title: A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy.
abstract: Progressive multifocal leukoencephalopathy (PML) is a rare, complex opportunistic infection of the central nervous system caused by the JC virus. This past decade, PML was increasingly recognized to be associated with the use of immunosuppressive and biologic agents. The risk for PML differs among these agents and remains difficult to quantify because of the complex pathogenesis of PML and the presence of confounding factors. This paper explores and updates the association of PML with different biologic and immunosuppressive agents and proposes an expanded classification system for the risk of PML. We identify three classes of drug that vary by PML risk, latency to infection, and underlying illness. We also review some of the most common agents with known associations to PML and explore risk mitigation strategies that aim to inform the decision-making process for clinicians and patients in the face of the changing incidence of PML and the growing landscape of immunologic agents.
authors.affiliation: Multiple Sclerosis Division of the Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 3W Gates, Philadelphia, PA, USA. salim.chahin@uphs.upenn.edu.
authors.forename: Salim
authors.initials: S
authors.lastname: Chahin
authors.affiliation: Multiple Sclerosis Division of the Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 3W Gates, Philadelphia, PA, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Berger
mesh_terms: D004348:Drug Labeling; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000145:classification*; D007577:JC Virus / Q000276:immunology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000821:virology; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents
keywords: Efalizumab; Mycophenolate mofetil; Natalizumab; Progressive multifocal leukoencephalopathy; Rituximab