Mode of action-specific and cause-specific retention of biologic and targeted synthetic disease-modifying antirheumatic drugs in anti-SS-A antibody-positive rheumatoid arthritis: The ANSWER cohort study.

Anti-SS-A (Ro) antibody-positive rheumatoid arthritis (RA) constitutes a clinically important subgroup, but its impact on retention of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) across different modes of action (MOA) and reasons for discontinuation remains unclear. We conducted a multicenter retrospective analysis of the Japanese ANSWER cohort, including RA patients who started or switched b/tsDMARDs between 2011 and 2024 and had baseline anti-SS-A antibody testing. Among 1,452 patients (2,703 treatment courses), 255 patients (17.6%) were anti-SS-A antibody positive (507 courses, 18.8%). Propensity score matching balanced baseline characteristics, and drug retention was evaluated using Kaplan-Meier and competing risk analyses. Overall discontinuation was analyzed using Cox proportional hazards models, and Fine-Gray subdistribution hazards models were used for discontinuation by reason and for adverse event-related discontinuation stratified by MOA. After matching, 507 treatment courses from 255 anti-SS-A antibody-positive patients and 1,014 courses from 628 antibody-negative patients were analyzed. Anti-SS-A antibody positivity was not associated with overall b/tsDMARD retention (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.91-1.26, p = 0.382). In MOA-stratified analyses, positivity showed a trend toward increased discontinuation with interleukin-6 (IL-6) receptor inhibitors and cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig). In competing-risk analyses, discontinuation due to adverse events was significantly more frequent in antibody-positive patients (subdistribution hazard ratio [sHR] 1.80, 95% CI 1.28-2.52; p = 0.000685). Among adverse event-related discontinuations, anti-SS-A antibody positivity was associated with higher risks with IL-6 receptor inhibitors (sHR 2.41, 95% CI 1.24-4.71; p = 0.0098) and tumor necrosis factor (TNF) inhibitors (sHR 2.04, 95% CI 1.22-3.40; p = 0.0066), but not with CTLA4-Ig or Janus kinase (JAK) inhibitors. These findings suggest that treatment tolerability, rather than overall efficacy, may be a key determinant of b/tsDMARD survival in anti-SS-A antibody-positive RA and that MOA- and cause-specific profiles should be considered when selecting therapies in this subgroup.