastatin is well known anti dyslipidemic agent that might have a valuable anti-inflammatory and immune modulatory functions in RA. Objectives: The present study was performed to evaluate the anti-inflammatory effect of atorvastatin when used as adjuvant therapy to methotrexate and etanercept in Iraqi patients with moderate to highly active RA. Patients and Methods: A double blind randomized placebo – controlled clinical trial at which 100 patients of both genders with active RA who were on MTX and etanercept for at least 1 month, were divided into two groups to receive 20 mg atorvastatin tablet or placebo capsule for three consecutive months. Only 49 patients completed the 3 months trial, 25 patients in atorvastatin and 24 patients in placebo group. All patients were clinically evaluated by measuring swollen joint count (SJC), tender joint count (TJC), visual analogue scale (VAS) and disease activity score (DAS28). Blood samples of RA patients were evaluated for erythrocyte sedimentation rate (ESR), C reactive protein (CRP) at baseline, monthly and at the end of the study. Results: RA patients undergoing 20 mg atorvastatin treatment showed a significant (P < 0.05) reduction in C- reactive protein level (CRP), swollen joint count (SJC) and tender joint count (TJC) compared to placebo. In addition, atorvastatin reduce erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) and disease activity score (DAS28) more than placebo but without achieving statistical significance (P > 0.05). Conclusions: It can be concluded that 20 mg atorvastatin is a safe and well-tolerated drug that has modest anti-inflammatory effect in patients with moderate to highly active RA.

APLAR-0075

Monitoring of transaminases in patients treated with methotrexate A KHABBAZI, S KOLAHI Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Objective: Considering the safety of liver transaminases monitoring every 12 weeks in patients with inflammatory connective tissue disorders who are treated with methotrexate (MTX). Methods: In a retrospective study, the data from the rheumatic patients receiving MTX were analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the baseline and every 12 weeks. The patients were classified according to their ALT and AST levels as the following: no change, 1–2 times increase, 2–3 times increase, and more than 3 times increase in their ALT or AST levels. Based on the physician’s decision on the dose of MTX, the patients were classified into: no change in MTX dose, decrease in MTX dose, and discontinuation of MTX. Based on the physician’s final decision about the continuation of MTX, the patients were classified into one of the following groups: continuation of MTX without MTX dose reduction, MTX dose reduction, MTX discontinuation due to liver complication, and MTX discontinuation due to other reasons. Results: A total of 809 patients who were on MTX were included in the study. The mean follow-up duration and the mean duration of treatment with MTX were 31.22 and 19.76 months respectively. The mean accumulation dose of MTX was 865.85 mg. Due to the increase in the level of transaminases in 26 (3.2%) of the patients, the dose of MTX was reduced; and in 9 (1.1%) cases it was temporarily discontinued. In the follow-up of the patients with elevated transaminases, they returned to normal limits in 90 (99.5%) of the patients; and only in 4 of the cases (0.5%) they remained elevated and MTX was discontinued. The probability of the patients remaining on MTX for 5 years without discontinuation for liver complications was 98.5% Conclusion : Liver transaminases monitoring every 12 weeks for MTX treated patients is safe.

1 Division of Rheumatolgy, Department of Internal Medicine, Toho Uiversity Ohashi Medical Center, Tokyo, Japan, 2Division of Rheumatolgy, Department of Internal Medicine, Keio University, Tokyo, Japan, 3Division of Rheumatolgy, Department of Internal Medicine, Saitama Medical Center, Kawagoe, Japan, 4RA Marketing, Santen Pharmaceutical Co. Ltd., Ofukacho, Japan

Objectives: We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARD) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare. Methods: RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with Creactive protein) scores 0.05). The disease activity of RA reduced in both groups, but SSBH group was a little better than the western medicine group (Fig. 1). The results demonstrated that the combined application of SSBH could reduce laboratory indices of patients more lasting and effectively than western medicine used only (Fig. 2). There was no significant difference between the two groups in radiographic progression, combined application of SSBH might improve the bone destruction. The security of SSBH group was better than that of western medicine group. Conclusions: The combined application of SSBH can reduce the laboratory index and disease activity of RA, improve or delay bone destruction of patients more effectively compared with DMARDs or (and) the biological treatments used simple, in short, combined application can improve the therapeutic effect, reduce adverse reactions obviously, and the safety also improves, so it’s necessary to further study. More samples are needed to have a randomized prospective study for long time.

Methods : RASFs that treated with SSBH and normal saline (NS) were respectively used as target cells and adsorption cells for subtraction biopanning from a phage display peptide. After panning three times, monoclonal phage were picked, amplified and purified. The affinity of positive and specific binding clones were preliminarily identified by ELISA, and the identified clones were sequenced and biological analyzed. Results : After three pannings, positive phage was enriched 100 times compared with the original phage, and 32 phage clones were randomly selected for DNA sequence analysis, and the peptide of SGVYKVAYDWQH was enriched 56% (18/32). The sequences were submitted BLAST for homology search and analysis. We preliminarily identificated its affinity of SSBH and NS in RASFs treatment by ELISA, showing that the highest affinity was SGVYKVAYDWQH (OD value of 0.382 0.020) in SSBH treated RASFs with control NS group affinity (OD value of 0.206 0.015), P < 0.05. Biological analysis showed that the proteins of Vaspin, myotubularin-related protein 14 (MTMR14), DST protein and CAD protein were highly correlated with the SGVYKVAYDWQH. Conclusions : A high-affinity dodecapeptide specific for RASFs treated with SSBH is obtained using phage display peptide library, and the related proteins is analyzed. So we think SSBH maybe play an important role in RASFs through inhibiting the expression of Vaspin and CAD protein. Meanwhile, the protein of DST and CAD were associated with cell structure, movement and migration. Whether SSBH can intervene athletic ability, cell migration of RASFs, and block the initiative proliferation of RASFs, requires further study.

APLAR-0411

Screening the target of Sanshui Baihu decoction affecting on RA CH XIAO, C PAN Department of Rheumatology, TCM-Integrated Hospital of Southern Medical University, Guangzhou, China Objective : To find the polypeptide that specifically binding to Rheumatoid Arthritis synovial fibroblasts (RASFs) cultured with Sanshui Baihu decoction (SSBH), and to obtain protein targets treating rheumatoid arthritis.

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Clinical Rheumatology – T06: Systemic lupus erythematosus, Sjogren’s and antiphospholipid syndrome – therapies


APLAR-0008

Roles of mTOR signaling in cellular senescence of BM-MSCs from SLE Z GU Rheumatology, Affiliated Hospital of Nantong University, Nantong, China The abnormal bone marrow (BM)-derived mesenchymal stem cells (MSCs) maybe associated with the pathogenesis of systemic lupus erythematosus (SLE). Cell cycle arrest coupled with hyperactive mammalian target of rapamycin (mTOR) leads to cellular senescence. Thus, we primarily confirmed that the mTOR signaling of SLE BM-MSCs was hyperactive in comparison with that of MSCs from normal subjects. Then, we found that the effect of mTOR inhibitor rapamycin (RAPA) and mTOR siRNA could decelerate the senescent features of SLE MSCs in time-dose dependence and induced cell cycle arrest no by p53/p21-dependent pathways but by p27-dependent pathways. When purified CD4+ T cells were incubated with RAPA-treated and si-mTOR MSCs of SLE, the ratio of regulatory T (Treg)/T helper type 17 (Th17) cells was significantly increased by enhancing regulatory cytokines (IL-10 and TGF-b) and reducing pro-inflammatory cytokines (IL-17 and IL-6). Besides, BM-MSCs from SLE treated with rapamin have therapy effect on lupus mice. Taken together, our study indicated the mTOR signaling may play a critical role in SLE BM-MSC senescence, which suggested allogenic MSCs treated with RAPA transplantation (MSCT) appears to be a feasible and secure therapy strategy in lupus-prone mice.

APLAR-0061

Methods: We recruited 15 patients treated with add-on tacrolimus for the minor flares (Tacrolimus group). The minor flare was defined as an increase in SLEDAI remained between 3 and 11. As controls, sex, age, and dose of glucocorticoids and SLEDAI at flare matched 15 patients administered increased dose of glucocorticoids for minor flares were also recruited (Glucocorticoid group). All patients were maintained remission for 3 months before the minor flares with glucocorticoids (≤10 mg/day) and/or immunosuppressants except calcineurin inhibitors. Results: The clinical characteristics of baseline were comparable between the two groups. Azathioprine (n = 2), mizoribine (n = 2), mycophenolate mofetil (n = 1), and methotrexate (n = 1) was used concomitantly in Tacrolimus group. Whereas, in Glucocorticoid group, azathioprine (n = 1), mycophenolate mofetil (n = 1) or cyclophosphamide (n = 1) was also used. After 12 months, SLEDAI was improved to the level before the flares in 73% of Tacrolimus group and 80% of Glucocorticoid group. There was no significant difference in SLEDAI at 12 months between the two groups (Tacrolimus group: 4.1 vs. Glucocorticoid group: 3.1). Two patients in both groups developed flares (the definition of the flare is administration of other immunosuppressants or increased dose of glucocorticoids after the improvement of SLEDAI). One patient in Tacrolimus group developed pleurisy 8 months later and the other patient developed new rash 10 months later. In Glucocorticoid group, new rash was observed 5 months later in one patients and myositis was observed 4 months later in the other patient. Tacrolimus discontinued in only 1 patient because of fatigue. Conclusion: Our study suggested that the effectiveness of tacrolimus for the treatment of SLE with minor flares was not inferior to glucocorticoid without increasing frequency of adverse effects.

APLAR-0128

Role of IL-33/ST2 axis in endothelial cell injury of lupus nephritis

In-hospital outcomes of methylprednisolone pulse therapy in SLE

SL YU, CH HUANG, WH HUANG, CH HUANG, ZL WANG, Y TAO

A MAGBITANG, EO SALIDO, AKG RUBIO

Department of Rheumatology, The Second Affiliated Hospital of Guangzhou Medical University Guangzhou Medical Universtiy, Guangzhou, China

Medicine, Section of Rheumatology, University of the Philippines, Philippine General Hospital, Manila, Philippines

Background: “Alarmins” are prototypic endogenous pro-inflammatory factors as they are released from necotic cells and provoke local damage or systemic inflammation. Evidences are accumulating to support the inclusion of “Alarmins” as targets of autoreactivity as well as inducers in the pathogenesis of Systemic Lupus Erythematosus (SLE). Interleukin (IL)-33 is a novel member of the family of “Alarmins” because of its characteristics and functions in mediating host immune responses. On this background, we sought to determine the role of IL-33/ ST2 axis in lupus pathogenesis. The role of IL-33/ST2 axis has not previously been described in lupus nephritis. Objectives: This project will study the followings: (1) To determine whether IL-33 was present in renal glomerular endothelial cells; (2) To assess the functional and intracellular signal transuction mechanisms regulating the link between IL-33/ST2-mediated innate immunity and inflammation in CD4+ T cells-endothelial cells co-culture system of lupus patients. Preliminary results: Immunofluorescence (IF) for IL-33 in the kidney were performed in both MRLlpr lupus mice and C57BL/6J mice. On double staining for IL-33 and lectin, IL-33 was clearly seen in glomeruli and also in peritubular areas. To determine whether the IL-33 staining in glomeruli and peritubular areas was in endothelium, double IF staining for IL-33 and von Willebrand factor (vWF) was performed. IL-33 co-localized with vWF in glomeruli and in peritubular areas. The increased levels of IL-33 mRNA transcripts were detected in kidney of MRLlpr lupus mice compared with C57BL/6J mice. Expression of cell-surface ST2 was increased on the CD4+ T cells of lupus patients when compared with healthy controls. Serum sST2 level was significantly higher in SLE patients with flare than those without flare (P < 0.05). Conclusions: As a result of external stimuli or infection, renal glomerular endothelial cells undergo cellular death and release the “Alarmin”, IL-33, to alert the lupus immune system. Released IL-33 interact with their target cells, CD4+ T cells via their specific receptor ST2 to subsequently induce innate and adaptive responses, activate inflammatory pathways in the pathogenesis of lupus nephritis.

