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.
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