Real-World Comparative Effectiveness of Sarilumab Versus Janus Kinase Inhibitors as Monotherapy in Rheumatoid Arthritis

Background Sarilumab (SAR), an interleukin-6 receptor inhibitor, and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real world evidence for MTX-free monotherapy remains limited. Methods We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1 to 1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3  ≥  third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. Results Across matched strata by prior b/tsDMARDs, retention and CDAI change were similar between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs) related discontinuation was higher with JAKi, yielding lower AEs specific retention. Both groups demonstrated GC sparing over time, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent. Conclusion In MTX-free monotherapy, SAR and JAKi achieved comparable 12 month retention and disease control. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds.