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Predictors of survival and functional outcomes in natalizumab-associated
progressive multifocal leukoencephalopathy
#MMPMID25771865
Dong-Si T
; Gheuens S
; Gangadharan A
; Wenten M
; Philip J
; McIninch J
; Datta S
; Richert N
; Bozic C
; Bloomgren G
; Richman S
; Weber T
; Clifford DB
J Neurovirol
2015[Dec]; 21
(6
): 637-44
PMID25771865
show ga
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.
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