Comparative Risk of Cardiovascular Events with Biologic and Synthetic Disease-Modifying Anti-Rheumatic Drugs in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor-α inhibitors (TNFi), non-TNFi biologic and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA).Through 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 (OR) and 95% confidence interval (CI).

As compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR, 0.59 [0.34-1.00]), whereas csDMARDs were associated with increased risk of MACE (csDMARDs, including methotrexate: OR, 1.45 [1.09-1.93]; without methotrexate: OR, 2.57 [1.32-5.00]), without heterogeneity (I² =0%); there was no difference in risk of MACE between abatacept and TNFi (OR, 0.89 [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 increased risk of stroke (OR, 1.17 [1.01-1.36]); there was no difference in risk of stroke between different biologics (tocilizumab vs. TNFi: OR, 0.98 [0.59-1.61]; abatacept vs. TNFi: OR, 1.08 [0.86-1.34]; tocilizumab vs. abatacept: OR, 0.73 [0.39-1.38]), without heterogeneity (I² =0%). No comparative studies on cardiovascular risk with tofacitinib were identified.

Based on meta-analysis, as compared to TNFi, tocilizumab may be associated with reduced risk of MACE, whereas csDMARDs may be associated with increased risk of MACE and stroke.