Sustained efficacy of second-line JAK inhibitors in patients with rheumatoid arthritis: insights from the ANSWER cohort.

Abstract

This multicentre, retrospective study aimed to evaluate differences in drug continuation rates and efficacy between first- and second-line use of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) after failure of the initial therapy in real-world RA settings. Data from an observational multicentre registry of patients with RA in Japan were analysed, encompassing 5900 treatment courses (4046 bDMARD/JAKi-naïve cases and 1854 second-line cases). Gray's tests were used to compare the cumulative incidence function (CIF) for drug discontinuation, considering discontinuation due to remission as a competing risk. Competing risk analysis using Fine-Gray model was conducted to analyse the hazard ratios after adjusting for potential confounders. Changes in the Clinical Disease Activity Index (ΔCDAI) and disease activity score (ΔDAS28-CRP) were assessed at each time point compared with baseline using a linear mixed model with covariate adjustments. Among the TNF inhibitors, IL-6 inhibitors, Cytotoxic T-lymphocyte associated protein 4 (CTLA4) and JAKi, only JAKi showed no significant difference in CIF of first- and second-line treatments. Competing risk analysis showed that consistent with the CIF analysis, second-line treatment influenced the drug continuation rates for all drugs except for JAKi. In analysing CDAI and DAS28-CRP trends using a linear mixed model, JAKi demonstrated similar efficacy as first- and second-line therapy, unlike other drugs. JAKi maintained continuation rates and efficacy in second-line treatment compared with first-line treatment, which is potentially advantageous over bDMARDs for patients with RA who require a change in initial therapy.