Current Medical Research & Opinion

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

0300-7995 doi:10.1185/03007995.2014.969368

Vol. 30, No. 12, 2014, 2515–2521

Article FT-0303.R1/969368 All rights reserved: reproduction in whole or part not permitted

Original article Comparing the risk of developing uveitis in patients initiating anti-tumor necrosis factor therapy for ankylosing spondylitis: an analysis of a large US claims database

Daniel Wendling University of Franche-Comte´ and CHU de Besanc¸on, Department of Rheumatology, Besanc¸on, France

Avani Joshi Patrick Reilly AbbVie Inc., North Chicago, IL, USA

Yash J. Jalundhwala University of Illinois at Chicago, Chicago, IL, USA

Manish Mittal Yanjun Bao AbbVie Inc., North Chicago, IL, USA Address for correspondence: Daniel Wendling MD PhD, Head of Service, University of Franche-Comte´ and CHU de Besanc¸on, Department of Rheumatology, Boulevard Fleming, Besanc¸on, France 25030. Tel.: +33 03 81 66 82 41; Fax: +33 03 81 66 86 86; [email protected] Keywords: Ankylosing spondylitis – Anti tumor necrosis factor – Extra-articular manifestation – Retrospective study – Uveitis Accepted: 19 September 2014; published online: 8 October 2014 Citation: Curr Med Res Opin 2014; 30:2515–21

Abstract Objective: To compare the risk of developing uveitis in patients initiating anti-tumor necrosis factor (anti-TNF) agents (adalimumab, etanercept, and infliximab) for ankylosing spondylitis (AS). Methods: Anti-TNF-naive patients with a diagnosis of AS and without a history of uveitis (N ¼ 2115) who subsequently initiated anti-TNF therapy for AS were identified in a large claims database (2005 to 2011). A multivariate Cox proportional-hazards model was used to compare the risk of uveitis in patients who received etanercept or infliximab vs adalimumab. Results: The median number of days to the first occurrence of uveitis after initiation of anti-TNF was 191. Among the three anti-TNF groups, the median time to event of uveitis was longest in patients taking adalimumab (243 days), followed by etanercept (182 days) and infliximab (144 days). The incidence rate for uveitis over 1 year was lowest for patients who received adalimumab (2.4%, N ¼ 717), highest for patients who received etanercept (4.5%, N ¼ 1087), and intermediate for patients who received infliximab (3.2%, N ¼ 311). The risk of uveitis was 1.9 times higher in patients receiving etanercept compared with those taking adalimumab (hazard ratio [HR]: 1.91, 95% confidence interval [CI]: 1.1 to 3.31). For patients taking infliximab, the risk of uveitis was not statistically significantly different (HR: 1.35, 95% CI: 0.62 to 2.95) compared to adalimumab. Conclusion: The results indicated that initial adalimumab therapy is associated with a significantly lower risk of developing uveitis compared to initial etanercept therapy in patients diagnosed with AS and no prior history of uveitis; however, the risk was not different between adalimumab and infliximab. Limitations to consider when interpreting this conclusion include that disease-level clinical data, such as disease duration, were not available for inclusion in the model and that risk of uveitis beyond 1 year was not evaluated.

Introduction Ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease that primarily affects the sacroiliac joints and causes inflammatory back pain, is often accompanied by inflammatory extra-articular manifestations such as Crohn’s disease, psoriasis, and uveitis1,2. In a systematic literature review of extra-articular manifestations in patients with AS, acute anterior uveitis (26%) was more common than psoriasis (9%) or inflammatory bowel disease ! 2014 Informa UK Ltd www.cmrojournal.com

Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

2515

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

Current Medical Research & Opinion Volume 30, Number 12

December 2014

(7%)3. Other studies have estimated that 25% to 50% of patients experience at least one episode of uveitis during the course of AS4–8. Characteristics of uveitis in patients with AS include predominantly acute, unilateral onset; anterior location; strong association with human leukocyte antigen (HLA)-B27 positivity; and tendency to recur, often in the opposite eye6,9–11. In addition, the incidence of uveitis increases with longer disease duration, ranging from 17% for patients with disease duration 510 years to 39% for patients with disease duration 420 years3,12. Uveitis is a painful, often recurrent, and potentially serious inflammation of the eye. It is the most preventable cause of blindness worldwide and also has a negative effect on health-related quality of life13. AS patients with extraarticular manifestations utilize more medical resources and incur more health care costs compared with AS patients who do not develop extra-articular manifestations14. Complications of inadequately treated uveitis include cataract formation, glaucoma, and maculopathy, all of which can lead to visual acuity loss and ultimately blindness15. In patients with spondyloarthropathies, uveitis was associated with reduced visual acuity in 8% of patients; and approximately 50% of patients had at least one recurrent flare6. Tumor necrosis factor (TNF) is involved in the pathogenesis of both uveitis and AS. TNF is elevated in the aqueous humor and serum of patients affected by uveitis and the joints of patients with AS16,17. Anti-TNF therapy has been shown to reduce ocular inflammation and preserve vision in patients with sight-threatening uveitis18, and there is considerable interest in the use of biologic treatments for uveitis and other ocular inflammatory disorders19. The anti-TNF agents adalimumab and infliximab have been shown to reduce uveitis flares in patients with AS20–23, whereas evidence for the ability of etanercept to prevent uveitis flares is mixed1,20,22,24,25. Conversely, uveitis develops in some patients whose articular symptoms are well controlled with anti-TNF therapy, suggesting that the ocular and articular inflammation develop via different pathways6,12,25. The degree to which new-onset uveitis occurs in patients receiving anti-TNF therapy has been characterized in a retrospective cohort study, with the majority of cases occurring during therapy with etanercept; of 31 cases of uveitis identified, 19 were in AS, 4 were in psoriatic arthritis, 6 were in rheumatoid arthritis, and 2 were in juvenile idiopathic arthritis25. Of the 19 cases associated with AS, that anti-TNF agent at the time of the first onset of uveitis was etanercept in 12 cases, infliximab in 4 cases, and adalimumab in 3 cases; the pattern of results was similar among 121 cases identified in a systematic literature review25. The risk of developing uveitis in anti-TNF-naive patients with no prior history of uveitis has not been quantified to date. The objective of this retrospective, observational study was to compare the risk of 2516

Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

developing uveitis between patients initiating adalimumab and patients initiating etanercept or infliximab for AS.

Patients and methods Data source Patients were identified using the Truven Health MarketScan Commercial ClaimsÕ and Encounters research database from the years 2005 to 2011. The database covers all census regions in the United States, but predominantly the South and North Central/Midwest regions. It contains health service claims data of approximately 100 third-party payers, including employers and health plans for approximately 170 million covered lives since 1995. MarketScan is compliant with the Health Insurance Portability and Accountability Act. The patient-level data include medical claims for inpatient, outpatient, and emergency department care; prescription drug claims; and individual eligibility and demographics. The database has a strong longitudinal component; and data are validated to ensure complete, accurate, and reliable claims and enrolment data.

Study design Figure 1 depicts the study design and patient follow-up period. Patients with AS (International Statistical Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 720.0) were identified using the MarketScan research database from years 2005 to 2011. First diagnosis was defined as the AS index date. First use of adalimumab, etanercept, or infliximab on or after AS index date was defined as the anti-TNF index date. All patients had to have at least 6 months of continuous eligibility in their health plan before the anti-TNF index date and 12 months after the anti-TNF index date. Uveitis was identified using ICD-9-CM codes (Figure 1).

