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Sorting out the risks in progressive multifocal leukoencephalopathy

Nature Reviews Rheumatology volume 11, pages 119–123 (2015)Cite this article

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Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic infection of the central nervous system, caused by reactivation of the ubiquitous JC virus. PML is a devastating disease that is frequently fatal, and although survival rates have improved, patients who survive PML often experience considerable neurological deficits. PML was associated with a variety of immunosuppressive therapies in the past decade, but attribution of causality is difficult owing to the presence of confounding factors and to an inadequate understanding of the underlying pathogenesis of this disease. This uncertainty has hindered efforts for shared decision-making between physicians and their patients and, in some cases, discouraged the use of potentially beneficial therapies. We propose a categorization of immunosuppressive agents according to their risk of PML to support a better-informed decision-making process when evaluating the risks and benefits of these therapies.

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Figure 1: Infection with JC virus is at first asymptomatic and presumably occurs at an early age by oral route.

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Authors and Affiliations

  1. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A50, Cleveland, 44195, OH, USA

    Leonard H. Calabrese

  2. St Vincent's University Hospital, Elm Park, 4, Dublin, Ireland

    Eamonn Molloy

  3. Department of Neurology, Perelman School of Medicine, 3400 Spruce Street, 3W Gates, University of Pennsylvania, Philadelphia, 19104, PA, USA

    Joseph Berger

Authors
  1. Leonard H. Calabrese
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  2. Eamonn Molloy
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  3. Joseph Berger
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Contributions

All authors contributed equally to researching data for the article, discussions of the content, writing the article and editing the manuscript before submission.

Corresponding author

Correspondence to Leonard H. Calabrese.

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Competing interests

L.H.C. has served as consultant to Genentech, GlaxoSmithKline and Pfizer in the area of progressive multifocal leukoencephalopathy (PML). E.M. has obtained research support from Roche, has served on advisory boards for Bristol-Myers Squibb, Pfizer and MSD, and received payment for developing educational materials relating to PML from GlaxoSmithKline. J.B. serves on the PML Adjudication Committees of Amgen, Astra Zeneca, Bristol-Myers Squibb, Eisai, Janssen, Millennium, Parexel, Pfizer, Roche and Takeda; he is a consultant to Genentech, Genzyme, Incyte, Inhibikase Therapeutics, Johnson & Johnson and Novartis. He has received grants from the PML Consortium, Biogen Idec and Novartis.

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Calabrese, L., Molloy, E. & Berger, J. Sorting out the risks in progressive multifocal leukoencephalopathy. Nat Rev Rheumatol 11, 119–123 (2015). https://doi.org/10.1038/nrrheum.2014.167

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