Comparative effectiveness and safety of sarilumab vs Janus kinase inhibitors in late- and younger-onset rheumatoid arthritis.

Abstract

Glucocorticoid (GC)- and methotrexate (MTX)-sparing strategies are clinically important in rheumatoid arthritis (RA), yet comparative real-world evidence for sarilumab (SAR) vs Janus kinase inhibitors (JAKi) is limited. Whether treatment effects differ by age at onset-late-onset RA (LORA) vs young-onset RA (YORA)-also remains unclear. This study aimed to compare the effectiveness and safety of sarilumab and JAK inhibitors in patients with late- and younger-onset rheumatoid arthritis. We conducted a multicentre real-world cohort study of adults with RA initiating SAR or a JAKi. Outcomes over 12 months included change from baseline in MTX dose (ΔMTX, mg/week) and GC dose (ΔGC, mg/day), cumulative treatment discontinuation, and change in Clinical Disease Activity Index (CDAI). Analyses were performed within LORA and YORA strata, and propensity score matching (PSM) was applied separately in each stratum to balance baseline characteristics. Sensitivity analyses were conducted in the matched cohorts. Both SAR and JAKi were associated with progressive tapering of concomitant MTX and GC during follow-up. SAR was associated with a higher frequency of MTX discontinuation compared with JAKi. In contrast, GC discontinuation and CDAI improvement were broadly similar between treatments across age strata and MTX subgroups. Findings were consistent after PSM and in sensitivity analyses within both LORA and YORA. In routine clinical practice, SAR and JAKi support de-escalation of concomitant therapy. SAR may permit earlier MTX withdrawal without loss of disease control, with comparable GC tapering and disease activity improvement in both LORA and YORA.