Abstract
Objective Methotrexate has been associated with reduced risk for cardiovascular disease (CVD) events among rheumatoid arthritis (RA) patients not exposed to biologic disease-modifying antirheumatic drugs (bDMARD). The effect of concomitant methotrexate on CVD risk among RA patients initiating bDMARDs remains unknown.
Methods A retrospective cohort study was conducted to assess the effect of methotrexate on CVD risk using 2006–2015 Medicare claims data for RA patients initiating bDMARDS. The main exposure was current use of methotrexate, updated in a time varying fashion. The primary outcome was a composite of incident myocardial infarction, stroke, and fatal CVD. Secondary outcomes were each event that comprised the primary outcome. Incidence rates (IR) and 95% confidence intervals (CI) were calculated using Poisson regression. Associations between methotrexate and risk of CVD were assessed using Cox regression.
Results A total of 88,255 bDMARD initiations and 1,861 CVD events were included in this study. Mean age was 64.6 (12.3) years, 84.0% female, 68.2% non-Hispanic white. The crude IRs for CVD were 17.9 (16.9–18.8) and 12.1 (95%CI: 11.1–13.2) per 1,000 patient-years among methotrexate unexposed and exposed, respectively. The multivariable adjusted HR for CVD events associated with methotrexate was 0.76 (0.68– 0.85). Multivariable adjusted HRs were 0.78 (0.66, 0.91), 0.74 (0.62, 0.88), 0.77 (0.68, 0.86), and 0.82 (0.73, 0.93) for MI, stroke, MI or stroke, and a composite CVD outcome. Results were robust in sensitivity and subgroup analyses.
Conclusion Among RA patients receiving biologics, concomitant methotrexate use was associated with a 24% lower risk for CVD events.