Scientific Publications by FDA Staff

Am J Med 2013 Aug;126(8):730

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

Solomon DH, Curtis JR, Saag KG, Lii J, Chen L, Harrold LR, Herrinton LJ, Graham DJ, Kowal MK, Kuriya B, Liu L, Griffin MR, Lewis JD, Rassen JA

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.