A. Diamantopoulos

AB0432 Efficacy of Biologic Treatments in Early Active Rheumatoid Arthritis: an Indirect Comparison

Background To date, no head-to-head trials have been conducted comparing the efficacy of biologic treatments for early active rheumatoid arthritis (ERA). Objectives To evaluate the effectiveness of tocilizumab (TCZ) compared with other traditional and biologic disease-modifying antirheumatic drugs (tDMARDs and bDMARDs), alone and in combination, in adult patients with moderate to severe ERA who have not been treated with methotrexate (MTX) or bDMARDs. Methods A literature review was undertaken to identify randomized controlled trials (RCTs) of tDMARDs and bDMARDs in patients with ERA (duration, <3 years) that reported efficacy outcomes, including the proportions of patients achieving American College of Rheumatology (ACR) scores of 20, 50, 70, and 90 and disease activity score (DAS28)–defined remission (DAS28<2.6). Study data were pooled using Bayesian network meta-analysis techniques. For ACR response, data were analyzed using a fixed-effects (FE) ordered probit model, which makes efficient use of ordered categorical data and guarantees coherent prediction of multinomial response probabilities. For DAS remission, data were analyzed with an FE binomial logit model. The analysis included only results for treatments in licensed doses. Sensitivity analyses tested the effects of grouping treatments by class and broadening and narrowing inclusion criteria. Results We included 16 RCTs of tDMARDs (MTX, sulfasalazine [SSZ], hydroxychloroquine [HCQ]), bDMARDs (abatacept [ABT], adalimumab [ADA], etanercept [ETN], infliximab [IFX], golimumab [GOL], and TCZ), and tofacitinib (Tofa). Results indicate that all bDMARDs+MTX, triple tDMARD therapies, and TCZ and Tofa in monotherapy significantly increased response across all ACR categories versus MTX (Figure). Probabilities of ACR response to bDMARDs+MTX were broadly similar, with no significant differences between agents. Probabilities of ACR response to bDMARDs in monotherapy were more varied, with a trend toward higher values for Tofa and TCZ than ETN or ADA. Only a subset of studies reported DAS remission. Results show that treatment with Tofa or any bDMARD (± MTX) except ADA alone improved the likelihood of DAS remission versus MTX. TCZ (± MTX) generated the highest probability of remission among bDMARD agents and was significantly more effective than all other bDMARDs (± MTX) and Tofa. Results across both outcomes were robust to alternative grouping of interventions and to change in the inclusion criteria. Figure 1. Median relative treatment effects vs MTX (95% credible interval). PRD, prednisone/prednisolone. Conclusions Based on ACR response, the expected efficacy of bDMARDs+MTX, Tofa and TCZ monotherapy, and triple tDMARD therapy appears comparable in early RA. TCZ and Tofa in monotherapy are more effective than ADA alone and likely to be more effective than ETN alone. TCZ ± MTX is expected to have the highest probability of generating DAS remission and is significantly better than other bDMARDs ± MTX and Tofa. Disclosure of Interest L. Sawyer Consultant for: Roche, S. Chang Consultant for: Roche, A. Diamantopoulos Consultant for: Roche, F. Dejonckheere Employee of: Roche DOI 10.1136/annrheumdis-2014-eular.2177

THU0308 Indirect comparison of ACR response of biologic treatments in active SJIA

