Biologics for rheumatoid arthritis: an overview of Cochrane reviews

Abstract

BACKGROUND:The biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies.OBJECTIVES: To compare the efficacy and safety of abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab in patients with RA.METHODS: This 'Overview of Reviews' was done by including all Cochrane Reviews on Biologics for RA available in The Cochrane Library. We included only data on standard dosing regimens for these biologic DMARDs from placebo-controlled trials. The primary efficacy and safety outcomes were ACR50 and withdrawals due to adverse events. We calculated Risk Ratios (RR) for efficacy, Odds Ratio (OR) for safety and combined estimates of events across the placebo groups as the expected Control Event Rate (CER). Indirect comparisons of biologics were performed for efficacy and safety using a hierarchical linear mixed model incorporating the most important study level characteristic (i.e. type of biologic) as a fixed factor and study as a random factor; reducing the between study heterogeneity by adjusting for the interaction between the proportion of patients responding on placebo and the duration of the trial.MAIN RESULTS: From the six available Cochrane reviews, we obtained data from seven studies on abatacept, eight on adalimumab, five on anakinra, four on etanercept, four on infliximab, and three on rituximab. The indirect comparison estimates showed similar efficacy for the primary efficacy outcome for all biologics with three exceptions. Anakinra was less efficacious than etanercept with a ratio of RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra was less efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023); and likewise adalimumab was more efficacious than anakinra, 2.34 (1.32 to 4.13; P = 0.003). In terms of safety, adalimumab was more likely to lead to withdrawals compared to etanercept, with a ratio of ORs of 1.89 (1.18 to 3.04; P = 0.009); anakinra more likely than etanercept, 2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept less likely than infliximab, 0.37 (0.19 to 0.70; P = 0.002).AUTHORS' CONCLUSIONS: Based upon indirect comparisons, anakinra seemed less efficacious than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer withdrawals due to adverse events than adalimumab, anakinra and infliximab. Significant heterogeneity in characteristics of trial populations imply that these finding must be interpreted.

Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis

“…Environmental and genetic factors are two major aspects of RA and account for approximately 60% and 40% of the risk for developing RA, respectively [2]. Although the mechanism underlying RA remains unknown, fibroblast-like synoviocytes (FLS) have been reported to play a critical role in the pathogenesis of RA [3, 4]. In the normal synovium, FLS are a highly differentiated unicellular cell type, governing the provisions of support, nourishment, and lubrication of the joint tissue [5].…”

Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors

“…Despite some variation attributable to these factors, estimates derived from randomized, controlled trials (RCTs) suggest that between 40% and 50% [7] of RA patients treated for at least 6 months with one of the three first-generation TNF-α inhibitors (etanercept, adalimumab and infliximab) failed to achieve the American College of Rheumatology 50% (ACR50) improvement criteria [8], while the results from a large, registry-based study [9] indicated that over 70% of these patients fail to achieve Disease Activity Score 28 joint count (DAS28)-defined "remission" (DAS28 <2.6).…”

Interpreting trial results following use of different intention-to-treat approaches for preventing attrition bias: a meta-epidemiological study protocol

“…The exponential family comprises many of the elementary discrete and continuous distributions. The analyses will be performed using the GLIMMIX procedure in SAS (V.9.2; SAS Institute Inc, Cary, North Carolina, USA) 60. The syntax is similar to that of the MIXED procedure and includes CLASS, MODEL and RANDOM statements.…”