Comparative Efficacy (DAS28 remission) of Targeted Immune Modulators for Rheumatoid Arthritis: A Network Meta-Analysis

Abstract

Background The objective of the study was to evaluate the relative efficacy of targeted immune modulators (TIMs) in TIM-naïve/mixed (≤ 20% TIM-experienced) and TIM-experienced (> 20% TIM-experienced) adults with moderately-to-severe rheumatoid arthritis with an inadequate response or intolerance to conventional disease-modifying antirheumatic drugs (cDMARDs). Methods A fixed effects Bayesian network meta-analysis (NMA) was performed using published study-level data form 41 randomized controlled trials (RCTs), identified from 2 recent systematic literature reviews conducted by the Institute for Clinical and Economic Review, and 2 additional phase III trials for filgotinib (FINCH-1, FINCH-2). RCTs that compared TIMs to each other, cDMARD or placebo were included. Treatments included Janus kinase (JAK) inhibitors, tumor necrosis factor alpha inhibitors (TNFi), and other non-TNFis. Efficacy was defined as achieving remission with a DAS28 score < 2.6 at 12 and 24 weeks. Results In the 12-week analysis for the TIM-naïve/mixed population, all TIMs combined with cDMARD were more likely to achieve remission compared to cDMARD alone (statistically significant), with intravenous tocilizumab showing a substantially greater magnitude of effect (odds ratio = 19.36, 95% credible interval: 11.01, 38.16). Similarly, in the 24-week analysis, intravenous and subcutaneous tocilizumab showed the highest odds ratio of achieving DAS28 remission compared to cDMARD. Similar trends were observed for the analyses on monotherapy or TIM-experienced population. Conclusion This NMA demonstrated that tocilizumab is associated with a greater likelihood of remission (DAS28 < 2.6) at 12 and 24 weeks compared to most other TIMs including new JAK inhibitors, when used in combination with a cDMARD or as monotherapy, among TIM-naïve/mixed or TIM-experienced populations.