Use of tumor necrosis factor–alpha inhibitors was associated with a significant reduction in the risk of coronary artery disease in patients with rheumatoid arthritis, particularly with longer term use of the drugs, in a retrospective cohort study.
The study of 2,101 patients with incident RA diagnosed during 2001-2011 showed that those treated with a tumor necrosis factor–alpha (TNF-alpha) inhibitor alone or with methotrexate had 55% lower relative risk (95% CI, 0.21-0.96) of coronary artery disease than did a reference group treated with non-methotrexate, nonbiologic, disease-modifying antirheumatic drugs (DMARDs).
Patients treated with methotrexate alone or in combination with other nonbiologic DMARDs showed a nonsignificant 46% reduction (95% CI, 0.27-1.09) in the incidence of coronary artery disease, compared with the reference group (Arthritis Care Res. 2014;66:355-63).
There were similar trends in reduction of the risk of cardiovascular disease (CVD, defined as a composite of coronary artery disease, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure), but these did not reach statistical significance. However, the authors suggested this and the methotrexate result may have been from inadequate power.
"These findings indicate that the benefits of TNF inhibitors may extend beyond their effects on joint disease and are associated with reduction in the leading comorbidity in RA, namely CVD," wrote Dr. Androniki Bili from Geisinger Medical Center, Danville, Pa., and her colleagues.
"These benefits should be considered when weighing the risks and benefits of using these costly medications in the treatment of RA," they wrote
Patients enrolled in the study had no history of CVD prior to treatment, and the model was adjusted for a range of confounders, including age, sex, race, smoking, blood pressure, diabetes, and other cardiovascular risk factors. Median follow-up was 3.4 years.
Patients taking TNF-alpha inhibitors for 16.1 months or more had a relative risk of 0.18 for coronary artery disease (95% CI, 0.06-0.50) and 0.31 for CVD (95% CI, 0.15-0.65). There was a similar but not statistically significant trend for use of methotrexate at 23.4 months.
Subgroup analysis showed that the incidence of coronary artery disease was even lower among patients without diabetes mellitus (hazard ratio, 0.39; 95% CI, 0.15-0.98) and among rheumatoid factor–positive patients (HR, 0.38; 95% CI, 0.15-0.95), compared with the reference group.
Rheumatoid arthritis is associated with increased cardiovascular morbidity, independent of traditional cardiovascular risk factors, that is thought to be partly mediated by chronic, systemic inflammation, the researchers said.
This has led to considerable interest in the potential of medication such as TNF-alpha inhibitors in reducing this risk, particularly in light of several observational studies suggesting a reduced risk of CVD among patients treated with methotrexate.
One author was coinvestigator on two AstraZeneca clinical trials in rheumatoid arthritis, but there were no other conflicts of interest declared.