APLAR-0087

Background: Methylprednisolone Pulse Therapy (MPPT) is standard of care in the management of severe systemic lupus erythematosus (SLE). This treatment, though, is considered a double-edged sword due to its life-threatening adverse effects. Renal disease, liver disease and high dose of the drug are factors proposed to adversely affect outcomes of patients treated with MPPT. Despite the widely-accepted use of MPPT, there are no reports describing the outcomes from its use among Filipinos with SLE. General Study Design: Retrospective. Population: Adult patients with SLE who were admitted in Philippine General Hospital and underwent MPPT from January 2008 to December 2012. Methods : Patient demographics, disease characteristics on admission, indications for MPPT and in-hospital outcomes were extracted. Analysis: Chi square test and Fisher’s exact test were used to elicit association of population characteristics to outcomes. Results: Forty-two patients with SLE who underwent MPPT are included. Majority are females (98%) and most (60%) underwent MPPT within 1 year of SLE diagnosis. High disease activity is seen at the time of MPPT with a mean Mex-SLEDAI score of 14.69. Infection (83%) is the most common comorbidity. Anemia, hypoalbuminemia and significant proteinuria are the most common laboratory abnormalities. The top indication for MPPT is nephritis (83.3%). The dose received by the majority (66.7%) is 1 g/day for 3 days, which is a high dose. Improvement rate is 76% but the in-hospital complication rate is 64% and mortality rate is 21%. Patients with in-hospital complications have significantly lower absolute lymphocyte count (P = 0.013), serum albumin (P = 0.04) and greater 24-h proteinuria (P = 0.04) at baseline. High-dose MPPT is significantly associated with in-hospital complications (P = 0.04) but not mortality. Nephritis (P = 0.04) and low platelet counts at baseline (P = 0.01) are associated with mortality.

APLAR-0261

The effectiveness of tacrolimus for minor flares of SLE

Epratuzumab: improvements in disease activity and quality of life

H WATANABE1, R YAMANAKA2, KE SADA1, S HIRAMATSU1, Y YAMAMURA1, E KATSUYAMA1, T KATSUYAMA1, MT NARAZAKI1, NT TATEBE1, K SUGIYAMA1, KS WATANABE1, H WAKABAYASHI1, T KAWABATA1, J WADA1, H MAKINO1

K HOBBS1, V STRAND2, DJ WALLACE3, K KALUNIAN4, E NIKAI5, B KILGALLEN6, S BONGARDT5, WA WEGENER7, DM GOLDENBERG8

1

Medicine and Clinical Science, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama City, Japan, 2Internal Medicine, Himeji Red Cross Hospital, Himeji City, Japan

Objectives: We assess the effectiveness of tacrolimus for minor flares of SLE.


1

Denver Arthritis Clinic, Denver, USA, 2Division of Immunology/Rheumatology, Stanford University, Palo Alto, USA, 3Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, USA, 4Department of Medicine, UCSD School of Medicine, La Jolla, USA Two randomized, double-blind trials (ALLEVIATE1 and 2) of epratuzumab, a monoclonal antibody targeting CD22, in lupus patients were terminated due to interrupted drug supply.

61


SL0006 was an open-label extension for ALLEVIATE patients. We report results from SL0006 over a median of 210 weeks’ treatment (~4 years). ALLEVIATE patients were eligible to receive 12-week cycles of epratuzumab [360 mg/m2 at Days 1 and 8; assessments every 4 weeks from screening (Visit 1; V1)]. Timepoints were compared to ALLEVIATE baseline (BL) and V1. Of 29 patients, 10 had severe (BILAG A) SLE activity in ≥1 body/organ system and 19 had moderate (BILAG B) activity in ≥2 body/organ systems. Median (range) delay in epratuzumab dosing between ALLEVIATE and SL0006 was 52.6 weeks (11.1*93.0). Median (range) study duration was 210.4 weeks (14.1*275.4) (~4 years). Median BILAG total scores and numbers of BILAGA/B in each body/organ system were reduced between BL and V1; most V1 BILAG A/ B grades improved to C/D at least once. Median (95% CI) time to new severe lupus flare (1 new A or 2 new Bs) was 0.61 years (0.38, 1.47). Median (range) of circulating B-cell counts (cells/lL) decreased from BL to V1 (Table 1); after two years, median percentage change stabilized at 55%*65%. Median corticosteroid dose decreased from BL to V1 (Table 1) and was maintained throughout SL0006. Mean PCS, MCS and most SF-36 domain scores increased (Table 2). Improvements in PCS and in three domains (Role Physical, Bodily Pain, Social Function) exceeded MCID throughout SL0006. All patients reported ≥1 AE, and 14 (48.3%) ≥1 SAE. In this open-label extension study, continued administration of epratuzumab for ~4 years maintained or improved SLE disease activity. Clinically meaningful improvements in HRQoL were sustained throughout the study, and epratuzumab was generally well tolerated with no new safety signals.

203 patients received a median 845 (range 75*1185) days’ exposure to epratuzumab over a median 10 treatment cycles (range 1*14). Median CS dose was 10.0 mg/day at EMBLEMTM baseline and SL0008 screening, and 5.0 mg/day at Week 116 (n = 112; last timepoint with >50% of patients). The proportion of patients requiring >7.5 mg/day decreased from SL0008 baseline to Week 116, whilst the proportion of patients receiving 7.5 mg/day. Epratuzumab had an acceptable safety profile with no new safety signals. 1. Wallace DJ et al. Ann Rheum Dis (2013) [Epub]

APLAR-0285

Efficacy and safety of belimumab in patients with SLE: a meta-analysis

APLAR-0263

Epratuzumab: long-term safety and effect on corticosteroid use 1

2

3

4

D WALLACE , J ORDI-ROS , M NEUWELT , K KALUNIAN , B KILGALLEN5, S BONGARDT6, M PETRI7, M PIKE8, S JEKA9, C GORDON10, V STRAND11, J SHAO12 1

Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, USA, 2Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Spain, 3Internal Medicine, East Bay Rheumatology Medical Group, Barcelona, Spain, 4 Division of Rheumatology, UCSD School of Medicine, La Jolla, USA, 7School of Medicine, Johns Hopkins University, Baltimore, USA, 8Harvard Medical School, Harvard University, Cambridge, USA, 9Clinical Department of Rheumatology and Connective Tissue Diseases, University Hospital No. 2, Bydgoszcz, Poland, 10 Rheumatology Research Group, University of Birmingham, Birmingham, UK, 11 Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, USA, 12UCB Pharma, Slogh, UK Safety and efficacy of epratuzumab, a monoclonal antibody targeting CD22, were assessed in EMBLEMTM, a 12-week phase IIb study in patients with moderate-to-severe systemic lupus erythematosus (SLE).1 SL0008 (NCT00660881) was an open-label extension of EMBLEMTM. The objective was to evaluate the safety profile and effect on corticosteroid (CS) use of long-term epratuzumab treatment in moderate-to-severe SLE. EMBLEMTM patients who completed 12 weeks’ blinded treatment, or discontinued due to lack of efficacy but completed ≥8 weeks, were eligible for SL0008. Patients received 1200 mg epratuzumab at Weeks 0 and 2 of 12-week cycles. Evaluation visits were at Weeks 4 and 8 of each cycle. Safety variables included adverse events (AEs), infusion reactions and infections. CS doses were monitored and converted to prednisone equivalent dose. Data are summarized using descriptive statistics.

62

S AGUSTIN Internal Medicine, San Juan Medical Center, San Juan, Philippines Background of the Study: Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by abnormal activation pathways in adaptive immunity cells. B lymphocyte stimulator (BLyS) contributes to B cell proliferation and differentiation. Belimumab, an IgG monoclonal antibody, binds to soluble active form of BLyS, thus could provide therapeutic benefits in patients with SLE. Objective : To review the effects of Belimumab plus standard therapy on the scores in SELENA (Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Physician Global Assessment (PGA), and on occurrence of British Isles Lupus Assessment Group (BILAG). It also aims to evaluate the safety of this medication in terms of occurrence of serious infections. Methodology: Randomized clinical trials were retrieved using PubMed and Cochrane using terms SLE, Belimumab, and Safety profile of Belimumab. Two clinical trials were included evaluating the efficacy and safety of Belimumab. Results: Two double blind placebo controlled RCTs (BLISS 52 and BLISS 76) investigated 1684 SLE patients. Meta-analysis of pooled 52-week 4 point reduction in SELENA-SLEDAI score BLISS results revealed that 10 mg/kg Belimumab plus standard therapy statistically decreased SLE activity compared to standard therapy plus placebo (OR 1.290, 95% CI 1.047– 1.589). No statistical significance noted between placebo and Belimumab in terms of worsening PGA, occurrence of new BILAG, and serious infections. However, Belimumab exemplified more patients who had no worsening PGA and occurrence of new BILAG. Conclusion : Belimumab plus standard therapy improved SLE activity in terms of reduction of SELENA-SLENDAI scores, no worsening of PGA, and prevention of occurrence of BILAG, and was generally tolerated by SLE patients. Keywords: Systemic Lupus Erythematosus, Belimumab, Safety



APLAR-0436

Kidney transplant outcomes in Filipino lupus nephritis patients L LUGUE-LIZARDO1, S NAVARRA2 1

Internal Medicine Department, Section of Rheumatology, UST Hospital, Pasig, Philippines, 2Internal Medicine Department, Section of Rheumatology, UST Hospital, Manila, Philippines

Objective : Determine renal outcomes and graft survival of renal transplant recipients with end stage renal disease (ESRD) secondary to lupus nephritis (LN). Methods: We retrospectively reviewed data from University of Santo Tomas (UST) systemic lupus erythematosus (SLE) database of LN patients with ESRD who underwent kidney transplantation (KT). Serum creatinine, urinalysis and estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were analyzed. Results: Included were 12 patients (9 females) with mean age 23 5.9 years at LN, mean age 30 7.9 years at KT, mean duration 88.7 73.4 months from LN to KT. Two patients opted preemptive KT with eGFR 10 and 13 mL/min/1.73 m2 prior to KT. Ten patients underwent non-preemptive KT with eGFR 4–16 mL/min/1.73 m2 prior to KT. Of these, 4 had hemodialysis (HD) 9 months and below, 4 had mean HD duration 22.6 1.89 months and 2 had peritoneal dialysis (PD) with mean duration of 60 months. Preemptive KT patients’ eGFR were 90 and 94 mL/min/1.73 m2 post-KT. Non-preemptive KT patients on shortened HD showed post-KT eGFR at 84, 107, 80 and 95 mL/min/1.73 m2. One patient who was noncompliant to medications had rejection on the sixth year requiring HD. Among those on prolonged dialysis, post-KT eGFR were 84, 57, 51, 80 and 43 mL/min/1.73 m2. Two patients expired on the second month and second year post-KT (1 with sepsis and antiphospholipid syndrome, the other with LN recurrence confirmed by repeat biopsy). The surviving 10 patients have an ongoing graft survival ranging from 2 years to 22 years. Conclusion : This small series suggests that preemptive and shortened dialysis KT patients showed a trend for better renal functions and graft survival post-KT. Two patients with nonpreemptive KT and evidence of active disease died within 2 years of KT, emphasizing the importance of disease quiescence prior to KT.

APLAR-0438

Cyclophosphamide vs. MMF as lupus nephritis induction in Filipinos L LUGUE-LIZARDO, S NAVARRA Internal Medicine Department, Section of Rheumatology, UST Hospital, Manila, Philippines Objective : Describe the renal responses of lupus nephritis (LN) patients who completed the induction phase of intravenous cyclophosphamide pulse therapy (CyPT) using low-dose Euro-Lupus Nephritis Trial (ELNT) vs high-dose National Institutes of Health (NIH) regimens vs mycophenolate mofetil (MMF) in the treatment of LN Methods: We retrospectively reviewed data of adult patients with LN who completed induction therapy using CyPT either ELNT or NIH protocol for 6 doses or MMF regimen for 6 months from January 2007 to December 2012. Renal responses were described as complete, partial, non-response to therapy or deterioration of renal function based on serum creatinine and level of proteinuria. Responses were recorded at 2 time points: immediately after completion of induction and 6 months after induction.


Results: Included were 126 patients (113, 89.7% females) with mean age of 31 9.2 years (range 18–57), mean disease duration of 15.4 32.6 months (range 0–221). Thirty three (26.2%) were on ELNT, 52 (41.3%) on NIH and 41 (32.5%) on MMF regimens. Immediately after completion of induction, complete response was seen in 42.4%ELNT, 57.7%NIH and 14.6%MMF; partial response in 27.3%ELNT, 19.2%NIH and 46.3%MMF; non- response in 21.2%ELNT, 13.5%NIH and 24.4% MMF; deterioration in 9.1%ELNT, 9.6%NIH and 14.6% MMF; P = 0.005. At 6 months following completion of induction, complete response was seen in 18.2%ELNT, 53.8%NIH, 61%MMF; partial response in 15.2%ELNT, 21.2%NIH, 24.4%MMF; non-response in 45.5% ELNT, 13.5%NIH, 7.3%MMF; deterioration in 21.2% ELNT, 11.5%NIH, 7.3%MMF; P < 0.001. Adverse events were reported in 42.3% on NIH, 39.4.% on ELNT and 39% on MMF including infections, leucopenia, hair loss and amenorrhea. Conclusion : High-dose CyPT was associated with more complete renal responders immediately post-induction therapy while MMF regimen showed the highest number of complete renal responders in the 6 months following induction among Filipino LN patients. Most adverse events were observed with high-dose CyPT regimen.

