Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: a randomized controlled trial

Giles, J. T. et al. (2020) Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: a randomized controlled trial. Arthritis and Rheumatology, 72(1), pp. 31-40. (doi: 10.1002/art.41095) (PMID:31469238)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Giles, J. T., Sattar, N., Gabriel, S., Ridker, P. M., Gay, S., Warne, C., Musselman, D., Brockwell, L., Shittu, E., Klearman, M., and Fleming, T. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Arthritis and Rheumatology
• Publisher: Wiley
• ISSN: 2326-5191
• ISSN (Online): 2326-5205
• Published Online: 27 December 2019
• First Published: First published in Arthritis and Rheumatology 72(1):31-40
• Publisher Policy: Reproduced in accordance with the publisher copyright policy