To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients.


A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group.


There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21–0.96) for the aTNF group and 0.54 (95% CI 0.27–1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06–0.50) and for CVD of 0.31 (95% CI 0.15–0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group.


Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.