title: Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy.
abstract: Natalizumab, a highly effective therapy for relapsing-remitting multiple sclerosis, is associated with a risk of progressive multifocal leukoencephalopathy (PML). The objective of this analysis was to examine factors predicting survival in a large natalizumab-associated PML global population. Patients with natalizumab-associated PML identified through postmarketing surveillance were followed up for up to 24 months using a structured questionnaire completed by treating physicians. Demographic and clinical characteristics, JC viral load, magnetic resonance imaging (MRI) results, and Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores were compared in survivors and nonsurvivors. Kaplan-Meier analysis was used to model survival function. Among the 336 patients included in this analysis, 76 % survived, with mean follow-up time from PML diagnosis of 16.1 months for survivors; mean time from diagnosis to death was 4.7 months for nonsurvivors. Survivors were significantly younger at diagnosis, had significantly lower EDSS scores and higher KPS scores prior to PML diagnosis, and had significantly lower cerebrospinal fluid JC viral load at the time of diagnosis. Patients with less extensive disease on MRI at diagnosis had a higher survival rate than those with widespread disease. Survivors generally had less functional disability pre-PML, at PML diagnosis, and in subsequent months. In survivors, functional disability appeared to stabilize approximately 6 months post-PML diagnosis. In this analysis, younger age at diagnosis, less functional disability prior to PML diagnosis, lower JC viral load at diagnosis, and more localized brain involvement by MRI at the time of diagnosis appeared to predict improved survival in natalizumab-associated PML.
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Tuan
authors.initials: T
authors.lastname: Dong-Si
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA. sarah.gheuens@biogenidec.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gheuens
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Gangadharan
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Made
authors.initials: M
authors.lastname: Wenten
authors.affiliation: Data Sciences, Biogen Idec Inc., Cambridge, MA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Philip
authors.affiliation: Data Sciences, Biogen Idec Inc., Cambridge, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: McIninch
authors.affiliation: Data Sciences, Biogen Idec Inc., Cambridge, MA, USA.
authors.forename: Shoibal
authors.initials: S
authors.lastname: Datta
authors.affiliation: Neurology Research and Development, Biogen Idec Inc., Cambridge, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Richert
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Bozic
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Bloomgren
authors.affiliation: Drug Safety and Risk Management, Biogen Idec Inc., 225 Binney Street, Cambridge, MA, 02142, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Richman
authors.affiliation: Marienkrankenhaus, Academic Teaching Hospital, University of Hamburg, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007577:JC Virus; D053208:Kaplan-Meier Estimate; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000401:mortality* / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab / Q000009:adverse effects*; D017741:Survivors / Q000706:statistics & numerical data; D019562:Viral Load; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Expanded Disability Status Scale; Karnofsky Performance Scale; Natalizumab; Progressive multifocal leukoencephalopathy; Survival