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

Abstract Objectives This multicentre retrospective study aimed to evaluate differences in drug continuation rates and efficacy between first- and second-line use of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) after failure of the initial therapy in real-world rheumatoid arthritis (RA) settings. Methods Data from an observational multicentre registry of patients with RA in Japan were analysed, encompassing 5,900 treatment courses (4,046 bDMARD/JAKi-naïve cases and 1,854 s-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. Results Among the TNF inhibitors, interleukin (IL)-6 inhibitors, 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 DAS-28 CRP trends using a linear mixed model, JAKi demonstrated similar efficacy as first- and second-line therapy, unlike other drugs. Conclusions JAKi maintained continuation rates and efficacy in second-line treatment compared with first-line treatment, potentially advantageous over bDMARDs for patients with RA who require a change in initial therapy.