Inclusion/exclusion criteria Anti-TNF-naive AS patients who had no previous history of uveitis were selected for analysis (Figure 2). Based on the anti-TNF therapy initiated on the index date, patients were classified into three groups: infliximab users, etanercept users, and adalimumab users. Patients having an event of uveitis before the anti-TNF index date were excluded. Patients who received any of the three anti-TNF agents and/or had a diagnosis of rheumatoid arthritis (ICD-9 code 714.0), psoriasis (ICD-9 code 696.1), psoriatic arthritis (ICD-9 code 696.0), Crohn’s disease (ICD-9 code 555.x) or ulcerative colitis (ICD-9 code 556.x) within the 6 months prior to anti-TNF index date were excluded. www.cmrojournal.com ! 2014 Informa UK Ltd

Current Medical Research & Opinion Volume 30, Number 12

12-Month Treatment Period for Identification of NewOnset Uveitisb

6-Month Baseline Period

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

December 2014

AS Index Date

Anti-TNF Index Date

-First AS diagnosisa

-First dose -No previous anti-TNF use of anti-TNF prior to anti-TNF index date therapyd -No uveitis prior to anti-TNF index dateb -No history of other comorbid inflammatory diseases prior to anti-TNF index datec

-AS patients with no uveitis diagnosis prior to initiation of anti-TNF therapy for AS

Figure 1. Study design. aAS diagnosis according to ICD-9-CM code 720.0 from the Truven Health MarketScan Commercial Claimsâ and Encounters database (2005–2011). bICD-9-CM codes for uveitis: 364.00–364.02, 364.10, 364.11, 364.2, 364.3, 364.21, 364.22, 360.13, 360.19, 360.11, 360.1, 360.12, 363.00363.06, 363.1x, 363.2x, 130.2, 362.18, 115.02, 115.12, 364.24, 091.51, 090.0, 090.5, 095.8, 094.83, 091.51, 017.3x, and 362.12. cICD-9-CM codes for concomitant inflammatory conditions prior to index date: rheumatoid arthritis, 714.0; psoriatic arthritis, 696.0; psoriasis, 696.1; ulcerative colitis, 556.x, and Crohn’s disease, 555.x. dAdalimumab, etanercept, or infliximab. AS, ankylosing spondylitis; ICD-9-CM, International Statistical Classification of Diseases, 9th Revision, Clinical Modification; TNF, tumor necrosis factor.

Outcome measures and statistical analysis Patients with AS diagnosis between 2005 and 2011 (N=52,367)

Patients receiving adalimumab, etanercept, or infliximab on or after AS index date (N=13,815)

≥6 months (182 days) of eligibility before and ≥1 year (365 days) of eligibility after initiation of anti-TNF therapy (N=5,187)

Patients receiving adalimumab, etanercept, or infliximab in the 6 months prior to anti-TNF index date are excluded (N=3,313)

Patients with prior comorbid inflammatory disease diagnosis (rheumatoid arthritis, psoriatic arthritis, psoriasis, Crohn’s disease, ulcerative colitis) are excluded (N=2,406)

Patients with diagnosis of uveitis prior to initiation of anti-TNF therapy are excluded (N=2,115)

Adalimumab (N=717)

Etanercept (N=1,087)

Infliximab (N=311)

Figure 2. Flowchart of sample selection. AS, ankylosing spondylitis; TNF, tumor necrosis factor.

! 2014 Informa UK Ltd www.cmrojournal.com

A Cox proportional-hazards model was used to analyze time to first occurrence of uveitis in the post-treatment period in the sample of anti-TNF-naive patients with no history of uveitis, with censoring 365 days after the anti-TNF index date. Hazard ratios (HRs) were calculated from a multivariate model controlling for age, sex, and medication use in the 6 months prior to the anti-TNF index date. Data management and analysis were accomplished via PC-SAS (SAS 9.2 for Windows, SAS Institute Inc., Cary, NC, USA), with an a priori alpha set at 0.05 to determine statistical significance.

