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Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial

Author

Giles JT1, Sattar N2, Gabriel S3, Ridker PM4, Gay S5, Warne C6, Musselman D7, Brockwell L6, Shittu E6, Klearman M7, Fleming TR8. Arthritis Rheumatol. 2019 Aug 30. doi: 10.1002/art.41095. [Epub ahead of print]

Author Information

1 Division of Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY, United States.

2 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

3 Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States.

4 Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

5 Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.

6 Roche Products Ltd., Welwyn Garden City, United Kingdom.

7 Genentech, Inc., South San Francisco, CA, United States.

8 Department of Biostatistics, University of Washington, Seattle, WA, United States.

Abstract

OBJECTIVE: 

To compare the risk for major adverse cardiovascular events (MACE) in RA patients treated with tocilizumab versus the tumor necrosis factor inhibitor etanercept.

METHODS: 

This randomized, open-label, parallel-group trial enrolled patients with active seropositive RA (N=3080), inadequate responses to conventional synthetic disease-modifying antirheumatic drugs, and at least one cardiovascular risk factor. Patients were randomly assigned 1:1 to open-label tocilizumab 8 mg/kg/month or etanercept 50 mg/week and followed up for an average of 3.2 years. The primary end point was comparison of time-to-first MACE. The trial was powered to exclude a 1.8 or higher relative hazard of MACE for tocilizumab versus etanercept.

RESULTS: 

By week 4, serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were 11.1%, 5.7%, and 13.6% higher, respectively, for patients allocated to tocilizumab compared with etanercept (all P<.001). During follow-up, 83 MACE occurred in the tocilizumab group compared with 78 in the etanercept group. The estimated hazard of MACE for tocilizumab relative to etanercept was 1.05 (95% confidence interval=0.77, 1.43). Result were similar in sensitivity analyses and the on-treatment analysis. Adverse events that occurred more frequently in the tocilizumab group included serious infection and gastrointestinal perforation.

CONCLUSION: 

The trial, which provides insights into the cardiovascular safety of tocilizumab versus etanercept, excluded a relative risk for MACE of 1.43 or higher. This result should be interpreted in the context of the clinical efficacy and the non-cardiovascular safety of tocilizumab.