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A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview
Jasvinder A. Singh MD, Robin Christensen PhD, George A. Wells PhD, Maria E. Suarez-Almazor MD, Rachelle Buchbinder MD, Maria Angeles Lopez-Olivo MD, Elizabeth Tanjong Ghogomu MD, Peter Tugwell MD
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Background: Wesought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheumatoid arthritis. Methods: In this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebocontrolled trials that used standard dosing regimens. The majoroutcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics. Results: Compared with placebo, biologics wereassociated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62–4.29) and a number needed to treat for benefit of 4 (95% CI 4–6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13–1.71), with a number needed to treat for harm of 52 (95% CI 29–152). Anakinra was less effective than all of the otherbiologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21– 0.99) and etanercept (OR 0.34, 95% CI 0.14–0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18–3.04; anakinra OR 2.05, 95% CI 1.27–3.29; and infliximab OR 2.70, 95% CI1.43–5.26). Interpretation: Given the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.

In the last decade,several biologics have been approved, and their use has revolutionized the treatment of rheumatoid arthritis. These biologics are targeted therapies that dramatically inhibit the progression of joint damage in rheumatoid arthritis. These include inhibitors of tumour necrosis factor5 (infliximab, etanercept, adalimumab, certolizumab and golimumab), anti-interleukin 1 therapy (anakinra), anti-CD28therapy (abatacept) and anti–B-cell therapy (rituximab). Biologics are recommended for use in patients with rheumatoid arthritis who have a suboptimal response or intolerance to traditional disease-modifying antirheumatic drugs, such as methotrexate. Although biologics have typically been compared with placebo, with both groups taking the same dose of methotrexate concomitantly, there have been nolarge randomized controlled trials comparing the biologics to one another. One randomized controlled trial included 2 biologics but compared both only to placebo and not to each other.6 Because of the high cost of biologics, different routes and administration schedules and different adverse event profiles, general practitioners and rheumatologists need to know their relative benefits and safetywhen deciding on treatment. One previous systematic review compared the benefits and safety of biologics using data from randomized and nonrandomized controlled trials. This review combined both recommended and nonrecommended doses;7 it found only one difference: infliximab was superior to anakinra in achieving a 20% improvement in the American College of Rheumatology response criteria for...
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