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

Objective We performed a systematic review and meta‐analysis to evaluate the comparative effects of tumor necrosis factor inhibitors ( TNF i), non‐ TNF i biologics, and conventional synthetic disease‐modifying antirheumatic drugs (cs DMARD s) 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 TNF i, non‐ TNF i biologics, tofacitinib, or cs DMARD s, 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 ( OR s) and 95% confidence intervals (95% CI s). Results As compared to TNF i, tocilizumab was associated with a decreased risk of MACE ( OR 0.59 [95% CI 0.34–1.00]), whereas cs DMARD s were associated with an increased risk of MACE (cs DMARD s including methotrexate OR 1.45 [95% CI 1.09–1.93]; without methotrexate OR 2.57 [95% CI 1.32–5.00]), without heterogeneity (I 2 = 0%); there was no difference in risk of MACE between abatacept and TNF i ( 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 TNF i, cs DMARD s 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 TNF i OR 0.98 [95% CI 0.59–1.61]; abatacept versus TNF i OR 1.08 [0.86–1.34]; tocilizumab versus abatacept OR 0.73 [95% CI 0.39–1.38]), without heterogeneity (I 2 = 0%). No comparative studies on cardiovascular risk with tofacitinib were identified. Conclusion Based on meta‐analysis, as compared to TNF i, tocilizumab may be associated with a reduced risk of MACE , whereas cs DMARD s may be associated with an increased risk of MACE and stroke.