Results Sample characteristics A total of 2115 anti-TNF-naive patients with AS were identified using the inclusion/exclusion criteria. Of these, 717 patients received adalimumab, 1087 received etanercept, and 311 received infliximab. Patient demographics and medication use are summarized in Table 1. The mean age of patients ranged from 40.5 years for those who received etanercept to 43.6 years for those who received infliximab (p ¼ 0.0004). Nonsteroidal antiinflammatory drug (NSAID) use differed between groups (p ¼ 0.0444); 63% of patients in the adalimumab and etanercept groups received NSAIDs compared with 55% in the infliximab group. Use of disease-modifying Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

2517

Current Medical Research & Opinion Volume 30, Number 12

December 2014

Table 1. Baseline demographics and medication use during the 6 month pretreatment index period. Adalimumab (N ¼ 717)

Etanercept (N ¼ 1087)

Infliximab (N ¼ 311)

p Value

41.6 (12.0) 59.7 62.9 19.7 44.4 41.7

40.5 (12.5) 62.4 62.6 20.0 39.4 36.3

43.6 (12.7) 56.6 55.3 18.0 44.1 40.8

0.0004 0.1517 0.0444 0.7431 0.0745 0.0535

Mean age (SD), yrs Men (%) NSAID use (%) DMARD use (%) Opiate use (%) Other pain medication use (%)

DMARD, disease-modifying antirheumatic drug; NSAID, nonsteroidal antiinflammatory drug; SD, standard deviation; yrs, years.

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

Table 2. Uveitis during the 12 month post-treatment index period. Adalimumab (N ¼ 717)

Etanercept (N ¼ 1087)

Infliximab (N ¼ 311)

Total (N ¼ 2115)

17 (2.4) 243

49 (4.5) 182

10 (3.2) 144

76 (3.6) 191

Patients with 1 uveitis event, n (%) Median days to first uveitis event

antirheumatic drugs (DMARDs), opiates, and other pain medications was similar between groups.

Time to event and risk of uveitis Overall, 3.6% (76 of 2115) of patients with AS had at least one event of uveitis. For the entire sample, the median number of days after initiation of anti-TNF therapy to the uveitis event was 191. Among the three anti-TNF groups, the median time to event for uveitis was longest in patients taking adalimumab (243 days), followed by etanercept (182 days) and infliximab (144 days) (Table 2). Although analysis of the median time to onset of first uveitis attack was not statistically significantly different between groups, results suggest that patients initiating adalimumab took longer to develop uveitis compared with those initiating etanercept and infliximab. The percentage of patients with an event of uveitis during the 1 year follow-up period was lowest in the group of patients who initiated adalimumab (2.4%), followed by infliximab (3.2%) and etanercept (4.5%). The estimates from the adjusted Cox proportional hazards regression are presented in Figure 3. In the post-treatment period, the risk of uveitis was 1.9 times higher in patients receiving etanercept compared with those receiving adalimumab (hazard ratio [HR]: 1.91, 95% CI: 1.1 to 3.31). Comparisons of infliximab vs adalimumab (HR: 1.35, 95% CI: 0.62 to 2.95) and etanercept vs infliximab (HR: 1.42, 95% CI: 0.71 to 2.80) for the risk of uveitis were not statistically significant.

Discussion Preliminary evidence suggests that anti-TNF therapy is effective for preventing uveitis and reducing flares in 2518

Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

patients with rheumatic diseases20–22,24–26. In a review of clinical trial data, Braun et al. (2005)20 found that infliximab or etanercept therapy reduced the incidence of anterior uveitis in patients with AS compared with placebo (6.8/100 patient-years vs 15.6/100 patient-years; p ¼ 0.01), although numerically more cases were associated with etanercept (7.9/100 patient-years) than with infliximab (3.4/100 patient-years). A more recent study of clinical trial data found lower rates of uveitis for etanercept vs placebo (8.6/100 patient-years, 95% CI: 4.5, 14.2 vs 19.3/100 patient-years, 95% CI: 11.0, 29.8, respectively; p ¼ 0.03), whereas rates of uveitis for etanercept and sulfasalazine in active-controlled trials were similar (10.7/100 patient-years, 95% CI: 5.5, 17.6; and 14.7/100 patientyears, 95% CI: 6.4, 26.5, respectively; p ¼ 0.49)26. A large, prospective, open-label, multicenter study of adalimumab in patients with AS estimated that the rate of uveitis prior to receiving anti-TNF therapy was 15 to 16 per 100 patient-years of observation21. In that study, treatment with adalimumab reduced the rate of anterior uveitis flares by 51% in all patients with active AS, 58% in patients with a history of uveitis, 68% in patients with a recent history of uveitis, 50% in patients with symptomatic uveitis at baseline, and 45% in patients with chronic uveitis21. The results of the present retrospective study, in which adalimumab was associated with a significantly lower risk of new-onset uveitis compared with etanercept and a rate similar to that of infliximab, are consistent with several other studies22,24,25. A survey of French rheumatologists found that new-onset uveitis occurred more frequently with etanercept therapy, which accounted for 83% (126 of 152 cases) of the retrospective cohort and literature cases combined25. A different survey of 46 patients conducted in a single French hospital center reported that, among spondyloarthropathy patients with at least one www.cmrojournal.com ! 2014 Informa UK Ltd

