Impact of Rheumatoid Arthritis Treatment Classes on Cardiovascular, Thromboembolic, Cancer Outcomes, and All-Cause Mortality: A Population-Based Cohort Study

Background: Rheumatoid arthritis (RA) is linked to increased risks of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancy, and mortality. However, differences in these risks by treatment class—particularly among older adults with cardiovascular (CVD) risk factors—remain unclear. Methods: We conducted a population-based cohort study using Ontario administrative data. Patients aged ≥67 years with incident RA (2008–2013) were followed through 2023. Outcomes included healthcare utilization for MACE and VTE, all-cause mortality, and cancer-related encounters. Time-varying treatment groups were: no csDMARD/advanced therapy (AT), glucocorticoids (GC) only, csDMARDs (reference), and biologic/targeted synthetic DMARDs (b/tsDMARDs). Weighted Fine–Gray models within a marginal structural framework were used, stratified by baseline CVD risk. Results: Among 10,058 patients, 80% had high CVD risk. Compared with csDMARDs, untreated patients (SHR 15.0; 95% CI 13.8–16.2) and GC users (SHR 1.29; 95% CI 1.13–1.47) had higher MACE risk, while AT use was associated with lower risk (SHR 0.53; 95% CI 0.37–0.77). Similar patterns were observed in low-risk patients. AT use was not associated with VTE. Untreated and GC users had increased mortality, whereas AT use reduced mortality. Increased cancer-related utilization was observed only in untreated patients. Conclusion: Treatment type strongly influences major outcomes in older adults with RA, underscoring the importance of integrating CVD and thrombotic risk into therapeutic decisions.