APLAR-0464

The mechanism of anti-malarial drugs down-regulating IFN-a level O JIN, X ZHANG, HY HUANG, DF LIN, LK FANG, ZT LIAO, ML QIU, CC HOU, ZM LIN, JR GU Department of Rheumatology, Affiliated 3rd Hospital of Sun Yat-san University, Guangzhou, China Background: SLE is an autoimmune disease whose innate immune system stimulated by endogenous nucleic acids through toll-like receptor (TLR) pathway, resulting in the production of IFN-a. Although the mechanisms are still unkown, most of experts agree that antimalarial drugs block TLR. Objectives: To explore whether and how anti-malarial drugs, combined with glucocorticoid, influence the production of IFN-a in human peripheral blood mononuclear cells (PBMCs). Methods: Freshly isolated PBMCs of healthy donors were stimulated with the TLR-9 agonist CpG ODN-2216, then incubated with different kinds of anti-malarial drugs (hydroxychloroquine (HCQ), quinacrine(Qn) or both) and/or different doses of glucocorticoid (hydrocortisone). The changes in the expression of TLR7, TLR9, MyD88, IKK-a, AP1, NF-jB and IFN-a were detected by real time PCR. Results: A. HCQ or Qn alone or combined together significantly reversed the elevation of IFN-a caused by ODN 2216 (P < 0.001, respectively), the results were same when combined with low and middle doses of glucocorticoid (P < 0.001, respectively), but not with high dose of glucocorticoid. B. Anti-malarial drugs could not down-regulate the increased expression of TLR9, IKK-a and NF-jB of TLR-9 stimulated PBMCs treated by high dose of glucocorticoid. C. Anti-malarial drugs had no effects on the expression of TLR7, TLR9, MyD88, IKK-a, NF-jB and AP1 of PBMC stimulated by ODN 2216. Conclutions: 1. Anti-malarial drugs hamper the critical pathogenesis of lupus that TLR9 recognition of nucleotides (ODN 2216) elevates the IFN-a expression of PBMCs. 2. The elevation of IFN-a caused by high doses of glucocorticoid may relate to the increased expression of TLR9, IKK-a and NF-jB of PBMC stimulated by ODN 2216. 3. Anti-malarial drugs have no effects on the expression of TLR7, TLR9, MyD88, IKK-a NF-jB and AP1 of PBMC stimulated by ODN 2216.

63

Clinical Rheumatology – T07: Systemic lupus erythematosus, Sjogren’s and antiphospholipid syndrome – clinical aspects, comorbidities and complications


APLAR-0036

APLAR-0064

Metabolic syndrome in Indian SLE patients

Interferon-gamma release assay in patients with rheumatic diseases

M THABAH1, BS BHAT1, VS NEGI2, AK DAS1, Z BOBBY3

SJ KEE1, YW PARK2, HJ JUNG2, TJ KIM2, YN CHO2, HM JIN2, MJ KIM2, KJ PARK2, SJ LEE2, N KIM3

1 Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, 2Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, 3Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India

Objectives: To find the frequency of metabolic syndrome (MS) among SLE cases compared to controls and to see if there is association of MS with SLE disease activity and damage Methods: 82 SLE patients and 82 age and sex matched controls were studied. MS was defined by the national cholesterol education program Adult treatment panel III (NCEP ATP III), Consensus definition for Asian Indians and WHO 1999 criteria, and association with SLE characteristics, disease activity and damage were examined. Results: Age in years (mean SD) was 28.7 6.8 and 29.3 9.3 in SLE and controls. All patients were females. MS was present in 24.39% SLE cases and 12.19% controls (P < 0.04) by NCEP ATP III criteria; 29.26% cases and 19.5% controls (P = 0.145) by Consensus definition for Asian Indians; 18.2% cases and 7.31% controls (P < 0.035) by WHO 1999 criteria. MS components- Abdominal obesity (waist circumference >80 cm), hypertension, impaired fasting glucose, triglycerides >150 mg/dL, and HDL 6 h increased the odds ratio of indeterminate IGRA results. In contrast, the automated ELISA processor, ankylosing spondylitis, and the use of a non-steroidal anti-inflammatory drug decreased the likelihood of indeterminate IGRA results. Lymphopenia, thrombocytopenia, anemia, and hypoalbuminemia were significantly associated with indeterminate IGRA results. Multivariate analysis revealed that SLE, use of sulfasalazine or a TNF-a inhibitor, and an automated ELISA system were significantly independent predictors of indeterminate IGRA results. Conclusion: The proportion of indeterminate results in patients with rheumatic diseases is not infrequent. Careful attention to the pre-analytical conditions should minimize the indeterminate results. Automation of the ELISA process seems to be a promising solution to decrease the rate of indeterminate response.

APLAR-0093

Echocardiographic abnormalities in SLE patients in Saudi Arabia APLAR-0063

A AL-ARFAJ, N KHALIL

MAIT cell deficiency in systemic lupus erythematosus YW PARK1, SJ KEE2, YN CHO1, TJ KIM1, HM JIN1, MJ KIM1, HJ JUNG1, KJ PARK1, SJ LEE1, N KIM3 1

Department of Rheumatology, Chonnam National University Hospital, Gwangju, Korea, 2Laboratory Medicine, Chonnam National University Hospital, Gwangju, Korea, 3Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. Here, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and doublenegative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index (SLEDAI) and 28-joint disease activity score (DAS28). Interestingly, MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. Interferon-c production in MAIT cells was impaired in SLE patients, but it was preserved in RA patients. In SLE patients, MAIT cells were poorly activated by a-galactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In RA patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.

64

Medicine, King Saud University, Riyadh, Saudi Arabia Background: Cardiac manifestations are one of the most important clinical features of SLE.1 Pericardial involvement is the most common.2 Objectives: To study the echocardiographic findings in SLE patients in a tertiary hospital in Saudi Arabia. Methods: SLE patients (fulfilling ACR criteria) attending King Saud university hospital clinics, Riyadh were studied retrospectively. Results: A total of 624 SLE patients [566 (90.7%) females and 58 males (9.3%). The mean age was 34.3 11.9 (range 8–71) years and mean SLE duration was 9.3 5.3 (range 0.3– 30) years. The echocardiographic findings are summarized in Table 1. A total of 208 (33.3%) SLE patients manifested 409 cardiac abnormalities. Pericardial involvement (pericardial effusion or pericarditis) was the most frequent [130 (20.8%)] patients including pericardial tamponade in 1 patient. The next was mitral valve regurgitation occurring in 104 (16.7%) followed by tricuspid valve regurgitation in 67 (10.7%), aortic valve regurgitation in 36 (5.8%), ventricular hypertrophy in 22 (3.5%) and mitral valve prolapse in 21 (3.4%). Conclusions : Echocardiographic abnormalities were observed in 33.3% of our SLE patients. Pericardial involvement (20.8%) was the most frequent, mitral valve regurgitation being the most common valvular defect (16.7%). References: 1. Moder KG, Miller TD, Tazelaar HD. Cardiac involvement in systemic lupus erythematosus. Mayo Clin Proc 1999; 74:275. 2. Doherty, NE, Siegel, RJ. Cardiovascular manifestations of systemic lupus erythematosus. Am Heart J 1985; 110: 1257*1265. Table 1. Echocardiographic abnormalities in SLE patients (n = 624) Echocardiographic abnormalities Pericardial involvement Mitral regurgitation Tricuspid regurgitation Aortic regurgitation Mitral valve prolapse Endocarditis (including Libman Sacks) Libman Sacks endocarditis Myocarditis Ventricular hypertrophy Dilated atrium

Number

Percentage (%)

130 104 67 36 21 9 4 5 22 11

20.8 16.7 10.7 5.8 3.4 1.4 0.6 0.8 3.5 1.8



APLAR-0106

Anti MAP-2 antibody in CSF is a novel diagnostic biomarker for NPSLE Y YAMADA, K NOZAWA, S NAKANO, A MITSUO, K HIRUMA, K DOE, Y MATSUKI, K YAMANAKA, I SEKIGAWA, Y TAKASAKI Internal Medicine and Rheumatology, Juntendo University, Tokyo, Japan Backgroud: Anti microtube associated protein 2 (MAP-2) antibody has been reported to be found in sera with SLE patients especially having neuropsychiatric manifestations. In some cases, it is hard to diagnose NPSLE because clinicians have to exclude clinically many other diseases such as viral infection or steroid psychosis. Multiple diagnostic examinations such as IL-6 measurement in cerebrospinal fluid (CSF) have been used for diagnosis with NPSLE to date, however, findings from these examination are not specific for NPSLE. Therefore, novel diagnostic biomarkers have been expected to be established. Herein, we conducted this study to clarify that anti-MAP-2 antibody in cerebrospinal fluid can be used for a diagnostic biomarker of NPSLE. Methods: Anti-MAP-2 antibody, anti-ribosomal P antibody, and IL-6 was measured by ELISA in cerebrospinal fluid with NPSLE patients (n = 24) and non NPSLE patients (n = 18) including viral meningitis or steroid psychosis. Results: Increased autoimmune response against MAP-2 was significantly observed in cerebrospinal fluid with NPSLE patients. Prevalence of anti-MAP-2 antibody was 33.3% (8/24) in NPSLE patients. None of patients with non NPSLE (0/18) reacted with MAP-2. Prevalence of anti-ribosomal P antibody and IL-6 concentration were significantly higher in cerebrospinal fluid of NPSLE patients with anti MAP-2 antibody compared to those of NPSLE patients without anti MAP-2 antibody or those of non NPSLE patients. Conclusion: Anti-MAP-2 antibody in cerebrospinal fluid was recognized in 33.3% patients with NPSLE and it was highly specific for NPSLE. We propose that anti-MAP-2 antibody in cerebrospinal fluid is a novel diagnostic biomarker for NPSLE.

APLAR-0114

Experience on influenza vaccination in SLE patients at UP-PGH ATS HERNANDEZ, ML TEE, AT MAGBITANG, AK GUTIERREZ- RUBIO, AD CORPUZ, KD TEE, JR LIMGENGCO-HIPE Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines Background and Objectives: Systemic Lupus Erythematosus is an autoimmune disease, described as in activity or remission. Various strategies and treatment options are well-recognized for improved patient management and disease control. Vaccination with the influenza and pneumococcal vaccines has been supported in studies worldwide. However, several researches have documented the development of disease flares in patients with autoimmune diseases, and occurrence of a new autoimmune illness in previously healthy subjects, after vaccination. This study therefore aims to report on the experience of influenza and/or pneumococcal vaccinations in Filipino SLE patients at the Philippine General Hospital. Methods : The study was a descriptive study, collected retrospectively through chart reviews done at the Rheumatology Clinic of the Philippine General Hospital. Thirty-one patients were included in the study. Records were reviewed 8 weeks post- vaccination. Adverse reactions were noted. In addition, baseline MEX-SLEDAI was compared to the score 8 weeks post-vaccination. Results: Thirty-one patients were included in this study. All were females. Approximately 80% reported no lupus activity at baseline. Most patients were on multiple drug therapy with lowdose prednisone and an anti- malarial. Eight out of 31 patients had fever, rashes, site irritation, and GI disturbance. Out of the 31 patients, 33% developed an increase in MEX-SLEDAI from baseline, with activity mostly comprising of cutaneous and nephritic manifestations. Non- compliance to medications and sun exposure were the factors identified in the development of flares. Conclusion : Adverse reactions were noted in a small number of patients.Although 33% developed an increase in MEX-SLEDAI from baseline, these increases in baseline activity was noted to be multifactorial and could not be fully attributed to vaccination alone. However, despite such reactions and increases in MEX-SLEDAI, influenza and pneumococcal vaccination still appear to be well * tolerated among SLE patients.

APLAR-0115

Novel autoantibody for SSNA-1 in primary Sjogren syndrome K HIRUMA1, K NOZAWA1, K IKEDA2, A YAMAGUCHI1, I SEKIGAWA2, E CHAN3, Y TAKASAKI1 1

Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 2Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan, 3Department of Oral Biology, University of Florida, Gainesville, American Samua Background: We have previously reported that novel autoantibody against Sjogren’s syndrome nuclear antigen-1 (SSNA-1)/nuclear antigen of 14 kDa (NA14) was often recognized in primary Sjogren syndrome (pSS) patient’s sera. However, the characteristics about the antiSSNA-1 antibody remains poorly understood. Therefore, we conducted this study to clarify characteristics of anti-SSNA-1 antibody about clinical association and mechanism of antiSSNA-1 antibody production.