Current Medical Research & Opinion Volume 30, Number 12

Etanercept

Adalimumab

December 2014

Infliximab

6% Hazard Ratio 1.905 1.346 1.415

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

Uveitis Incidence Rate

Comparison Etanercept vs adalimumab Infliximab vs adalimumab Etanercept vs infliximab

95% Cl 1.096, 3.310 0.615, 2.947 0.714, 2.804

P value 0.0223 0.4566 0.3204

4%

2%

0% 0

1

2

3

4

5

6

7

8

9

10

11

12

Months to Event

Figure 3. Adjusted hazard rates: time to uveitis following initiation of anti-TNF therapy for AS (mean of covariates method, censored at 365 days). Multivariate Cox proportional-hazard model adjusted for age, sex, and medication use in the 6 month period prior to initiation of the index anti-TNF therapy. AS, ankylosing spondylitis; CI, confidence interval; TNF, tumor necrosis factor.

uveitis flare, adalimumab and infliximab significantly decreased uveitis flares, whereas etanercept did not22. Likewise, uveitis cases identified in two adverse event databases found significantly more cases associated with etanercept therapy compared with infliximab or adalimumab therapy24; however, there were no differences between adalimumab and infliximab therapy. Unique characteristics of the present study that add to the current body of knowledge include that rates of newly diagnosed uveitis associated with three established anti-TNF therapies were assessed simultaneously in a large population of anti-TNF-naive patients with no prior history of uveitis. Although the mechanism underlying the variable pattern of uveitis with etanercept and adalimumab or infliximab is unclear, it is unlikely that differences between the groups could be explained by differences in DMARD use, for DMARD use was similar across the three groups (p ¼ 0.7431, Table 1). Similarly, the use of NSAIDs may be a potential confounder, for NSAIDs have been reported to reduce the rate of uveitis27; however, NSAID use was equivalent in the adalimumab and etanercept groups, and the Cox proportional-hazard model adjusted for it as a potential confounding factor. The potential impact of concomitant sulfasalazine, which has been shown to reduce uveitis flares, was not assessed in our analysis26,28–30. Finally, the available data did not allow the present analysis to examine the association of uveitis with hypertension and atherosclerosis in patients with AS, as reported in a recently published study31. ! 2014 Informa UK Ltd www.cmrojournal.com

As with all retrospective claims database studies, the current analysis had some inherent limitations, including that no disease-level data were available for the sample. For example, the database did not provide information regarding the incidence of peripheral arthritis, enthesitis, or HLA-B27 positivity; disease activity level or severity; clinical response to anti-TNF therapy; or treatmentrelated adverse events. Likewise, duration of AS, which has been shown to be related to the risk of uveitis in AS3, was not available for inclusion in the model. In addition, the present study did not examine the risk of uveitis beyond the 1 year post-treatment index period because many uveitis cases (40%) were lost to follow-up. Other anti-TNF therapies such as golimumab and certolizumab were new drugs approved during the study period and therefore were not compared. Although 11.5% of study patients were identified as switching from one anti-TNF to another during the 1 year study period, persistence with the index anti-TNF was assumed; however, any changes in dosage, switching to a different anti-TNF therapy, or discontinuing the index anti-TNF therapy during the 1 year study period would be unlikely to affect the results substantially. According to a recent study also using the MarketScan database from 2005 to 2009, the majority of AS patients in the first year after initiating anti-TNF therapy were persistent or restarted the index agent after a treatment gap; and the percentages of patients who were persistent, restarted, switched, or discontinued therapy with adalimumab, etanercept, or infliximab were similar32. Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

