title: Sorting out the risks in progressive multifocal leukoencephalopathy.
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.
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A50, Cleveland, OH 44195, USA.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Calabrese
authors.affiliation: St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: Eamonn
authors.initials: E
authors.lastname: Molloy
authors.affiliation: Department of Neurology, Perelman School of Medicine, 3400 Spruce Street, 3W Gates, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Berger
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D002464:Cell Migration Inhibition; D015986:Confounding Factors, Epidemiologic; D003657:Decision Making; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000145:classification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000453:epidemiology*; D000069442:Natalizumab; D018570:Risk Assessment
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; C472181:efalizumab