OBJECTIVE
To assess the comparative efficacy of targeted disease-modifying antirheumatic drugs (DMARDs) and biologics, registered and reimbursed in the Russian Federation for the treatment of 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 (ADA), golimumab (GLM), levilimab (LVL), olokizumab (OKZ), sarilumab (SAR), tocilizumab (TCZ), infliximab (INF), rituximab (RTM), certolizumab pegol (CZP) abatacept (ABA) and etanercept (ETA)) and targeted synthetic DMARDs (tofacitinib (TOFA), baricitinib (BARI) and upadacitinib (UPA)), both in combination with standard synthetic DMARDs (mainly methotrexate (MTX)) and in monotherapy for the treatment of adults with active RA. Efficacy was assessed with ACR20/50/70 criteria, DAS28 remission rate and DAS28 low disease activity at 12 and 24 weeks of therapy. We performed an evidence synthesis with Bayesian meta-analysis based on the Monte Carlo method. We ranked the treatment options based on the SUCRA (surface under the cumulative ranking curve) values. Additionally, we performed analysis by class and a series of sensitivity analyses to evaluate efficacy after 24 weeks of therapy.
RESULTS
We included in the network only the studies with the proportion of patients with an inadequate response to previous MTX therapy more than 50%. All analysed drugs in combination with DMARDs were superior to DMARDs and placebo. According to the results of the analysis after 12 weeks of therapy, there were no statistically significant differences in efficacy between biologics and targeted synthetic DMARDs. IL-6 inhibitors: OKZ (once every 2 weeks and once every 4 weeks) and LVL occupied the first three ranks in ACR20/50/70 and DAS28 low disease activity at 12 weeks and retained high results at 24 weeks of therapy. TCZ showed the highest rank in the analysis for the DAS28 remission rate. Network meta-analysis confirmed that adding DMARDs to biologics increases their efficacy.
CONCLUSION
Given the predominantly comparable efficacy of the analyzed drugs, health professionals should consider safety profile, dosage regimens, routes of administration, patient comorbidities and preferences, costs of the healthcare system, etc., when choosing a treatment option for adult patients with active RA.
