A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview

Abstract

Background: We sought 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 placebo-controlled trials that used standard dosing regimens. The major outcomes 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 were associated 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 other biologics, 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% CI 1.43-5.26).

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.

Figure 1

Flow chart for selection of systematic reviews included in the overview of systematic reviews of biologics for treatment of rheumatoid arthritis.

Figure 2

Comparison of each biologic to placebo for benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]). A value greater than 1.0 indicates a benefit from the biologic. CI = confidence interval. For details of studies included for each biologic, refer to Appendix 2 (avaiable at www.cmaj.ca/cgi/content/full/cmaj.091391/DC1).

Figure 3

Comparison of each biologic to placebo for safety (deterined by number of withdrawals because of adverse events). A value less than 1.0 indicates a benefit from the biologic. CI = confidence interval. For details of the studies included for each biologic, refer to Appendix 2 (avaiable at www.cmaj.ca/cgi/content/full/cmaj.091391/DC1).

Figure 4

Indirect comparison of each biologic to each other for benefit (ACR50). A value greater than 1.0 indicate a benefit from the biologic. CI = confidence interval. I² values for the studies are presented in Figure 2.

Figure 5

Indirect comparison of biologics to each other for safety (determined by number of withdrawals because of adverse events). A value greater than 1.0 indicate a benefit from the biologic. CI = confidence interval. I² values for the studies are presented in Figure 2.