Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Academic Article


  • Objective: We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFi), non-TNFi biologics, and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA). Methods: Using a systematic search through May 8, 2018, we included 14 observational studies in adults with RA treated with TNFi, non-TNFi biologics, tofacitinib, or csDMARDs, reporting the risk of major adverse cardiovascular events (MACE) or stroke. Only studies reporting active comparators were included. We performed random effects meta-analysis and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: As compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR 0.59 [95% CI 0.34–1.00]), whereas csDMARDs were associated with an increased risk of MACE (csDMARDs including methotrexate OR 1.45 [95% CI 1.09–1.93]; without methotrexate OR 2.57 [95% CI 1.32–5.00]), without heterogeneity (I2 = 0%); there was no difference in risk of MACE between abatacept and TNFi (OR 0.89 [95% CI 0.71–1.11]), or between tocilizumab and abatacept (OR 0.81 [0.57–1.16]). Based on 11 cohorts (n = 135,053 patients), as compared to TNFi, csDMARDs were associated with an increased risk of stroke (OR 1.17 [95% CI 1.01–1.36]); there was no difference in risk of stroke between different biologics (tocilizumab versus TNFi OR 0.98 [95% CI 0.59–1.61]; abatacept versus TNFi OR 1.08 [0.86–1.34]; tocilizumab versus abatacept OR 0.73 [95% CI 0.39–1.38]), without heterogeneity (I2 = 0%). No comparative studies on cardiovascular risk with tofacitinib were identified. Conclusion: Based on meta-analysis, as compared to TNFi, tocilizumab may be associated with a reduced risk of MACE, whereas csDMARDs may be associated with an increased risk of MACE and stroke.
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    Author List

  • Singh S; Fumery M; Singh AG; Singh N; Prokop LJ; Dulai PS; Sandborn WJ; Curtis JR
  • Start Page

  • 561
  • End Page

  • 576
  • Volume

  • 72
  • Issue

  • 4