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

Abstract

The objective of this study was to evaluate the relative efficacy of targeted immune modulators (TIMs) in TIM-naïve/mixed populations (≤\u200920% TIM-experienced) and TIM-experienced (>\u200920% TIM-experienced) adults with moderate-to-severe rheumatoid arthritis with an inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs (cDMARDs). A fixed-effects Bayesian network meta-analysis (NMA) was performed using published study-level data from 41 randomized controlled trials (RCTs) identified from two recent systematic literature reviews conducted by the Institute for Clinical and Economic Review, and two additional phase III trials for filgotinib (FINCH-1, FINCH-2). RCTs that compared TIMs with each other, cDMARD therapy, or placebo were included. Treatments included Janus kinase (JAK) inhibitors, tumor necrosis factor α inhibitors (TNFi), and other non-TNFi therapies. Efficacy was defined as achieving remission with a DAS28 score\u2009<\u20092.6 at 12 and 24 weeks. In the 12-week analysis for the TIM-naïve/mixed population, all TIMs combined with cDMARD therapy were significantly more likely to achieve remission compared with a cDMARD alone, 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 with cDMARD therapy. Similar trends were observed for the analyses on monotherapy or TIM-experienced population. This NMA demonstrated that tocilizumab is associated with a greater likelihood of remission (DAS28\u2009<\u20092.6) at 12 and 24 weeks compared with 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.