Mode of action- and cause-specific drug retention of b/tsDMARDs in anti-SS-A antibody-positive rheumatoid arthritis: the ANSWER cohort study

Background To investigate drug retention by mode of action (MOA) and cause in rheumatoid arthritis (RA) patients with or without anti-SS-A antibodies using a multicenter registry. Methods We retrospectively analyzed the ANSWER cohort in Japan. Patients with RA who started or switched biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) between 2011 and 2024 and had baseline anti-SS-A antibody testing were included. Propensity score matching balanced baseline characteristics. Kaplan–Meier and competing risk analyses were conducted, and hazard ratios (HRs) were estimated using Cox proportional hazards models. Results After matching, 507 treatment courses from 255 anti-SS-A antibody-positive and 1,014 from 628 antibody-negative patients were analyzed. Anti-SS-A antibody positivity was not associated with overall b/tsDMARD retention (HR 1.07, 95% CI 0.91–1.26, p = 0.382). In MOA-stratified analyses, positivity showed a trend toward increased discontinuation with IL-6 receptor inhibitors and CTLA4-Ig. In cause-specific analyses, discontinuation due to adverse events was significantly more frequent in antibody-positive patients (HR 1.72, 95% CI 1.23–2.42, p = 0.002). Among adverse event-related discontinuations, positivity was associated with higher risks with IL-6 receptor inhibitors (HR 2.39, 95% CI 1.21–4.69, p = 0.01) and TNF inhibitors (HR 1.87, 95% CI 1.11–3.14, p = 0.02), but not with CTLA4-Ig or JAK inhibitors. Conclusion Anti-SS-A antibody-positive RA patients had greater risk of discontinuation due to adverse events, particularly with IL-6 receptor inhibitors and TNF inhibitors. These findings underscore the importance of considering MOA and discontinuation causes when selecting therapies.