Abstract
Objective To examine the comparative effects of biologic disease-modifying antirheumatic drugs (bDMARD) and tofacitinib against conventional synthetic DMARD (csDMARD) on incident cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).
Methods RA patients with ≥ 1 year of participation in the FORWARD study, from 1998 through 2017, were assessed for incident composite CVD events (myocardial infarction, stroke, heart failure, and CVD-related death validated from hospital/death records). DMARD were categorized into 7 mutually exclusive groups: (1) csDMARD-referent; (2) tumor necrosis factor-α inhibitor (TNFi); (3) abatacept (ABA); (4) rituximab; (5) tocilizumab; (6) anakinra; and (7) tofacitinib. Glucocorticoids (GC) were assessed using a weighted cumulative exposure model, which combines information about duration, intensity, and timing of exposure into a summary measure by using the weighted sum of past oral doses (prednisolone equivalent). Cox proportional hazard models were used to adjust for confounders.
Results During median (IQR) 4.0 (1.7–8.0) years of follow-up, 1801 CVD events were identified in 18,754 RA patients. The adjusted model showed CVD risk reduction with TNFi (HR 0.81, 95% CI 0.71–0.93) and ABA (HR 0.50, 95% CI 0.30–0.83) compared to csDMARD. While higher GC exposure as weighted cumulative exposure was associated with increased CVD risk (HR 1.15, 95% CI 1.11–1.19), methotrexate (MTX) use was associated with CVD risk reduction [use vs nonuse HR 0.82, 95% CI 0.74–0.90, and high dose (> 15 mg/week) vs low dose (≤ 15 mg/week) HR 0.83, 95% CI 0.70–0.99].
Conclusion ABA and TNFi were associated with decreased risk of CVD compared to csDMARD. Minimizing GC use and optimizing MTX dose may improve cardiovascular outcomes in patients with RA.
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