Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis—the ANSWER cohort study

Abstract Objectives This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic DMARDs in patients with elderly-onset rheumatoid arthritis (EORA). Methods Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at age 60 or over. To adjust confounding factors by indication for initiation of TNF inhibitors (TNFi), IL-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events and remission were analysed as secondary outcomes. Results A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (hazard ratio [HR] = 0.38; 95% CI: 0.27, 0.55; P < 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with JAKi (HR = 0.38; 95% CI: 0.22, 0.66; P < 0.01) and IL-6i (HR = 0.29; 95% CI: 0.19, 0.46; P < 0.01) as compared with TNFi although CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse events was higher for JAKi (HR = 2.86; 95% CI: 1.46, 5.59; P < 0.01) than for TNFi. Conclusion In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.