Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis

Objectives The objective of this study was to examine the effectiveness and drug tolerability of biological DMARD (bDMARD) and Janus kinase inhibitor (JAKi) monotherapy in patients with RA in a multicentre cohort study.Methods Patients with RA for whom bDMARD/JAKi monotherapy without conventional synthetic DMARDs has been initiated were included. Monotherapy regimens were categorized as IL-6 receptor inhibitors (IL-6Ris), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKis, or TNF inhibitors (TNFis). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the DAS in 28 joints using ESR (DAS28)-ESR at 24 weeks, and drug retention was compared between monotherapy groups using IPW Cox proportional hazards models.Results A total of 849 treatment courses were included, involving 635 patients (IL-6Ris, 218; CTLA4Ig, 183; JAKis, 92; TNFis, 356). The change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than in the TNFi group, while those of the CTLA4Ig and JAKi groups were similar to that of the TNFi group [-0.20 (-0.48 to 0.08), -0.25 (-0.67 to 0.16), respectively]. IL-6Ri use was associated with significantly lower overall drug discontinuation than that for TNFi use [hazard ratio = 0.55 (0.39-0.78), P = 0.001]. Similar retention rates were identified for the CTLA4Ig and JAKi groups to that of the TNFi group.Conclusion In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi and TNFi monotherapy. Graphical Abstract