Major adverse cardiovascular events or venous thromboembolism in patients with rheumatoid arthritis initiating biological or targeted synthetic disease-modifying antirheumatic drugs: a nationwide, population-based cohort study

Background: Rheumatoid arthritis (RA) is complicated by a high risk of cardiovascular disease and requires the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for persistently active disease despite first-line therapies. The influence of b/tsDMARDs, especially tsDMARDs, on cardiovascular risk in Taiwanese patients with RA remains unclear.Objectives: To compare the risk of major cardiovascular adverse events (MACEs) or venous thromboembolism (VTE) amongst RA patients initiating approved b/tsDMARDs for up to 5 years.Design: A nationwide, population-based, retrospective cohort study.Methods: Using Taiwan National Health Insurance (NHI) Research Database, we identified patients with RA initiating NHI-reimbursed b/tsDMARDs indicated for RA between 2001 and 2020. Study outcomes were newly developed MACEs or VTE within 5 years of the first b/tsDMARD initiation. Time-dependent Cox regression analysis was performed to determine the association between b/tsDMARDs and MACEs or VTE and independently associated or protective factors. Subgroup analyses by age at b/tsDMARD initiation and cardiovascular risk levels, as well as sensitivity analyses of b/tsDMARD initiation after 2012, were performed.Results: We enrolled 12,332 adults with RA initiating the first b/tsDMARD during pre-determined period. The incidence rates of MACE and VTE were 894 and 283 per 100,000 person-years, respectively. After adjustment, other b/tsDMARDs were not associated with a higher risk of MACEs or VTE than tumour necrosis factor inhibitors (TNFis) up to 5 years after initiation. Subgroup analyses by age at b/tsDMARD initiation and cardiovascular risk levels revealed consistent findings. Factors associated with or protective against MACEs or VTE were identified.Conclusion: No non-TNFi b/tsDMARD had a higher risk of MACEs or VTE than TNFis up to 5 years after initiation amongst patients with RA, and this remained consistent for those initiating their b/tsDMARD at age 65 years and older or with high cardiovascular risk.