JAKs Show Advantage in RA When Therapy Change Required
A retrospective multicenter study that focused on real-world clinical outcomes following initial therapy failure indicates that Janus kinase inhibitors (JAKi) may provide a clinical advantage for patients with rheumatoid arthritis (RA) who require transition from initial therapy.
The researchers investigated whether the effectiveness and continuation of biological disease-modifying antirheumatic drugs (bDMARDs) and JAKis differed when used as first- versus second-line therapies in treatment. The study drew on data from an observational registry of 5900 treatment courses, including 4046 from patients naïve to bDMARDs and JAKis and 1854 from those receiving second-line treatment.
The cumulative incidence function (CIF) for drug discontinuation was compared across treatment lines using Gray’s test; discontinuation due to remission was treated as a competing risk. The Fine–Gray competing risk model adjusted for potential confounding factors to assess hazard ratios. Changes in the Clinical Disease Activity Index (CDAI) and the disease activity score based on C-reactive protein (DAS28-CRP) were analyzed using a covariate-adjusted linear mixed model.
Findings revealed that among tumor necrosis factor (TNF) inhibitors, interleukin-6 (IL-6) inhibitors, cytotoxic T-lymphocyte-associated protein 4 (CTLA4) agents, and JAKi, only JAKi demonstrated no statistically significant difference in drug continuation rates between first- and second-line use. This pattern held in both CIF and competing risk analyses. Furthermore, JAKis maintained comparable efficacy between treatment lines in terms of CDAI and DAS28-CRP, unlike other bDMARDs, which demonstrated reduced performance in second-line settings.
Reference:
Tsujimoto K, Ebina K, Okamura S, et al. Sustained efficacy of second-line JAK inhibitors in patients with rheumatoid arthritis: insights from the ANSWER cohort. Rheumatology. 2025; 64(7): 4207–4217