Materials and Methods: Total 332 sera with various rheumatic diseases including pSS, and with positive reaction for standard autoantigens (SS-A/Ro, centromere, U1-RNP, ds-DNA, Jo1, and nucleolar related proteins) were tested in the present study. Reactivity against recombinant SSNA-1 protein in these sera was evaluated by direct ELISA and immunoblotting. Statistical analysis was performed by paired T test or Chi-square test. Gene expression of SSNA-1, interferon gamma inducible protein of 10 kDa (IP-10), and B cell-activating factor belonging to the TNF family (BAFF) was monitored by quantitative real-time PCR in human salivary cells line (HSG). Serum levels of IP-10 and BAFF were measured by sandwich ELISA. Results: Anti-SSNA-1 antibody was specifically recognized in patients with pSS and mixed connective tissue disease (MCTD). Moreover, increased autoimmune reaction against SSNA-1 was significantly observed in sera with positive reaction against SS-A/Ro, centromere, and U1RNP autoantigens. IIF analysis revealed that anti-SSNA-1 antibody specifically stained only mitotic cells. IFN-c elevated SSNA-1 gene expression to the HSG cells. Serum levels of IP-10 and BAFF were statistically elevated in anti-SSNA-1 positive sera with pSS. Conclusions: In the present study, we identified anti-SSNA-1 antibody as novel mitotic apparatus autoantibody specifically recognized in patients with pSS and MCTD. Excessive IFN-c and abnormal B cells activation play an important role for anti-SSNA-1 antibody production because increased serum levels of IP-10 and BAFF were observed in patients having antiSSNA-1 antibody.

APLAR-0121

Clinical manifestations among juvenile-, adult-, and late-onset SLE D PARK, J LEE, S LEE Rheumatology, Chonnam National University Hospital, Gwangju, Korea Objectives: We have investigated whether SLE patients can be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. Methods: We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing the patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at ≤18 years), adult-onset SLE (ASLE, diagnosed at 19–50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Results: Fever, oral ulcer, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (P < 0.05, P < 0.05, P = 0.001, P < 0.05, and P < 0.05, respectively). On the other hand, Sj*gren’s syndrome was found more frequently in LSLE patients than JSLE or ASLE patients (P < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (P < 0.001). Anti-dsDNA and anti-nucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (P < 0.05, P = 0.005) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (P < 0.001, P < 0.001, and P < 0.05, respectively). Conclusions : Our results showed that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have severe disease activity and more frequent renal involvement and LSLE patients have mild disease activity, more commonly accompanied by Sj*gren’s syndrome.

APLAR-0140

Gene and protein expression profile in SS patients C YONGJING1, S XIAOLIN2, W FANG3, H CIBO3 1

Rheumatology and Immunology Department, Beijing Hospital, Beijing, China, Rheumatology and Immunology Department, People’s Hospital, Peking University, Beijing, China, 3Rheumatology and Immunology Department, Beijing Hospital, Beijing, China 2

Objective : To identify gene expression profile in PBMC of patients with Sjogren’s syndrome (SS) and identify the protein level of these genes screened out, and then analyze correlation between serum protein level and disease activity parameters. Methods: SS patients with leucopenia and three healthy volunteers were included.The cRNA probes prepared for total RNA were hybridized with three identical gene chips.The difference of gene expression of each patient and volunteers were compared. According to statistical analysis and pathway analysis, different expression genes were identified. Serum protein levels of two different expressed genes were detected by ELISA in 40 SS patients, 40 RA patients, 24 OA patients and 40 healthy controls. Independent sample t-test was applied. Correlation analysis was done to investigate the relationship between two serum protein levels and disease activity parameters of SS, including number of white blood cells, organ involvement, ESSDAI score, levels of ESR, CRP, RF, IgG, IgA and IgM. Results: Significant difference in the expression of 82 genes could be detected between patients and volunteers. Among these, 45 were upregulated, and 37 were downregulated. Statistical difierence was calculated between patients and volunteers especially in the following two pathways: the complement and coagulation pathways (including C2, PROS1, F2R and SEPPING1) and the cytokine-cytokine receptor interaction pathway (including FASLG, MPL, CCL20 and CXCL2) (P < 0.01). Further study identified that CXCL2, CCL20 levels were significantly higher in SS patients than in healthy controls (P < 0.01). CCL20 level was significantly correlated with number of white blood cells and level of CRP, while negatively with pulmonary interstitial diseases, positive correlation was observed between CXCL2 level and number of white blood cells. Conclusion : This study has identified distinct gene expression profiles in PBMC from patients with SS patients with hematology involvement and healthy volunteers. Among which, CXCL2 and CCL20 play a part in the development of SS and their determination may benefit evaluation of disease activity.

65


APLAR-0165

PD-1 deficient Th1 cells induced systemic inflammation M TAHARA1, Y KONDO1, M YOKOSAWA1, H TSUBOI1, S TAKAHASHI2, I MATSUMOTO1, T SUMIDA1 1 Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki Tsukuba, Japan, 2Departments of Anatomy and Embryology, Faculty of Medicine and Laboratory Animal Resource Center, University of Tsukuba, Ibaraki Tsukuba, Japan

Objective: To clarify the role of programmed cell death-1 (PD-1) in the differentiation and the function of Th1 cells. Methods: (1) We generated PD-1 deficient T-bet Tg (P/T) mice by crossing T cells specific Tbet transgenic (T-bet Tg) mice with PD-1 knock-out (PD-1 KO) mice, and assessed the phenotype of P/T mice. (2) Histological analyses were performed in heart, spleen, lung, liver, pancreas, kidney, salivary gland, lachrymal gland, intestine and ear skin from wild-type mice (WT), PD-1 KO mice, T-bet Tg mice, P/T mice with H&E staining and immunofluorescence staining. (3) CD4+ T cells isolated from spleen were stimulated with anti-CD3/CD28 monoclonal antibodies, and cytokine production and transcription factor expression were analyzed by FACS. (4) Total splenocytes or splenic CD4+ CD25 T (Teff) cells from P/T mice were transferred into Rag-2 KO mice, and then the phenotypes and histological changes were evaluated.

Objective: Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. Methods: A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000-January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. Results: The PLE group had lower mean serum albumin and 24-h urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (150 mg/dL (P < 0.05), LDL >130 mg/dL (P < 0.05) and HDL >40 mg/dL (P < 0.05). Hypertension was significantly with associated with total cholesterol of >200 mg/dL (P < 0.05), triglyceride >150 mg/dL (P < 0.05). By logistic regression, MEX-SLEDAI score of ≥7 was a significant predictor of dyslipidemia showing 10 times risk compared to patients with a MEX-SLEDAI score of 0.05). Associations of Ets-1 and FOXP3 mRNA expression levels with major clinical and laboratory parameters of SLE patients were also analyzed. However, no significant association was found. Significant positive correlation was found between Ets-1 and FOXP3 mRNA expression in CD4+CD25+ Treg cells from SLE patients (r = 0.698, P < 0.001). Conclusions: Our results found that the expression levels of Ets-1 mRNA were decreased in SLE patients and Ets-1 expression was positively correlated with the expression of FOXP3. It indicated that Ets-1 may play an important role in the stable expression of FOXP3 in CD4+CD25+ Treg cells.


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APLAR-0424

Pregnancy outcomes among Filipino SLE patients C TAN, STV NAVARRA Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Background: Pregnancy poses a relevant management challenge in systemic lupus erythematosus (SLE), a disease which usually affects women of child-bearing age. Objectives and Methods: We retrospectively reviewed the maternal and fetal outcomes of SLE patients included in the SLE database of the UST Hospital.


APLAR-0434

Neuropsychiatric involvement in Filipino SLE patients MT SALVADOR, S NAVARRA Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Background and Objective: Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) include headache, seizure, cognitive or behavioral changes, cranial or peripheral neuropathy.The underlying etiology is not always attributable to SLE disease activity and can be secondary to central nervous system (CNS) infection or drug adverse effects.This study describes the various etiologies for neuropsychiatric manifestations among Filipinos with SLE. Methods: Retrospective study of patients confined at the University of Santo Tomas Hospital in Manila, Philippines from November 2008 to October 2013 for acute neuropsychiatric manifestations. We reviewed the medical records for the features and causes of neuropsychiatric involvement, SLE disease characteristics, and co-morbidities such as antiphospholipid syndrome. Results: A total of 35 patients (34 females) with average age 28 9.1 years old and mean SLE disease duration of 5.38 3.63 years were included in this study. Mean prednisone dose was 12.5 8.7 mg/day. Overall, 11 presented with behavioral changes (31%), 10 withsevere headache plus fever (28%), 6 patients each with seizure and cranial nerve deficit (17%), and 2 with lupus headache alone (5.7%). There were 11 patients diagnosed with CNS infection (10 tuberculous meningitis, 1 bacterial meningitis), while 3 patients were receiving acyclovir for herpes zoster prior to onset of neuropsychiatric symptoms, with resolution of symptoms upon discontinuation of the antiviral. Five withantiphospholipid antibodies presented with cranial nerve deficit (3 patients), seizure and behavioural change in 1 patient each. The 21 patients with primary neuropsychiatric SLE (NPSLE) received pulse methylprednisolone with2 patients continuing to complete 6 months cyclophosphamide pulse regimen. There were a total of 11 deaths (31%), 6 of whom had CNS infection. Conclusion: In this series, nearly half of patients with neuropsychiatric manifestations had etiologies other than SLE. It is crucial to recognize secondary causes such as infection and drug effects, as specific treatments like antimicrobials or drug discontinuation determine favourable outcomes in these situations. Funding: Lupus-Inspired Advocacy (LUISA) Project of Rheumatology Educational Trust Fund Inc. (RETFI)

APLAR-0435

Flare assessment by PGA and incomplete disease activity measures L ZAMORA, MT SALVADOR, SV NAVARRA Medicine, Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Background and Objective: SLE disease activity assessments utilizing SELENA-SLEDAI and MEX-SLEDAI instruments require laboratory tests which are not affordable by many patients in developing countries. This study explores the concordance of incomplete SELENA-SLEDAI and MEX-SLEDAI instruments on physician global assessment (PGA) scores among Filipino SLE patients consecutively seen at a tertiary care facility. Methods: Disease activity assessments were conducted among Filipino patients consecutively being seen at the Lupus clinics at University of Santo Tomas (UST) Hospital from May 2013 to October 2013. Each patient was assessed using incomplete SELENA-SLEDAI (without immunologic tests), incomplete MEX-SLEDAI (without creatinine), and PGA. An independent assessor determined the presence or absence of flare by SLE Flare Index (SFI).Concordance among these measurements was assessed by Chi-square analysis. Results: A total of 113 patients (107 females) with average age 33.9 10.7 years old and mean SLE disease duration of 9.24 16.1 years were included in this study. SLE disease flare was present in 43 (38%) patients, 32 of which were categorized as mild to moderate and 11 as severe flares. Concordance in PGA, incomplete SELENA-SLEDAI and MEX-SLEDAI assessments were greatest among patients with severe flare or those with clinically quiescent disease; there was less concordance among those with mild to moderate flare. Conclusion : This study showed a 38% occurrence of disease flare in this cohort. Further analyses also suggest that missing certain laboratory information from standard disease activity instruments did not significantly impact clinical assessment * and may not be necessary to perform * among certain groups of patients. A larger cohort and longer-term observational studies are recommended to substantiate these findings. Funding: Lupus-Inspired Advocacy (LUISA) Project of Rheumatology Educational Trust Foundation Inc. (RETFI)

APLAR-0444

End-organ damage in a cohort of Filipino lupus patients CL MACAPAGAL, SV NAVARRA Rheumatology Clinical Immunology and Osteoporosis, University of Santo Tomas Hospital, Metro Manila, Philippines Objective: This study describes the prevalence and characteristics of end-organ damage in a cohort of Filipino systemic lupus erythematosus (SLE) patients at a tertiary hospital. Design: This retrospective study reviewed the medical records of adult (≥18 years old) patients seen at the lupus clinics of University of Santo Tomas Hospital from January 1, 2011

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to December 1, 2013. Patients with incomplete charts and who were lost to follow-up for at least 6 months were excluded. Patients were assessed for the presence of end-organ damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/SDI). Presenting manifestations at diagnosis, average steroid dose per day and cyclophosphamide use were also analyzed. Results: 295 patients (281, 95% females), with mean age at diagnosis at 29 10.7 years and mean disease duration of 9 5.6 years were included in the study. 172 (58.3%) had at least 1 end-organ damage. The most commonly damaged organ systems were the renal (85, 49%), neuropsychiatric (35, 20%), ocular (34, 20%), and musculoskeletal (32, 19%). Damage occurred at an average of 4 years after diagnosis. Development of a subsequent damage occurred at an average of 1 year after the first damage. Among those with end-organ damage, mucocutaneous, musculoskeletal, and renal were most common presenting manifestations. Seventy three (42%) of these patients had received cyclophosphamide at any time and average steroid dose was 11 mg of prednisone or equivalent per day. Conclusion: In this cohort of SLE patients, more than half had at least 1 end-organ damage. The renal, neuropsychiatric, ocular, and musculoskeletal were the most damaged organ systems. Mucocutaneous, musculoskeletal, and renal were most common presenting manifestations at SLE diagnosis. Funding: Lupus Inspired Advocacy (LUISA) of Rheumatology Educational Trust Foundation, Inc.

APLAR-0446

Survival in Filipino male SLE patients may be linked to renal disease M SAQUING, S TUPAS, SV NAVARRA Medicine, University of Santo Tomas, Metro Manila, Philippines Objective: To compare the organ involvement and survival of Filipino males vs. females with systemic lupus erythematosus (SLE). Methods: Retrospective study comparing demographics and presenting clinical and laboratory manifestations by ACR classification criteria and survival of Filipino male vs. female lupus patients included in the lupus database of the University of Santo Tomas (UST) Hospital, Philippines from 1998 to 2012. Results: A total of 1470 patients entered in the UST Lupus Database included 1375 (94%) females and 95 (6.46%) males. Average age at diagnosis was 28.47 11.65 years. Average disease duration was 63 75.08 months in males vs. 99 75.66 months in females. Renal involvement and hematologic manifestations were more common (58% vs 41%, P < 0.0008) and (55% vs 42%, P < 0.0139) respectively in males whereas arthritis (58% male vs 71% females, P = 0.0152) and photosensitivity (38% males vs 52% females, P = 0.0150) were more common in females. Overall 15 year survival was 85% (female:85%; male:79%) with standardized mortality ratio (SMR) of 25.76. Of the 22 male (23%) who died, the average disease duration was 48 46 (range 1–202) with renal failure (27%) and infection (27%) as the primary causes of death. Conclusion : Renal and hematologic manifestations were more common in males than females, whereas the more symptomatic musculoskeletal and cutaneous ie photosensitivity manifestations were more common in females * reinforcing the need for earlier detection and aggressive management of renal involvement especially in males with SLE. Poorer survival also appeared to be linked with renal involvement in this group of Filipino male SLE patients. Funding: Lupus inspired advocacy (LUISA) Rheumatology Educational Trust Foundation, Inc.

APLAR-0460

Serum level of 25-hydroxyvitamin D3 in newly onset SLE patients O JIN, HY HUANG, X ZHANG, ZM LIN, DF LIN, LK FANG, CC HOU, ZT LIAO, ML QIU, JR GU Department of Rheumatology, Affiliated 3rd Hospital of Sun Yat-san University, Guangzhou, China Objectives: Vitamin D deficiency has been found in SLE patients, however, whether this deficiency is due to SLE intrinsic abnormality or a result of some other reasons are still not clear. We aim to investigate the serum 25(OH)D3 levels on newly diagnosed SLE patients, and its relationship between the bone degradation marker ICTP or SLE disease activity index (SLEDAI). Methods: Forty-four SLE patients were divided into three groups: (1) newly onset SLE (2) avtive SLE (3) stable SLE. Age and sex matched healthy donor were recruited. Both group 2 and 3 patients were given Vitamin D and Calcium to avoid GIOP. Serum levels of 25(OH)D3 and ICTP were measure by ELISA. Results: (1) The level of 25(OH)D3 in newly on-set SLE patients (32.75 3.20 nmol/L) was significantly lower than active (60.50 7.21 nmol/L) or stable (59.23 5.06 nmol/L) SLE and healthy donors (60.97 4.89 nmol/L) (P < 0.05, respectively), while there were no differences between active, stable SLE patients and the healthy donors. No correlation was found between the level of 25-vitamin D and ICTP, or SLEDAI. (2) The level of ICTP in newly on-set (13.05 3.00 lg/L) and active SLE (9.23 2.59 lg/L) was significantly higher than stable SLE patients (5.13 1.14 lg/L, P = 0.009). The levels of ICTP were correlated with SLEDAI in newly on-set (r = 0.70, P = 0.016), active (r = 0.83, P = 0.001) and stable (r = 0.59, P = 0.005) SLE. Conclusions: 1. The low level of 25(OH)D3 in newly on-set SLE patients suggests that this may be an intrinsic abnormality, which may contribute to the pathogenesis of SLE. After treat with Vitamin D and Calcium, both active or stable SLE reached normal 25(OH)D3 level. 2. The level of ICTP in newly on-set and active SLE patient was significantly higher than stable SLE patients, and was correlated with SLEDAI, suggesting that the inflammation of SLE may influence the bone degradation.



APLAR-0474

APLAR-0489

Serum levels of osteopontin and matrix metalloproteinase-3 in SLE

Long term outcome of systemic lupus erythematosus in Iran

O JIN1, X ZHANG1, A CHAN2,3, T MOK2,3, HY HUANG1, CC HOU1, JR GU1, CS LAU2,3

A FATEMI1, M MATINFAR2, MR MARACY3, Z SAYEDBONAKDAR1, M SABER4, A SMILEY5

1

1 Rheumatology, Isfahan University of Medical Sciences, Isfahan, Iran, 2Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran, 3School of Health, Isfahan University of Medical Sciences, Isfahan, Iran, 4Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran, 5Epidemiology, Poursina Hakim Research Center, Isfahan, Iran

Department of Rheumatology, Affiliated 3rd Hospital of Sun Yat-san University, Guangzhou, China, 2Department of Rheumatology, The University of Hong Kong, Hong Kong, China, 3Department of Medicine The University of Hong Kong, Hong Kong, China Introduction: Osteopontin (OPN) has been suggested to contribute to renal injury through its ability to enhance chemotaxis. This, and the discovery that OPN is a substrate for matrix metalloproteinase-3 (MMP-3), the expression of both of which have been shown to be increased in experimental lupus mice led us to investigate their roles in SLE. Method: Serum levels of OPN and MMP-3 were measured by ELISA. Five groups of subjects were studied: Group 1: healthy controls; Group 2: SLE patients with SLE disease activity index (SLEDAI) ³4; Group 3: SLE patients with SLEDAI < 4; Group 4: SLE patients with a past history of renal disease; Group 5: SLE patients with no history of renal disease. Results: Patients with SLE had higher serum levels of OPN and MMP-3 than controls. Those with a past history of renal disease had the highest OPN levels (versus Group3, P < 0.01; versus Group 5, P < 0.001). Serum levels of MMP-3 were significantly elevated in patients with active disease (versus Group 3, P < 0.001) and previous renal complications (versus Groups 3 and 5, both P < 0.05). Serum levels of OPN correlated significantly with those of MMP-3 (r = 0.46, P < 0.01, n = 93). Conclusion: The highest serum levels of OPN observed in patients with renal disease suggests OPN may have a pathogen role in SLE renal injury. Increased serum levels of MMP-3 in SLE patients with active or renal disease, and their positive correlation with those of OPN confirmed the regulatory role of MMP-3 in OPN bioactivity, as well as its possible role in lupus nephritis.

Introduction: There are little data on mortality of systemic lupus erythematosus (SLE) patients and its predictors in Iran. Method: In a retrospective study, 394 adult patients with a diagnosis of SLE according to ACR criteria who admitted to the university hospital between 1985 and 2011 were included in the study. The demographic, clinical and paraclinical data were extracted at the time of diagnosis. SLE disease activity index (SLEDAI) was calculated. The current health status of patients was tracked by reviewing their files or by phone call, if they did not have regular follow-up. The cause of death was recorded. Predictors of SLE mortality were computed by Cox regression analysis. Results: 352 (89.3%) patients were female. 35 patients (8.3%) died during the study period. The causes of death were circulatory (13/35), infectious (10/35) and renal (10/35) problems. The mean (SE) survival time and the 95%CI were 21.6 (0.66) and 20.4–23 years, respectively. The overall cumulative rate of survival (SE) at the end of 5, 10, 15, 20 and 25 years after SLE disease diagnosis was 93 (1), 90 (2), 90 (2), 80 (6) and 62 (12) percent, respectively. With univariate analysis, age of onset ≥35 years, seizure, hematuria, pericarditis or SLEDAI ≥20 at the time SLE diagnosis had significantly poorer survival. By adjustment for sex, the following variables showed no more significant association with survival of patients: seizure, hematuria and SLEDAI ≥20. Conclusion: The overall SLE survival rates in Iran were comparable to those in developed countries. Patients with pericarditis who aged 35 years or older had the lowest survival rates.

APLAR-0500

Effect of vitamin D on endothelial damage initiated by Neutrophil Extracellular Traps (NETs) formation of Systemic Lupus Erythematosus (SLE) patients APLAR-0485

Program therapy of SLE

K HANDONO1, BA PRADANA2, IA HARTONO2, RA NUGROHO2, Y SIDARTA2, AT ENDHARTI3, H KALIM4

N OMURZAKOVA

1

Rheumatology, National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyz Republic Objectives: To develop the optimum scheme of intensive therapy for treatment of patients with SLE. Materials and Methods: 52 patients are included in the research (average age 27.2 5.7 years) with various forms of SLE with high activity of process, resistant to standard steroidal therapies. Results: At heavy forms of SLE intensive therapy by methylprednisolone (MP) was spent in the form of classical 3 day time pulse therapy with addition of cyclophosphan for 2-nd day, at the rate of 15–20 mg/kg (1000 mg/1 square m. surfaces) and Hydroxychloroquine (Plaquenil) 200 mg per day. Carrying out of the combined intensive therapy (MP and cyclophosphan) had a positive effect at system damages of lungs and kidneys. Most effectively early beginning of treatment because of high risk of development of irreversible necrotizing defeats of the vital part of bodies, first of all kidneys. Further program application of methyl prednisolone pulse therapy (MPPT) in a combination with cyclophosphan was conducted with an interval of 1 time within 2 weeks, then 1 time within 4 weeks during 12 months. After 1 year 32 patients were treated by cyclosporine + Plaquenil, 8 patients by azathioprine + Plaquenil, 5 died after mixt infection. Conclusions: System purpose of having the MP inside was an obligatory component of treatment of patients with SLE in a doze of 20–30 mg/day. Application of greater dozes is justified at heavy development of diseases at patients with development of multiple organ failure. Using of Plaquenil shows favourable results.

Department of Clinical Pathology, Brawijaya University, Malang, Indonesia, Department of Biomedical Science, Brawijaya University, Malang, Indonesia, 3 Department of Parasitology, Brawijaya University, Malang, Indonesia, 4Department of Internal Medicine, Faculty of Medicine, Brawijaya University 2

Background: It has been suggested that a subset of abnormal neutrophils has an important role in the pathogenesis of SLE through increased Neutrophil Extracellular Traps (NETs) formation and endothelial cells damage. Vitamin D deficiency has been reported to be correlated with the pathogenesis of SLE. The aim of our study was to know whether the effect of vitamin D treatment on endothelial apoptosis was mediated by abnormal NETs formation. Methods: Neutrophils was isolated from newly diagnosed SLE patients blood with moderate disease activity (SLEDAI 13 2.4). The purity of neutrophils (70%) was determined with a CyFlow Space flow cytometer (Partec) using staining with anti-CD16. To assess the effect of vitamin D, the neutrophils were cultured in RPMI-1640 medium and treated with different doses of 1,25(OH)2D3 (10–7, 10–8, 10–9 mol/L) and without vitamin D (control) and stimulated to induce NETs using 20 nmol/L PMA. The supernatant (NETs) was separated and cocultured with HUVECs. NETs formation was assessed by the externalization of NETs constituents: myeloperoxidase (MPO) and histones. MPO was measured by ELISA, histones by immunoflorescen stanning. Early and late apoptosis of endothelial cell was measured by flowcytometry using cell death kit (annexin V and PI antibody). We analyzed the NETs formation and the percentage of endothelial cells apoptosis between each group of vitamin D treatment. Result : Our study showed that NETosis (number of cells externalizing histones) was lower in neutrophils treated with vitamin D (28.26 5.4; 14.15 8.28; 18.35 5.74) compared with control group (52.16 24.6), P = 0.012. However, there was no significantly different between each group with different dose of vitamin D. The percentage of endothelial cells apoptosis was not significantly different between groups of vitamin D treated and untreated. Conclusion: Vitamin D may decrease number of neutrophil cells which externalized histones, but was not able to inhibit endothelial cell death. Keywords: SLE, NETs, MPO, Histone, Vitamin D, Apoptosis


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APLAR-0225

The effect of tonsillectomy on pustulosis palmaris et plantaris A ITO1, Y MASUI1, T ITO2, M ITO1 1 Dermatology, Niigata University, Niigata, Japan, 2Orthopaedic surgery, Niigata General Hospital, Niigata, Japan

Background: Pustulosis palmaris et plantaris (PPP) is considered to be an associated disease of psoriasis, however, in Japan we treat PPP as an independent disease from psoriasis. PPP is resistance to medical treatments such as steroid ointment, vitamin D3 ointment, vitamin A, cyclosporine, or ultraviolet treatment. Our strategy to treat PPP is cause-based treatment. At first we perform the examinations such as checking dental focal infection, provocation tests of tonsillitis, and the patch test of metal allergy, and eliminate causes. To the patients who smoke, we recommended quitting smoking.

