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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13365-015-0316-4) contains supplementary material, which is available to authorized users.
Highlights
Multiple sclerosis (MS) is an immune-mediated disease resulting in progressive neurological disability
Natalizumab is associated with progressive multifocal leukoencephalopathy (PML), an opportunistic demyelinating disease of the brain caused by the JC virus (JCV) (Langer-Gould et al 2005)
In contrast to natalizumab-associated PML, HIV+ PML appears to show a longer survival with increasing age (Casado et al 2013), while age does not seem to influence survival in transplant recipients with PML (Mateen et al 2011)
Summary
Multiple sclerosis (MS) is an immune-mediated disease resulting in progressive neurological disability. Natalizumab is associated with progressive multifocal leukoencephalopathy (PML), an opportunistic demyelinating disease of the brain caused by the JC virus (JCV) (Langer-Gould et al 2005). In patients who test positive for anti-JCV antibodies, the risk of natalizumab-associated PML increases with treatment duration (especially >2 years of therapy) and prior use of immunosuppressant therapy (Bloomgren et al 2012). Survival in patients with acquired immune deficiency syndrome (AIDS)-associated PML has been linked to specific patient characteristics, JC viral load in cerebrospinal fluid (CSF) (Yiannoutsos et al 1999), and underlying immunologic function, such as low CD4+ cell count at disease onset (Gasnault et al 2011)
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