2519

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

Current Medical Research & Opinion Volume 30, Number 12

December 2014

A few studies have provided preliminary evidence that adalimumab and infliximab are effective for treating refractory uveitis21,23,33,34. Moreover, an expert panel recently endorsed adalimumab and infliximab as potential second-line agents for the treatment of severe ocular inflammatory conditions, including severe uveitis associated with seronegative spondyloarthropathy, in patients who failed or are not candidates for antimetabolite or calcineurin inhibitor immunomodulation; the panel also considered these agents to be preferable to etanercept19. Although the present study cannot address whether antiTNF therapy is effective for treating symptomatic uveitis in patients with AS or in preventing uveitis flares in patients with a history of chronic uveitis, because the study population was selected for patients without a prior uveitis diagnosis, comparison of the rates of first-onset uveitis after initiation of treatment gives an indication of the potential effect of anti-TNF therapy on development of uveitis in patients with AS. Comparison with patients who did not receive anti-TNF therapy after diagnosis of AS could also be of interest, although such patients might have different disease characteristics (e.g., less severe AS or shorter disease duration) that could confound the comparison. Assessment of visual outcomes such as acuity loss or blindness in patients with comorbid AS and uveitis is limited; thus, further study on this topic is warranted. In addition, research is needed to identify AS patients potentially at greater risk of developing uveitis, which can be considered a paradoxical effect when it develops or is exacerbated in a patient receiving anti-TNF therapy because these agents would be expected to improve or prevent this condition. Potential explanations for differential effects of the monoclonal anti-TNF agents (adalimumab and infliximab) and the soluble receptor agent (etanercept) on uveitis are still a matter of debate in rheumatology practice; this debate applies also to differential effects in Crohn’s disease35,36. Monoclonal antibodies and soluble receptor agents exhibit different immunological behavior in that etanercept also inhibits TNF-beta and the binding of soluble receptors with TNF-alpha prevents its clearance and increases its half-life36. Other differences between the monoclonal antibodies and etanercept include that etanercept does not induce apoptosis and it increases lymphocyte-stimulating cytokines36. The consistent finding of uveitis occurring more frequently with etanercept than with other anti-TNF agents suggests that development of uveitis with the monoclonal antibodies may be related to underlying features of the disease, whereas development of uveitis with etanercept may follow the paradoxical paradigm and be induced by the biologic activity and/or cytokine imbalance associated specifically with soluble receptor agents. Our study may not be conclusive regarding a class effect of monoclonal antibodies, for the risk of developing uveitis in patients who received etanercept 2520

Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

was numerically higher but not statistically significant compared with those receiving infliximab, possibly because of the small sample for infliximab. Overall, these results suggest that monoclonal antibodies, rather than soluble receptor agents, may be the preferred anti-TNF therapy for AS patients with uveitis; however, further study is warranted.

Conclusion In conclusion, this retrospective, observational claims database study reinforces other studies that reported differences in the pattern of uveitis cases after initiation of adalimumab, etanercept, or infliximab for AS and augments the available data regarding the relationship between anti-TNF therapy and uveitis. The risk of developing uveitis was lower in anti-TNF-naive patients treated with adalimumab following diagnosis of AS compared with patients treated with etanercept; however, the risk was not significantly different between adalimumab and infliximab or between etanercept and infliximab.

