Drug Safety

, Volume 33, Issue 11, pp 969–983 | Cite as

Progressive Multif ocal Leukoencephalopathy and Newer Biological Agents

Review Article

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the brain due to a polyoma virus, JC virus. Despite the ubiquity of this virus, PML is rare and almost always seen in association with an underlying immunosuppressive condition. In the last 30 years, AIDS has been the most common predisposing factor. The observation of PML attending the use of certain monoclonal antibody therapies and other pharmacological agents has raised concerns about the safety profile of these agents, but has also provided a window into the pathogenesis of PML. Certain agents, such as the monoclonal antibodies natalizumab, an α4b1 and α4β7 integrin inhibitor, and efalizumab, an antibody directed against CD11a, appear to uniquely predispose to PML. Prior to their introduction for multiple sclerosis and Crohn’s disease with respect to natalizumab, and psoriasis with respect to efalizumab, PML had never been observed with these disorders. PML occurring with other agents that currently carry US FDA-mandated ‘black-box’ warnings, such as rituximab, an antibody directed to CD20, or mycophenolate mofetil, a drug that inhibits T- and B-cell proliferation, typically occur in the background of underlying disorders that have already been identified as risks for PML. This review will focus on the available data regarding the risk for PML with monoclonal antibodies and other drugs. A biologically plausible explanation for the increased risk of PML will be proposed, as well as potential strategies for mitigating disease risk.

Notes

Acknowledgements

Dr Berger has received research funding from Bayer, EMD-Serono and Biogen, and speakers honoraria from Bayer, EMD Serono and Teva. He has served as a consultant to Asphelia, Astellas, Bayer, Biogen, Genentech, GlaxoSmithKline, Millenium and Pfizer. No funding was provided for the preparation of this review.

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© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Department of Neurologyiversity of Kentucky College of MedicineLexingtonUSA

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