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Tocilizumab and the risk for cardiovascular disease: a direct comparison among biologic disease-modifying antirheumatic drugs for rheumatoid arthritis patients

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Xie F1,2, Yun H1,2, Levitan EB2, Muntner P2, Curtis JR1,2. Arthritis Care Res (Hoboken). 2018 Sep 3. doi: 10.1002/acr.23737. [Epub ahead of print]


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1 Division of Clinical Immunology and Rheumatology.

2 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.


BACKGROUND: Multiple studies have observed seemingly unfavorable changes in lipid profiles associated with IL6 receptor antagonists (IL-6R) and some other rheumatoid arthritis (RA) therapies. The real-world cardiovascular disease (CVD) risk associated with the first approved anti IL-6R medication for RA, tocilizumab, remains uncertain.

METHODS: A cohort study using 2006-2015 Medicare and MarketScan claims data was conducted, studying RA patients who initiated biologic disease-modifying antirheumatic drugs after January 1, 2010. The primary outcome was a composite of myocardial infarction, stroke, and fatal CVD, assessed using a validated method. The influence of potential confounding due to RA disease activity was assessed in a subgroup analysis (5-10% of biologic initiations) using the multi-biomarker disease activity (MBDA) score.

RESULTS: A total of 88,463 RA patients were included. The crude incidence rate (IR) per 1000 patient-years for composite CVD among Medicare patients ranged from 11.8 (95%CI: 9.7-14.4) for etanercept to 17.3 (15.2-19.7) for rituximab users. The crude incidence rate for pooled TNFi users was 15.0 (13.9-16.3). Compared to tocilizumab, the adjusted hazard ratios were 1.01 (0. 79-1.28) for abatacept, 1.16 (0.89-1.53) for rituximab, 1.10 (0.80-1.51) for etanercept, 1.33 (0.99-1.80) for adalimumab, and 1.61 (1.22-2.12) for infliximab. There were no statistically significant differences in CVD risk between tocilizumab and any other biologic using MarketScan data. Results were robust in numerous subgroup analyses and after external adjustment to control for RA disease activity in the subgroup of patients with linked MBDA test results (n=4,156).

CONCLUSION: Tocilizumab was associated with CVD risk comparable to etanercept, as well as a number of other RA biologics.