Objective. To assess the comparative efficacy of targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and biologics, approved and reimbursed in Russia to treat adults with active rheumatoid arthritis (RA), using a systematic review and network meta-analysis of randomized clinical trials (RCTs).

Material and methods. We conducted a systematic search for RCTs evaluating the efficacy of biologics (adalimumab, golimumab, levilimab, olokizumab, sarilumab, tocilizumab, infliximab, rituximab, certolizumab pegol, abatacept and etanercept) and tsDMARDs (tofacitinib, baricitinib and upadacitinib), both in combination with conventional synthetic DMARDs (csDMARDs) and in monotherapy for the treatment of adults with active RA. Efficacy was assessed with ACR20/50/70 criteria, DAS28 remission rate (RR) and DAS28 low disease activity (LDA) at 12 and 24 weeks of therapy. We performed Bayesian network meta-analyses based on the Monte-Carlo simulation. We ranked the treatment options based on the surface under the cumulative ranking curve values. Additionally, we performed analysis by class and a series of sensitivity analyses to evaluate efficacy at 24 weeks of treatment.

Results. The proportion of patients with an inadequate response to previous methotrexate therapy was at least 50% in the included RCTs. All analysed drugs in combination with csDMARDs were superior to csDMARDs and placebo. There were no statistically significant differences in efficacy between biologics and targeted synthetic DMARDs at 12 weeks. IL-6 inhibitors olokizumab (Q2W and Q4W) and levilimab occupied the top three ranks in ACR20/50/70 and DAS28 LDA at 12 weeks and retained high positions at 24 weeks. Tocilizumab showed the highest rank in the analysis for the DAS28 RR. Network meta-analyses confirmed that adding csDMARDs to biologics increases their efficacy.

Conclusion. Given the predominantly comparable relative effectiveness of the analyzed drugs, health professionals should also consider other factors, when choosing a treatment option for adults with active RA.