Transparency Declaration of funding This study was funded in full by AbbVie Inc., North Chicago, IL, United States. AbbVie Inc. participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. All authors had access to the data and participated in the development, review, approval, and decision to submit this publication. Declaration of financial/other relationships D.W. has disclosed that he has participated in advisory boards for AbbVie, MSD, Pfizer, Roche Chugai, and Sobi; received speaking fees from AbbVie, MSD, Pfizer, Roche Chugai, Amgen, UCB, Nordic, and BMS; and received grants from AbbVie, Pfizer, and Roche Chugai. A.J. has disclosed that he is a shareholder in AbbVie and an employee of AbbVie. P.R. has disclosed that he is a contractor with AbbVie. Y.J.J. has disclosed that he is from the University of Illinois at Chicago and is a summer intern at AbbVie. M.M. has disclosed that he is a shareholder in AbbVie and an employee of AbbVie. Y.B. has disclosed that she is a shareholder in AbbVie and an employee of AbbVie. CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose. Acknowledgments Medical writing services were provided by Cathryn M. Carter MS and Tracey Fine MS ELS of Arbor Communications Inc., Ann Arbor, Michigan, United States; this support was funded by AbbVie.

www.cmrojournal.com ! 2014 Informa UK Ltd

Current Medical Research & Opinion Volume 30, Number 12

Previous presentation: Data from the manuscript have been previously presented at the European League Against Rheumatism Congress, 25–28 May 2011, London, United Kingdom.

Curr Med Res Opin Downloaded from informahealthcare.com by University of Guelph on 01/31/15 For personal use only.

References 1. Elewaut D, Matucci-Cerinic M. Treatment of ankylosing spondylitis and extraarticular manifestations in everyday rheumatology practice. Rheumatology (Oxford) 2009;48:1029-35 2. Bremander A, Petersson IF, Bergman S, Englund M. Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis. Arthritis Care Res 2011;63:550-6 3. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. Prevalence of extraarticular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis 2013: published online 2 September 2013, doi: 10.1136/annrheumdis-2013-203582 4. Rosenbaum JT, Smith JR. Anti-TNF therapy for eye involvement in spondyloarthropathy. Clin Exp Rheumatol 2002;20(6 Suppl 28):S143-5 5. Hamideh F, Prete PE. Ophthalmologic manifestations of rheumatic diseases. Semin Arthritis Rheum 2001;30:217-41 6. Zeboulon N, Dougados M, Gossec L. Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis 2008;67:955-9 7. Vander Cruyssen B, Ribbens C, Boonen A, et al. The epidemiology of ankylosing spondylitis and the commencement of anti-TNF therapy in daily rheumatology practice. Ann Rheum Dis 2007;66:1072-7 8. Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187-93 9. Pato E, Ban˜ares A, Jover JA, et al. Undiagnosed spondyloarthropathy in patients presenting with anterior uveitis. J Rheumatol 2000;27:2198-202 10. Ferna´ndez-Melo´n J, Mun˜oz-Ferna´ndez S, Hidalgo V, et al. Uveitis as the initial clinical manifestation in patients with spondyloarthropathies. J Rheumatol 2004;31:524-7 11. Derhaag PJ, van der Horst AR, de Waal LP, Feltkamp TE. HLA-B27þ acute anterior uveitis and other antigens of the major histocompatibility complex. Invest Ophthalmol Vis Sci 1989;30:2160-4 12. Wendling D. Uveitis in seronegative arthritis. Curr Rheumatol Rep 2012;14:402-8 13. Schiffman RM, Jacobsen G, Whitcup SM. Visual functioning and general health status in patients with uveitis. Arch Ophthalmol 2001;119:841-9 14. Kirson NY, Rao S, Eldar-Lissai A, et al. Impact of extra-articular manifestations (EAMs) on medical resource utilization and cost of care for ankylosing spondylitis (AS) patients [abstract]. Ann Rheum Dis 2011;70(Suppl 3):428 15. Hajj-Ali RA, Lowder C, Mandell BF. Uveitis in the internist’s office: are a patient’s eye symptoms serious? Cleve Clin J Med 2005;72:329-39 16. Santos Lacomba M, Marcos Martı´n C, Gallardo Galera JM, et al. Aqueous humor and serum tumor necrosis factor-a in clinical uveitis. Ophthalmic Res 2001;33:251-5 17. Braun J, Bollow M, Neure L, et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995;38:499-505

