The risk of cardiovascular events associated with disease-modifying antirheumatic drugs in rheumatoid arthritis

Objective: To examine the comparative effects of biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib against conventional synthetic (cs) DMARDs on incident cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).

Methods: RA patients with ≥1-year participation in FORWARD 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). DMARDs were categorized into 7 mutually exclusive groups: (1) csDMARDs-referent (2) TNFi (3) Abatacept (4) Rituximab (5) Tocilizumab (6) Anakinra (7) Tofacitinib. Glucocorticoids were assessed using a weighted cumulative exposure (WCE) 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, 1,801 CVD events were identified in 18,754 RA patients. The adjusted model showed CVD risk reduction with TNFi (HR 0.82 [95% CI 0.72-0.94]) and abatacept (HR 0.50 [95% CI 0.30-0.83]) compared to csDMARDs. While higher glucocorticoid exposure as WCE was associated with CVD risk increase (HR 1.15 [95% CI 1.11-1.19]), methotrexate use was associated with CVD risk reduction (use vs. non-use: HR 0.82 [95% CI 0.74-0.90] and high-dose[>15mg/week] vs. lowdose[≤ 15mg/week]: HR 0.83 [95% CI 0.70-0.99]).

Conclusion: Abatacept and TNFi were associated with decreased risk of CVD compared to csDMARDs. Minimizing glucocorticoid use and optimizing MTX dose may improve CV outcomes in patients with RA.