Background To date, no biologic treatments other than tocilizumab (TCZ) have been approved in active Systemic Juvenile Idiopathic Arthritis (SJIA). Some however are used off label. Published evidence on their efficacy in SJIA is scarce, and there is no head-to-head data from randomised clinical trials (RCT) on the comparative efficacy of biologic treatments in SJIA. Objectives This analysis considers the current evidence on ACR responses of SJIA patients on biologics (used on and off label), synthesises this information, and explores efficacy differences. Methods A systematic literature review was conducted to identify RCTs that report ACR responses of SJIA patients on any biologic treatment, initially limited to SJIA, then extended to include any JIA subtype population. Reported ACR responses were compared with TCZ responses from the TENDER study,1 using an adjusted indirect comparison, comparing the relative risks of the clinical trials.2 The following outcomes were considered; ACR30 response with absence of fever, ACR30 response alone, ACR50, ACR70 and ACR90 response. Where needed, reported ACR responses were corrected to control for the differences in subtype disease. Results The initial literature review identified only one RCT with data on anakinra (ANK).3 The extension of the review yielded more results. However, only one additional study, with evidence on infliximab (INF), was deemed appropriate for comparison with TENDER, due to study design.4 The indirect comparison on ACR30 response without fever shows that patients on TCZ are more likely to achieve this outcome with TCZ than with ANK, although not statistically significant (RR=1.91; CI.: 0.84, 4.37). In ACR30 response alone the analysis shows statistical significance in favour of TCZ (RR=2.37 CI.: 1.10, 5.10). ACR50, 70 and 90 responses were not reported. In the comparison with INF, assuming no correction for the differences in the population subtype between the trials, patients treated with TCZ are also significantly more likely to reach ACR 30 response (RR=2.85 CI.: 1.38, 5.87), as well as ACR50 and ACR70 response. If a correction is applied the response with TCZ increases comparing to INF. ACR90 response was not reported. Conclusions There is a dearth of evidence in the literature to infer on efficacy differences across all biologics used for the treatment of SJIA patients. Based on the current evidence and the analysis conducted, patients on TCZ, the only approved biologic treatment for SJIA to date, are roughly 2-3 times more likely to achieve ACR response than if treated with ANK or INF. References De Benedetti F. Efficacy and Safety of Tocilizumab in Patients with SJIA: TENDER 52-Week Data. EULAR 2011 Bucher HC, Guyatt GH, Griffith LE et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683-91. Quartier P, Allantaz F, Cimaz R et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011;70:747–754. Ruperto N, Lovell DJ, Cuttica R et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007 Sep;56(9):3096-106. Disclosure of Interest A. Diamantopoulos Consultant for: Hoffman-La Roche, C. LeReun Consultant for: Hoffman-La Roche, R. Westhovens Consultant for: Hoffman-La Roche, F. Dejonckheere Employee of: Hoffman-LaRoche

MD2 ECONOMIC CONSEQUENCES OF PROVIDING RITUXIMAB AS ATREATMENT ALTERNATIVE FOR RHEUMATOID ARTHRITIS IN THE NETHERLANDS

prescription drug benefit program for the elderly instituted at the end of 2005 in the United States. METHODS: We implemented retrospective analyses of pharmacy claims of beneficiaries aged 67–79 years from 2005 to 2006, from a large pharmacy chain in the United States. Subjects aged 61–63 were used a control group in a differences-in-differences approach to account for trends not related to Part D. The final sample represented approximately 2.4 million unique beneficiaries aged 67–79. The main outcomes are: 1) Changes in proportion of total days of therapy dispensed as generics, and 2) changes in prescription utilization for each therapeutic class. RESULTS: Prescription drug use by these beneficiaries increased by 11% from 2005 to 2006. After adjustment for secular trends and other potential confounders, utilization of each therapeutic class was similar in 2005 and 2006. Small increases in drug utilization occurred for several drug classes, ranging from 0.66 pill days (0.46%) for users of nonsteroidal anti-inflammatories (NSAIDs) to 4.64 pill days (1.78%) for users of angiotensin-converting enzyme (ACE) inhibitors. Decreases occurred for anti-diabetic drugs (–2.06 pill days, –0.58%), betablockers (–1.24, –0.49%), and benzodiazepines (–5.96 pill days, –3.57%). Overall, beneficiaries were slightly less likely to fill prescriptions for generic drugs vs. brand-name drugs in 2006 compared to 2005 (OR 0.98, 95% CI 0.97–0.98). CONCLUSION: Small increases in prescription drug utilization occurred across numerous drug classes for these Medicare seniors following the implementation of the Medicare Part D Prescription Benefit, while overall market share by drug class did not change significantly. Further analyses are needed to explore the degree to which these changes reflect moral hazard versus beneficial expansions of coverage.