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Objective: In this study, we examine the effect of tonsillectomy for arthritis, nail deformity and skin eruption in PPP patients. Materials and Methods: This retrospective study included 24 cases diagnosed as PPP by skin symptoms and received tonsillectomy in our hospital from 2000 to 2010. We reviewed the charts and images retrospectively. There were 10 (42%) males, and 14 (58%) females. The ~ mean age was 42.75 years while the oldest was 65 and the youngest was 20 years patientsO old. Six patients had arthritis, and nine had nail deformities. The smoking rate was 71% (male; 70%, female; 71%). Results: Following tonsillectomy, the skin eruption improved in 19 out of 24 patients (79.2%). In five out of six who had arthritis, their joint symptoms had improved, and in seven out of nine, their nail changes had improved. Positive rate of provocation test was 42% (10 of 24), and following tonsillectomy, nine of 10 (90%) patients improved their skin eruption. Negative rate was 58% (14 of 24), eight of 14 (57%) patients showed completely recovery and in three patients, their symptoms were significantly reduced. Conclusion: According to the results of this study, a tonsillectomy can be considered as a treatment modality for PPP irrespective of the results of provocation test.


Clinical Rheumatology – T08: Spondylarthropathies – clinical aspects and co-morbidity

POSTER SESSION II ABSTRACTS Clinical Rheumatology – T08: Spondylarthropathies – clinical aspects and co-morbidity

APLAR-0166

A multi-center genetic epidemiological study for AS Z LIN, Z LIAO, OU JIN, M YANG, D LIN, J GU Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objectives: We conducted a multi-center genetic epidemiological study to detect the risk factors and familial risk of ankylosing spondylitis. Subjects and Methods: We enrolled AS patients from 10 centers. We investigate the patients’ information by questionnaires face to face. We collected patients’ clinical features including disease type, hip joint involvement, dactylitis, peripheral arthritis, iris, inflammatory back pain, onset symptom (axial symptom and peripheral symptom) and family history. Result: 2039 patients enrolled in this study were shown as follows: mean age was 27.32 8.90 years; mean age of onset was 20.71 7.15 years; male to female ratio was 4.07:1; 420 (20.60%) patients had positive family history. Irits (162/2039, 7.95%), dactylitis (94/2039, 4.61%), hip joint involvement (636/2039, 31.20%) occurred. 1102 (54.05%) patients had both axial and peripheral symptoms. The onset symptom in 851 (41.74%) patients was peripheral manifestaion. 170 patients’ (8.34%) parent(s) was affected. (2)?Male affect probands’ onsetage were significantly earlier than female ones (P = 0.000). ?The onset age of probands (n = 167) whose parent(s) was affected was significantly younger than ones whose parent(s) was normal 18.70 5.46 y/20.88 7.23 y, P = 0.001). ?Among female probands, the percentage of first-borrn of probands whose parent(s) was affected was more than ones whose parent(s) was normal (58.06%:38.27%, P = 0.031). ?Hip involvement was significantly more frequent in probands whose parent(s) was affected than ones whose parent(s) was normal (43.71%:30.07%, P = 0.000). ?However, no significant different factors was detected between the probands whose mother was affected and ones whose father was affected. Conclusion: Male affect probands’ onsetage were significantly earlier than female ones. The onset age of probands whose parent(s) was affected was significantly younger than ones whose parent(s) was normal. And parent(s)’s affection was a risk for hip involvement in ankylosing spondylitis. Parent(s)’s affection is a risk factor for first-born female.

Objectives: To compare clinical features of patients with ankylosing spondylitis (AS) from the south and north China, and to find out whether these differences have an impact on the course of disease. Methods: We collected information of 1079 patients with AS and grouped them by their birthplace. Patients, who born in the south of Qinling-Huaihe River were classified as the south group, and the others were classified as the north group. We investigated for their clinical features, including the age of disease onset, duration, axial and peripheral joints involvement, extra-articular manifestations, family history, social habits, and treatments. Results : 578 patients were from the south and 501 were from the north. The age, sex, age of disease onset, duration, and family history between two groups were of no differences (all P > 0.05). In the south group, more patients had axial joints arthritis initially. Whereas, in the north group, more patients had peripheral joints initially (both P < 0.05). Extra-articular manifestations like uveitis and sausage digits were more often to be seen in the north group (both P < 0.05). More patients of the north group had a smoking habit (43.5% vs. 39.3%, P < 0.05), while more south patients had a drinking habit (57.1% vs. 48.1%, P < 0.05). Treatments were also different between two groups. Traditional Chinese medicine (52.9% vs. 45.0%) and sulfasalazine (48.9% vs. 28.5%) were more often to be used in patients from the north group than from the south group (both P < 0.05). But the use of NSAIDs (42.2% vs. 38.7%, P < 0.05) was more often in the north group. And the usage of biological agents were similar between two groups (9.2% vs. 9.4%, P > 0.05). Conclusions: There were some differences of clinical features between the AS patients from the south and north China, and these differences may have some impacts on the course of disease.

APLAR-0317

Uveitis do not correlate with other clinical features in AS patients ZY HU, Q LV, ZM LIN, MC YANG, J QI, JR GU Department of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

APLAR-0204

Clinic features, linkage studies of SNPs in an AS family with HLA-B2715

Objectives: To compare the specific clinical features in ankylosing spondylitis (AS) patients with or without uveitis, and to find out whether uveitis correlate with other clinical features.

Y LI, Y MOU, P ZHANG, Z LIAO, Z LIN, J GU

Methods: We collected information of 649 patients with AS and grouped them by having uveitis or not. We investigated these AS patients for their clinical features, including the age of disease onset, disease duration, first related joints, axial and peripheral joints involvement, family history, social habits, and treatments. Results : 299 AS patients were in the uveitis group and 350 were in the non-uveitis group. The sex, age of disease onset, family history, drinking and smoking habit between these two groups were of no significant differences (all P > 0.05). Patients of the uveitis group were younger than the non-uveitis group (30.9 9.8 vs. 27.2 8.9 years old, P < 0.05) and had a longer disease duration (9.6 8.1 vs. 6.3 6.1 years, P < 0.05). Patients of the uveitis group were more often to have the axial joints involved initially than the peripheral joints (72.9% vs. 52.8%, P < 0.05), but the patients of the non-uveitis group do not have this incline (P > 0.05). And the uveitis group had more cervical and thoracic spine affected, while the non-uveitis group had more sacroiliac joints and lumbar spine involvement (all P < 0.05). The use of drugs was also different between two groups. Non-steroidal anti-inflammatory drugs (86.8% vs. 73.2%) and biological agents (12.0% vs. 3.4%) were more often to be used in patients from the uveitis group (both P < 0.05). But the use of traditional Chinese medicine, sulfasalazine and glucocorticoid were similar between two groups (all P > 0.05). Uveitis do not correlate with other clinical features as mentioned above (all P > 0.05). Conclusions: We concluded some features of the AS patients with uveitis, and find out that uveitis do not correlate with other clinical features.

Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Background: HLA-B*2715 is a rare subtype found in Asia. It is helpful to investigate the clinical datas, SNPs and cytokines in a family carrying B*2715 for understanding the association of B*2715 with ankylosing spondylitis (AS) . Objective: To study an AS family carrying HLA-B*2715 by analyzing subtypes of B27 and clinical datas, genotyping of B*2715 for SNP and. detecting serum levels of MMP-3, sRANKL and OPG. Methods: A total of 14 members belonged to the AS family were included. B27 Typing was performed by Lumina liquid array combining PCR-SSOP method. HLA-B27 subtyping was performed by PCR-SSP. The sequence-based typing was performed for the B*2715 samples. A total of 7 family members carrying B*2715 were genotyped on Illumina Infinium arrays using HumanHap 610-quad chip, which contains 620901 SNPs. Serum levels of MMP-3, sRANKL and OPG was performed by ELISA . Results: Fourteen members were collected in the AS family and seven of them carrying B*2715. Six AS patients were found in adult members carrying B*2715 except a child. There were no significant differences for levels of MMP-3, sRANKL and OPG between members carrying B*2715 and those B*2715 negative (P > 0.05) and there were no significant differences for levels of MMP-3, sRANKL and OPG between six AS patients carrying B*2715 and six B*2715 negative family members (P > 0.05). One SNP was found in B*2715 gene of patients in the family,. of which LOD value was 0.7996. Conclusion: The morbidity of AS in family carrying B*2715 allele was high, these results show that B*2715 may be disease-association subtype. LOD value of SNP for 0.05). Conclusion : The levels of sCD30 in AS cases were highly increased compared with normal controls. Being a typical indicator of T cell activation, sCD30 may play important roles in the pathogenesis of AS through regulating T cell functions, which might become a new diagnostic and therapeutic target in the future. Attributed to the limitation of sample numbers and the subjectivity from patients and doctors, a large number of samples’ study is in urgently need to deeply investigate the precise roles of sCD30 in pathogenesis of AS and the relationship among sCD30 and other indexes indicating the severity of disease.

APLAR-0363

Abnormality of VitD and ICTP in patients with ankylosing spondylitis P ZHANG, Z LIN, Z LIAO, OU JIN, L FANG, J GU Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton. The decreasing of vit D level in AS has been reported to be associated with high disease activity and Osteopenia.The pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP), a sensitive indicator of bone resorption, can reflect the level of bone turnover, but few study has reported its relationship with pathological bone destruction in AS. Objectives: To identify the serum vitamin D and ICTP levels in AS patients, to assess their correlations with disease activity and bone mineral density (BMD). Methods: 150 AS patients and 168 controls were included in this study, their ages were from 13 years old to 50. Serum 25(OH)D and ICTP were detected in patients and controls, while Edimentation rate (ESR), C-reaction protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Hip BMD T-score were assessed only in patients. The multiple linear regression model analysis was performed to assess the contribution of clinical parameters to the BMD. Results: The serum 25(OH)D was significantly lower and ICTP was higher in AS than in controls (P < 0.05). ICTP was found higher in men than in women with AS, and it was higher in patients under 18 years old than that above 18. By multiple linear regression model analysis, we found that ICTP, BASDAI, Disease duration and 25(OH)D all contributed to the low hip BMD T-score. 25(OH)D was negatively correlated with ICTP. However, no obvious correlation between 25(OH)D and disease activity index was found, although there was a significant relationship between CRP, ESR, BASFI and serum ICTP level.

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Conclusion: There was a high incidence of vitD inadequacy in AS, while serum ICTP level was elevated in them, especially in young and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS.

APLAR-0440

Psychological disturbance affect subjective scoring in AS patient M YANG, Z LIN, Y JIANG, Z LIAO, Z HU, J GU Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Background: Our previous research showed that patients with ankylosing spondylitis (AS) had more psychological disorders than healthy controls, including anxiety, depression and sleep disturbance. And these disorders were associated with patient global pain score, BASDAI, BASFI and healthy accessing index, etc. Objective: To investigate whether psychological disturbance could influence subjective disease scoring in AS patients independently, especially in addition to the disease inflammatory indexes. Method: We re-evaluated scores of self-administration questionnaires, including BASDAI, BASFI, HAQ, Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), and also ESR and CRP of 683 AS patients in previous study. The severity of anxiety and depression was graded into 0–3 based on SAS and SDS scores individually. In order to accomplish linear association, we took the square root of ESR and Ln (CRP +1) natural logarithm processing referring to ASDAS formula. The clinical indexes between patients with different SAS and SDS scores were compared by using ANOVA. Result: Number of subject with SDS grading from 0 to 3 was 246, 302, 107 and 28, respectively. There were significance differences in BASDAI, BASFI and HAQ-S among each subgroup, while no difference was detected in ESR and CRP. Number subject with SAS grading from 0 to 3 was 471, 157, 43 and 12, respectiely. Similarly significance differences were found in BASDAI, BASFI and HAQ-S, but we still did not discover differences in ESR and CRP among different subgroups. Conclusion: The AS patients with different anxiety and depression status have corresponding different self-accessing scores, as well as similar inflammation index levels. This finding might imply that psychological status could be an independent factor affecting patient’s self-accessing on their diseases. Therefore, psychological Intervention should be part of necessary treatments rather than optional consideration accompanied by medication in AS patients.

