Comparative effectiveness and safety of five Janus kinase inhibitors in real-world clinical practice: the multicentre ANSWER cohort

OBJECTIVES: To compare treatment effectiveness and safety among five Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and to identify factors associated with treatment discontinuation in real-world clinical practice. METHODS: This retrospective multicentre study used data from the ANSWER cohort in Japan. RA treatment courses initiating tofacitinib, baricitinib, peficitinib, upadacitinib, or filgotinib between 2013 and 2025 were included. Treatment discontinuation due to ineffectiveness and adverse events was evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards models with multiple imputation. Analyses were adjusted for patient, disease, and treatment characteristics, including prior treatment history. RESULTS: A total of 1,798 treatment courses from 1,240 patients were analysed. Discontinuation risk due to ineffectiveness was lower with upadacitinib (HR 0.33, 95% CI 0.24 to 0.47) and filgotinib (HR 0.59, 95% CI 0.42 to 0.85) than with tofacitinib (reference), baricitinib (HR 0.82, 95% CI 0.63 to 1.06), and peficitinib (HR 1.23, 95% CI 0.89 to 1.70). Differences in discontinuation due to adverse events were observed only between upadacitinib (HR 0.57, 95% CI 0.38 to 0.85) and peficitinib (reference). Prior IL-6i or JAKi use increased ineffectiveness-related discontinuation for tofacitinib, baricitinib, and peficitinib, but not upadacitinib (IL-6i/JAKi: HR 0.67/1.14, 95% CI 0.38-1.16/0.65-1.98) or filgotinib (HR 0.83/1.38, 95% CI 0.45-1.53/0.72-2.65). CONCLUSIONS: Treatment effectiveness and safety differed among JAKi in real-world clinical practice. Upadacitinib and filgotinib were associated with higher treatment persistence, and the adverse impact of prior IL-6 inhibitor or JAKi exposure was not evident for these agents.