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Cardiovascular safety of biologic therapies for the treatment of RA

Nature Reviews Rheumatology volume 8, pages 13–21 (2012)Cite this article

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Abstract

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence—mainly derived from observational databases and registries—suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Key Points

  • Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA)

  • Evidence derived from observational studies suggests that cardiovascular risk in people with RA might be reduced with the use of methotrexate or anti-TNF biologic agents, or both

  • In the absence of large randomized trials adequately powered to test cardiovascular outcomes, definitive conclusions about the cardiovascular risks and/or cardioprotective effects of biologic agents cannot yet be made

  • Despite inherent limitations of observational research, large registries of patients receiving long-term RA therapy represent a promising approach to studying the cardiovascular safety of emerging RA therapeutics

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Figure 1: Forest plot of the adjusted relative risk of cardiovascular events in patients with RA treated with anti-TNF agents versus nonbiologic DMARDs in published observational cohorts.

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Acknowledgements

Dr Greenberg received partial support for this work from the NIH (K23AR054412) and the Arthritis National Research Foundation. Dr Furer received partial support from the Arthritis Foundation.

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Authors and Affiliations

  1. Department of Rheumatology, New York University (NYU) Hospital for Joint Diseases, 301 East 17th Street, Suite 1410, New York, 10003, NY, USA

    Jeffrey D. Greenberg & Victoria Furer

  2. Mount Sinai Cardiovascular Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1074, New York, 10029, NY, USA

    Michael E. Farkouh

Authors
  1. Jeffrey D. Greenberg
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  2. Victoria Furer
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Contributions

All authors made a substantial contribution to discussion of content and to review/editing of the manuscript before submission. J. D. Greenberg and V. Furer contributed equally to researching data for the article and to writing the article.

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Correspondence to Jeffrey D. Greenberg.

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Competing interests

J. D. Greenberg declares that he is a consultant for AstraZeneca, CORRONA, Novartis and Pfizer, and is a stock holder or director of CORRONA. M. Farkouh declares that he is a consultant for Genentech. V. Furer declares no competing interests.

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Greenberg, J., Furer, V. & Farkouh, M. Cardiovascular safety of biologic therapies for the treatment of RA. Nat Rev Rheumatol 8, 13–21 (2012). https://doi.org/10.1038/nrrheum.2011.168

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