APLAR-0454

Two-year follow-up for patients with chronic back pain ≥3 months Z LIN, P ZHANG, Z LIAO, Z HU, L FANG, S CAO, Q WEI, J GU Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: To evaluate the ASAS classification criteria for axial SpA in distinguishing Chinese axial SpA patients from other back pain patients in a 2-year follow-up study. Methods: Patients with chronic back pain ≥3 months and age at onset before 45 were enrolled and classified as axial SpA or non-SpA according to ESSG criteria, Amor criteria or ASAS classification criteria for axial SpA, respectively. Final diagnosis of axial SpA and non-SpA were confirmed by rheumatologists after 2-year follow-up. Sensitivity and specificity of each SpA parameter was calculated basing on final diagnosis. Diagnosing coincidence with the final diagnosis of ESSG criteria, Amor criteria and ASAS axial SpA classification criteria were evaluated. Result: Eight hundred and sixty-seven patients with chronic back pain were enrolled and completed the 2-year follow-up. They were diagnosed as 455 axial SpA patients and 412 non-SpA patients after 2-year follow-up. In the first visit, the ASAS criteria could distinguish more SpA patients (n = 407) than ESSG criteria (n = 371) and Amor criteria (n = 399), and more nonSpA patients (n = 356) than ESSG criteria (n = 320) and Amor criteria (n = 316). After verified by follow-up, the classification coincidence of ASAS criteria (Kappa = 0.7593) was better than ESSG (Kappa = 0.5926) and Amor criteria (Kappa = 0.6469) in the chi-square test. Sacroiliitis on MRI had extremely high value to classify SpA patients from patients with chronic back pain (Axial SpA group & non-SpA:80.98% & 3.63%, P ≤ 0.001) Conclusions : ASAS axial SpA classification criteria were superior to ESSG criteria and Amor criteria in clinical practice to diagnose axial SpA patients in China.

APLAR-0466

High disease activity in spondyloarthropathies in NE India P SARMA1, A MAHANTA2, B CHAKRABORTY2 1 Rheumatology, Excel Centre, Guwahati, India, 2Medicine, Gauhati Medical College, Guwahati, India

Aim: There is a paucity of data on spondyloarthropathies from the North-Eastern part of India which comprises of people of diverse ethnic origins quite distinct from the rest of the Indian population. This study was undertaken to see the clinical profile of spondyloarthropathies in North Eastern India. Materials and Methods: Patients fulfilling Assessment of Spondyloarthritis International Society (ASAS) 2009 criteria for axial Spondyloarthropathy who attended the Medicine O.P.D at


Clinical Rheumatology – T08: Spondylarthropathies – clinical aspects and co-morbidity

Gauhati Medical College and Hospital from July 2011 to June 2012 were included in the study. Results: Ankylosing Spondylitis was the most common type of spondyloarthropathy (40.95%) followed by undifferentiated spondyloarthropathy (32.38%) among the 95 study patients. Median age of onset and presentation was 25 years and 30 years respectively.The peripheral joints were involved predominantly in the lower extremity (knee = 53.3%, ankle = 49.1%) while wrist (20.95%) was the most frequently involved joint in the upper extremity. Heel (59.04%) was the most common site of enthesitis followed by the tibial tubercles (40.95%).The mean BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score in Ankylosing Spondylitis, Reactive Arthritis, Psoriatic Arthritis, Juvenile Spondyloarthropathy and Undifferentiated Spondyloarthropathy was 4.8 2.4, 5.1 2.2, 5.2 2.1, 5 2.3 and 5.1 2.2 respectively. The mean BASFI (Bath Ankylosing Spondylitis Functionnal Index) score in Ankylosing Spondylitis, Reactive Arthritis, Psoriatic Arthritis, Juvenile Spondyloarthropathy and Undifferentiated Spondyloarthropathy was 4.9 2.7, 4.5 2.5, 5.1 2.6, 4.4 1.9 and 4.2 2.5 respectively. Sacroiliitis on imaging was found in 74.41%, 23.52%, 28.57% and 52.94% of cases in ankylosing spondylitis, Reactive arthritis, Psoriatic Arthritis and Undifferentiated Spondyloarthropathy respectively. The association of HLA B-27 with Ankylosing spondylitis, Reactive arthritis and Undifferentiated Spondyloarthropathy was found to be 74.41%, 58.82% and 67.65% respectively. Conclusion : In this study we found that Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy were the most common spondyloarthropathies. Despite a median duration of disease of 5 years the study patients had high BASDAI & BASFAI scores reflecting poor disease control.

Methods: This study included 470 patients with AS. Direct sequencing was used to identify the HLA-B27 genotype. Clinical parameters, including initially affected sites, were compared among patients with various HLA-B27 subtypes. Results: In total, 431 AS patients (91.7%) were HLA-B27-positive. The most prevalent subtypes were HLA-B*2704 (89.8%) and HLA-B*2705 (8.8%) in patients with AS. Initially affected sites such as axial joint and peripheral joint were most common among HLA-B*2704positive patients (55.3% and 37.5%), HLA-B*2705-positive patients (55.3% and 31.5%) and HLA-B27 negative patients (66.7% and 30.8%). There were no significant differences in initially affected sites such as axial joint, peripheral joint, hip join, axial joint + peripheral joint, axial joint + hip, or peripheral joint + hip among above groups. Compared with HLAB*2704-positive patients, HLA-B*2705-patients demonstrated a significant increase in the incidence of uveitis (initial symptom, 5.3% vs. 0.5%, P = 0.042). Conclusion : Specific HLA-B27 subtypes were positively associated with particular initial symptoms. AS patients with HLA-B*2705 demonstrated a higher risk of uveitis than did AS patients with HLA-B*2704.

APLAR-0486

Anti-CCP antibodies and rheumatoid factor in ankylosing spondylitis Q JUN, WEI QIUJING, LIN ZHIMING, Z PINGPING, HU ZAIYING, LI QIUXIA, GU JIERUO

APLAR-0467

Smoking is related with disease activity and function limitation in AS Z LIN, Y JIANG, Z LIAO, QING LV, P ZHANG, Z HU, J GU 1

Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Objective: To investigate the relationship between cigarette smoking and pain, disease activity, functional limitation, and health assessment in Chinese patients with Ankylosing Spondylitis (AS). Method: Patients with AS (n = 683) from the mainland of China took part in a cross-sectional survey. Smoking status was obtained by a standardized questionnaire, involving smoking status (non-smokers, exsmokers, current smokers), the age when starting smoking, cigarette numbers a day and smoking status of family numbers. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), visual Analogue scale of pain, Health Assessment Questionnaire for Spondyloarthropathy (HAQ-S) were analyzed in terms of smoking status and relationship with pack-year history. Result: Of all the 683 patients, 168 are current smokers, while 108 were ex-smokers and 407 patients never smoked. Median scores of degree and duration of morning stiffness, overall pain, nocturnal back pain, overall back pain, CRP, BASDAI and BASFI score were all higher in the current smoker group compared to those who had never smoked (P < 0.05). In Spearman correlation analysis, pack years of smoking in current smokers were significantly associated with disease duration, morning stiffness (VAS) and duration, nocturnal back pain, overall back pain, CRP, and BASDAI (P < 0.01), and overall pain, BASFI and HAQ-S (P < 0.05). In multiple stepwise regression analysis, high disease activity was associated with current smoking, overall pain, morning stiffness, BASFI, nocturnal back pain and HAQ-S (P < 0.05) Conclusion: Cigarette smoking has a dose-dependent relationship with disease activity and correlates with more functional limitation and worse health assessment in AS. Physicians need to call on AS patients to quit smoking to improve their disease outcomes potentially.

Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: Anti-cyclic citrullinated peptide (anti- CCP) antibodies and rheumatoid factor (RF) has been found to not only in rheumatoid arthritis (RA), but also in systemic lupus erythematosus, psoriatic arthritis and other rheumatic diseases. This study aimed to investigate the prevalent of anti- CCP and RF in ankylosing spondylitis (AS). Methods: One hundred and seventy-six AS patients included in the study. Fourty-nine RA patients were control groups. All serum samples from patients and controls were applied with anti- CCP2 test kit. RF were tested using latex agglutination and ELISA. Results: There were 11 cases of anti-CCP -positive (6.25%), 8 patients with AS were RF *positive when applied with latex agglutination assay (4.55%). Twenty-six AS patients detected by ELISA were RF -positive (26/176, 14.7%), of which, 24 cases of RF-IgG -positive (24/176, 13.64%), 2 cases of IgA (2/176, 1.13%) and 3 cases of IgM (3/176, 1.71%) were positive. A total of 6 patients both anti- CCP and RF were positive. Out of 24 cases of RF-IgG positive AS patients, 23 cases were RF titer 3 times of the upper limit. The RF subtypes distribution in AS were different from that of RA (P < 0.05). Conclusion : AS patients have a similar frequency of anti-CCP than health controls, but have more incidence of RF in AS than previous reports, only with low titer positive.

APLAR-0469

Associations between initial symptoms and HLA-B27 subtypes in AS Q JUN, Z PINGPING, WEI QIUJING, LIN ZHIMING, HU ZAIYING, CAO SHUANGYAN, YANG MINGCAN, Z YANLI, GU JIERUO Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: Human leukocyte antigen (HLA)-B27 is closely associated with ankylosing spondylitis (AS). This study aimed to investigate the association between the initial symptoms and the HLA-B27 subtypes.


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Clinical Rheumatology – T09: Spondylarthropathies – biological and non-biological therapies

Clinical Rheumatology – T09: Spondylarthropathies – biological and nonbiological therapies

APLAR-0090

Alendronate for prevention of bone loss in ankylosing spondylitis A KHABBAZI, S GAFARZADEH Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Objectives: The aim of this study was the considering the efficacy of alendronate on the prevention of bone loss in patients with early ankylosing spondylitis. Methods and materials: In a randomized double blind placebo controlled study in Emam Reza hospital of Tabriz University of Medical Sciences, 24 patients with early ankylosing spondylitis was recruited to the study. The early ankylosing spondylitis criteria were: Schober index ≥5; normal hip joint in pelvic radiography; absence or rarity of syndesmophytes in spine radiography (Taylor index ≤1). They randomized with Randlist software to the treatment and control groups. Treatment and control groups received alendronate 70 mg/week and placebo respectively for 12 months. Before and 12 months after intervention bone densitometry by the DEXA method and Hologic QRD model instrument from lumbar and pelvic area was performed. Patients, assessing physicians and densitometry technician were blinded. Both groups received calcium 1000 mg/day and vitamin D 400 mg/day supplement. Results: The differences in the bone mineral density after 12 months in the treatment and control groups were non-significant. No case of clinically apparent vertebral and non-vertebral fracture was observed in the treatment and control groups. Conclusions : The results of our study suggest that alendronate is ineffective for prevention of bone loss in patients with early ankylosing spondylitis.

APLAR-0198

High CD154+ T cell of axial SpA is down-regulated by TNF-a inhibitor Z LIN, QU LIN, Z HU, P ZHANG, D LIN, OU JIN, Q WEI, D WU, J GU Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: To detect the differences of CD3 + CD154+ T-lymphocytes subtypes between healthy controls and active axial Spondyloarthritis (SpA) and observe the change of the percentage of CD3 + CD154+ T-lymphocytes after TNF-a inhibitor treatment in active axial SpA patients. Methods: Patients who fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial SpA had a BASDAI of ≥40 mm. Collecting data included gender, age, family history, arthritis, HLA-B27, hip involvement and CRP. Thirty-five patients received infliximab (5 mg/kg) at weeks 0, 2, 6, 12, and 39 patients received etanercept (50 mg once a week) for 12 weeks. At week 12, we used ASAS20 to evaluate the effect. The percentage of CD3 + CD154+ T-lymphocytes were detected in patients and healthy controls at baseline and week-12. Nonparametric test was used to analyze the percentage of subtypes of T-lymphocytes between healthy controls and patients. The same analysis was done between before and after TNF-a inhibitor treatment. Result: Fifty-eight healthy controls and 74 active axial SpA patients were included. Mean age was 26.28 9.08 years and 26.95 8.13 years for healthy controls and patients, respectively (P = 0.767). In patients, 89.19% (n = 66) patients were HLA-B27(+), 14.86% (n = 11) patients had positive family history, 34.43% (n = 24) had arthritis, 12.16% (n = 9) had hip involvement. Analogously, the percentage of CD3 + CD154+ T-lymphocytes on peripheral blood T-lymphocytes was significantly higher in axial SpA patients than in healthy controls (1.62 1.89% vs 0.79 0.52%, P = 0.000). At baseline, the percentage of CD3 + CD154+

T-lymphocytes was significantly higher in HLA-B27(+) patients than HLA-B27() ones (HLAB27+ vs HLA-B27-:1.77 1.95% vs 0.41 0.27%, P = 0.005). Compared with baseline, the percentage of CD3 + CD154+ T-lymphocytes significantly decreased to 0.87 0.49% after 12-week treatment (P = 0.000) (Fig. 1). Conclusion: The CD3 + CD154+ T-lymphocytes is over-expressed on T-lymphocytes in peripheral blood of active SpA patients and can be down-regulated by TNF- a inhibitor therapy. High-percentage of CD3 + CD154+ T-lymphocytes was associated with HLA-B27 positive in axial SpA patients.

