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

Abstract

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.

Comparing cardiovascular risk of patients with rheumatoid arthritis within the Social Security Disability Insurance with those commercially insured

“…We made efforts to account for disease activity in our study by using initiation of bDMARD or tsDMARD and to also determine the effect of b/tsDMARD in lowering CVD risk as formal disease activity measures were not available in these claims databases. The results of our study were consistent with previous data about this topic where there were no differences in the risk for CVD after we limited the study population (cohort 3) to those who initiated a new b/tsDMARD or switched to a new b/tsDMARD [ 14 ]. There is a likelihood that some patients with high disease activity remained only on csDMARD, but our results suggest that they likely initiated or switched b/tsDMARD.…”

Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events

“…Thus, the higher risk for CV events in autoantibody-positive RA may be related to a more severe and chronic course of the disease rather than direct effects of autoantibodies on the vessels. These data support the observations that effective control of inflammation may lower CV risk [ 31 , 32 ].…”

Rheumatoid Arthritis, as a Clinical Disease, but Not Rheumatoid Arthritis-associated Autoimmunity is Linked to Cardiovascular Events

“…Thus the higher risk for CV events in autoantibody-positive RA is likely related to a more severe and chronic course of the disease rather than direct effects of autoantibodies on the vessels. These data support the observations that effective control of in ammation may lower CV risk (30,31).…”