Cardiovascular Risk in Rheumatoid Arthritis: Comparing TNF-α Blockade with Nonbiologic DMARDs

BACKGROUND: Elevated tumor necrosis factor (TNF)-alpha likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-alpha blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD). METHODS: Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-alpha blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months. RESULTS: We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-alpha blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-alpha blocking agents. The hazard ratio (HR) for the TNF-alpha blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-alpha blocking agents was strongest among individuals >= 65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction 0.075). CONCLUSION: Among subjects with rheumatoid arthritis, TNF-alpha blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis. (C) 2013 Elsevier Inc. All rights reserved.