APLAR-0299

Repeated interferon gamma release assays in Ankylosing Spondylitis CN SON1, TH KIM1, JB JUN1, IH SUNG2, DH YOO1 1

Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Orthopaedic Surgery, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea 2

Background: Anti-tumor necrosis factor alpha (Anti-TNFa) is often used in patients with rheumatic diseases who do not respond to conventional treatment. Risk of tuberculosis infection is high in patients receiving anti-TNFa. However, the follow-up latent tuberculosis infection (LTBI) testing in Ankylosing spondylitis (AS) patients receiving anti-TNFa has rarely been studied. Because of increasing use of anti-TNFa in AS patients, a well-established guideline needs to be set up. Methods: The study participants (n = 127) were enrolled from September 2008 to August 2012, among AS patients registered in tertiary care center. These patients had a negative interferon gamma release assay (IGRA) screening before receiving anti-TNFa and were evaluated by follow-up IGRA for detection of LTBI until November 2013. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFa, including type and treatment duration. To compare the characteristics of AS and RA patients, we also reviewed 26 RA patients in the same study design. Results : The median interval between initial and follow-up IGRAs in patients was 21.5 months, and the median age was 35.3 years. Among the 127 AS patients, IGRA conversion was found in 10 patients (7.9%). IGRA conversion rate was higher in older patients (≥40 years) (9/39, 23.1%) than it was in younger patients ( 0.05). At week 24, FD in the lumbar spine (1.3 2.2 vs. 1.8 2.6, P < 0.05) and in SI joints (0.9 1.1 vs. 1.2 1.6, P < 0.05) seen by MRI increased significantly after receiving adalimumab, while FD remained stable (for lumbar spine, 1.0 2.1 vs. 1.4 3.2; for SI joints, 0.9 1.3 vs. 1.1 1.7, both P > 0.05) in patients receiving mobic. Conclusion: Our study confirmed that both adalimumab and mobic were effective in reducing inflammation in AS. And we found that adalimumab increase more FD than mobic in active AS patients.

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Clinical Rheumatology – T09: Spondylarthropathies – biological and non-biological therapies

APLAR-0314

Adalimumab reduces enthesitis in AS patients: an ultrasound study

Conclusion: TNF-a inhibitor can significantly ameliorates the inflammation of hip joints in SpA.

ZM LIN, ZY HU, DF LIN, ML XU, PP ZHANG, ZT LIAO, JR GU Department of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

APLAR-0442

Relapse of 5 years follow-up for AS patients with etanercept treatment Z LIN, Z HU, P ZHANG, OU JIN, D LIN, Z LIAO, Q WEI, S CAO, J GU

Objective: To evaluate the feasibility of using power Doppler ultrasound (PDUS) to detect enthesitis after adalimumab (a TNF-alpha antagonist) treatment in active ankylosing spondylitis (AS) patients. Methods: This was a randomized, double-blind, placebo-controlled study. Active AS patients received 40 mg adalimumab (n = 22) or placebo (n = 19) every other week during an initial 12-week double-blind period, and all switched to adalimumab treatment for another 12 weeks. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), C-reactive protein (CRP), Ankylosing Spondylitis Disease Activity Scores (ASDAS) were measured and inflammation in enthesis were detected by PDUS at baseline, week 12 and week 24. The following entheseal sites were examined bilaterally in both planes: insertion of quadriceps femoris into patella, the superior patellar tendon insertion, the inferior patellar tendon insertion at the anterior tibial tuberosity, Achilles tendon, and plantar fascia insertion into the calcaneus. We used sonographic enthesitis index (SEI) to score the enthesitis. Results : The total PDUS scores of enthesitis in active AS patients decreased significantly after 24 weeks treatment of adalimumab (19.4 11.9 vs. 15.2 10.5, P = 0.001). And obvious improvements in clinical assessments (BASDAI, BASFI, CRP and ASDAS reduced, all P < 0.05) were also observed after 24 weeks of adalimumab. But the PDUS scores of enthesitis in AS patients did not change statistically after 12 weeks treatment of adalimumab (19.4 11.9 vs. 17.0 11.3, P = 0.055) or placebo (14.4 7.3 vs. 15.4 6.9, P = 0.436). And the PDUS score of enthesitis did not correlate with any clinical assessments (all P > 0.05). Conclusion : Our study found that adalimumab was highly effective in reducing inflammation in enthesis in active AS patients as detected by power Doppler ultrasound.

Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: To detect relapse status after etanercept treatment and distinguish if the duration of etanercept treatment affect relapse of AS patients who reached satisfied response for etanercept treatment. Method: 39 active AS patients had finished a study-after a 6 weeks, random double-blind, placebo-controlled trial of etanercept treatment, keep treating with etanercept for 6 weeks. After 12 weeks trial, 35 AS patients reached ASAS20 response. All 35 patients were included in placebo group (n = 18) and etanercept group (n = 17) in previous study. Besides stopping etanercept treatment, all other medicine were maintained. We followed up patients for BASDAI scores per 2 weeks by telephone to evaluate relapse of these 35 patients. The definition of relapse was that BASDAI score goes back to 80 percentages of it in baseline, BASDAI rises 2 points than it in last treatment. The distribution of relapse rate curve analysis was using between above two group with Kaplan-Meier method. Likewisely, the suspected susceptible relapse factors, which included gender, age, onset age, duration, baseline data (BAS-G, BASDAI, BASFI, hip involved, arthritis and CRP), were analzed by Cox regression model. Result: After 5 years following-up, all 35 patients relapsed. The remission duration before relapse weren’t significant difference between these two group (placebo:90.79 90.18 weeks, enbrel:100.76 91.05 weeks, P = 0.934). Relapse rates were no significant difference between these two group with Kaplan-Meier analysis (P = 0.629). Conclusion : The duration of etanercept treatment cannot affect relapse of AS patients who reached satisfied response for etanercept treatment.

APLAR-0433

TNF-a inhibitor ameliorates the inflammation of hip joints in SpA Z LIN, M ZHAO, P ZHANG, L FANG, Z HU, Z LIAO, J GU

APLAR-0458

Biosimilar infliximab in the management of Reiters syndrome A MAGBITANG, ML TEE, AL LINDAIN

Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Objective: To evaluate the efficacy of TNF-a inhibitor treatment in hip joint of SpA patients. Method: Including criteria is: 1) patients with hip involvement who met ASAS axial or peripheral criterion, 2) BASDAI ≥30 mm. TNF-a inhibitor was used in all patients for 24 weeks. MRI examination of hip joints was performed at week 0 and 24. The primary endpoint is ASAS20, ASAS partial remission and hip joint MRI score. A MRI score system was performed to evaluate the hip inflammation and effusion. The most abnormal hip’s coronal levels on the T2 STIR sequence was chosen and divided into 4 quadrants. The inflammatory lesion of hip joint was graded with a range of 0~3: no active inflammatory lesions (grade 0), little (25% of the bone surface, grade 1), moderate (25*50% of the bone surface, grade 2), severe (more than 50% of the bone surface, grade 3) active inflammatory lesions. The hip joint effusion was graded with a range of 0~3: no effusion (grade 0), little (25% of the volume of articular cavity, grade 1), moderate (25*50% of the volume of articular cavity, grade 2), severe (more than 50% of the volume of articular cavity, grade 3). Result: 18 patients (using infliximab) and 7 patients (using etanercept) were included. After 24 weeks treatment, 1) 23 of 25 AS patients (92.0%) achieve ASAS20 response . 2) 15 of 25 patients (60.0%) reached ASAS partial remission. 3) The active inflammatory’s MRI score of hip joints lesions were improved significantly after 24 weeks treatment (from 8.89 3.93 to 4.32 3.25). And the hip effusion’s MRI score showed an significant decrease (from 3.42 1.77 to 1.32 0.77).


Medicine Section of Rheumatology, University of the Philippines Philippine General Hospital, Manila, Philippines Infliximab has been reported to be effective in the treatment of Reiter’s Syndrome, a reactive form of seronegative spondyloarthropathy. This paper reports the first time a biosimilar infliximab was used in the management of this disease. A 45-year-old man with Reiter’s syndrome was treated with biosimilar infliximab (Remsima) 200 mg intravenously at Weeks 0, 2, and 8 and 16. He presented with urethritis, conjunctivitis and arthritis involving his ankles, elbows, wrists and knees. Laboratory assessment revealed urinalysis: WBC 15–20/hpf, RBC 0–1/hpf; ESR 40 mm/h; and CRP 125 mg/dL. Rheumatoid factor and HIV screen were negative. We drained 55 cc of fluid from his left knee. Synovial fluid analysis showed RBC 430/cumm; WBC 5040/ cumm with 55% PMN. Fluid GS/CS and crystal analysis also turned out negative. His condition did not improve despite 2 weeks of appropriate doses of NSAIDS, methotrexate, systemic and intra-articular corticosteroid. We then administered 200 mg of biosimilar infliximab which resulted to improvement of symptoms within 1 week after the infusion. We then administered three more infusions of biosimilar infliximab at weeks 2, 8 and 16. Following four doses of biosimilar infliximab administered with weekly dose of 12.5 mg of methotrexate, the patient is now symptom free. His acute phase reactants are also normal.

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Clinical Rheumatology – T10: Psoriatic arthritis

Clinical Rheumatology – T10: Psoriatic arthritis

APLAR-0289

APLAR-0291

Tender and swollen joint count improvement with apremilast

Long-term safety/tolerability of Apremilast: pooled analysis

S HALL1, M CUTOLO2, PJ MEASE3, D GLADMAN4, A KAVANAUGH5, AO ADEBAJO6, JJ GOMEZ-REINO7, J WOLLENHAUPT8, G SCHETT9, E LESPESSAILLES10, CC HU11, RM STEVENS11, CJ EDWARDS12, CA BIRBARA13

P NASH1, AO ADEBAJO2, PJ MEASE3, A KAVANAUGH4, D GLADMAN5, JJ GOMEZ-REINO6, J WOLLENHAUPT7, M CUTOLO8, G SCHETT9, E LESPESSAILLES10, K SHAH11, CC HU11, RM STEVENS11, CJ EDWARDS12, CA BIRBARA13

1

1

Department of Rheumatology, Cabrini Medical Centre, Malvern VIC, Australia, Department of Rheumatology, University of Genova, Genova, Italy, 3Department of Rheumatology, Swedish Medical Center and University of Washington School of Medicine, Seattle, USA, 4Department of Rheumatology, Toronto Western Hospital, Toronto Ontario, Canada, 5Department of Rheumatology, University of California at San Diego, San Diego, USA, 6Department of Rheumatology, University of Sheffield, Sheffield, UK, 7Department of Rheumatology, Hospital Clinico Universitario, Santiago, Spain, 8Department of Rheumatology, Schon Klinik Hamburg Eilbek, Hamburg, Germany, 9Department of Rheumatology, University Erlangen-Nuremberg, Erlangen, Germany, 10Department of Rheumatology, University of Orleans, Orleans, France, 11Department of Rheumatology, Celgene Corporation, Warren, USA, 12 Department of Rheumatology, University Hospital Southampton, Southampton, UK, 13 Department of Rheumatology, University of Massachusetts Medical School, Worchester, USA

Department of Rheumatology, University of Queensland, Brisbane, Australia, Department of Rheumatology, University of Sheffield, Sheffield, UK, 3Department of Rheumatology, Swedish Medical Center and University of Washington School of Medicine, Seattle, USA, 4Department of Rheumatology, University of California at San Diego, San Diego, USA, 5Department of Rheumatology, Toronto Western Hospital University of Toronto, Toronto Ontario, Canada, 6Department of Rheumatology, Hospital Clinico Universitario, Santiago, Spain, 7Department of Rheumatology, Schon Klinik Hamburg Eilbek, Hamburg, Germany, 8Department of Rheumatology, University of Genova, Genova, Italy, 9Department of Rheumatology, University Erlangen-Nuremberg, Erlangen, Germany, 10Department of Rheumatology, University of Orleans, Orleans, France, 11Department of Rheumatology, Celgene Corporation, Warren, USA, 12Department of Rheumatology, University Hospital Southampton, Southampton, UK, 13Department of Rheumatology, University of Massachusetts Medical School, Worcester, USA

PALACE 1, 2, and 3 compared the efficacy/safety of apremilast (APR) with placebo in patients with active PsA despite prior conventional DMARDs and/or biologics. Swollen and tender joint counts (SJC/TJC) were examined across these 3 studies. Patients were randomized 1:1:1 to placebo, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no) in PALACE 1, 2, and 3 and baseline psoriasis involvement of BSA (

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