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

Gulsen Ozen, Sofia Pedro, Kaleb Michaud

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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-a 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.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalJournal of Rheumatology
Issue number5
StatePublished - May 1 2021


  • Biologics
  • Cardiovascular
  • Cohort study
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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