! 2014 Informa UK Ltd www.cmrojournal.com

December 2014

18. Lindstedt EW, Baarsma GS, Kuijpers RW, van Hagen PM. Anti-TNF-alpha therapy for sight threatening uveitis. Br J Ophthalmol 2005;89:533-6 19. Levy-Clarke G, Jabs DA, Read RW, et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology 2014;121:785-96 20. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 2005;52: 2447-51 21. Rudwaleit M, Rødevand E, Holck P, et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis 2009;68:696-701 22. Guignard S, Gossec L, Salliot C, et al. Efficacy of tumor necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis 2006;65:1631-4 23. Horst-Bruinsma IE, van Denderen JC, Visman I, et al. Decreased recurrence rate of anterior uveitis in ankylosing spondylitis treated with adalimumab: an interim analysis [abstract]. Arthritis Rheum 2010;62(Suppl 10):1933 24. Lim LL, Fraunfelder FW, Rosenbaum JT. Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 2007;56:3248-52 25. Wendling D, Paccou J, Berthelot J-M, et al. New onset of uveitis during antitumor necrosis factor treatment for rheumatic diseases. Semin Arthritis Rheum 2011;41:503-10 26. Sieper J, Koenig A, Baumgartner S, et al. Analysis of uveitis rates across all etanercept ankylosing spondylitis clinical trials. Ann Rheum Dis 2010;69:226-9 27. Fiorelli VM, Bhat P, Foster CS. Nonsteroidal anti-inflammatory therapy and recurrent acute anterior uveitis. Ocul Immunol Inflamm 2010;18:116-20 28. Dougados M, Berenbaum F, Maetzel A, Amor B. Prevention of acute anterior uveitis associated with spondyloarthropathy induced by salazosulfapyridine [in French]. Rev Rhum Ed Fr 1993;60:81-3 29. Benitez-Del-Castillo JM, Garcia-Sanchez J, Iradier T, Ban˜ares A. Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis. Eye 2000;14:340-3 30. Mun˜oz-Ferna´ndez-Melo´n S, Hildago V, Ferna´ndez-Melo´n J, et al. Sulfasalazine reduces the number of flares of acute anterior uveitis over a one-year period. J Rheumatol 2003;30:1277-9 31. Berg IJ, Semb AG, van der Heijde D, et al. Uveitis is associated with hypertension and atherosclerosis in patients with ankylosing spondylitis: a crosssectional study. Semin Arthritis Rheum 2014: published online 20 May 2014, doi: 10.1016/j.semarthrit.2014.05.017 32. Bonafede M, Fox KM, Watson C, et al. Treatment patterns in the first year after initiating tumor necrosis factor blockers in real-world settings. Adv Ther 2012;29:664-74 33. Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005;123:903-12 34. Diaz-Llopis M, Garcı´a-Delpech S, Salom D, et al. Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther 2008;24:351-61 35. Perez-Alvarez R, Pe´rez-de-Lis M, Ramos-Casals M; BIOGEAS study group. Biologics-induced autoimmune diseases. Curr Opin Rheumatol 2013;25:56-64 36. Wendling D, Prati C. Paradoxical effects of anti-TNF-a agents in inflammatory diseases. Expert Rev Clin Immunol 2014;10:159-69

Uveitis risk in anti-TNF-naı¨ve ankylosing spondylitis Wendling et al.

2521

Comparing the risk of developing uveitis in patients initiating anti-tumor necrosis factor therapy for ankylosing spondylitis: an analysis of a large US claims database.

To compare the risk of developing uveitis in patients initiating anti-tumor necrosis factor (anti-TNF) agents (adalimumab, etanercept, and infliximab)...
439KB Sizes 5 Downloads 11 Views