Abstract
Natalizumab, a monoclonal antibody acting on alpha4 integrin receptors, is frequently used to treat multiple sclerosis patients. The biggest downside is the risk of development of progressive multifocal leukoencephalopathy, an immune-related condition affecting mainly the central nervous system. The presence of the John Cunningham virus (JCV) and its reactivation is an important factor in the development of progressive multifocal leukoencephalopathy (PML). This study highlights its different proposed mechanism and risk factors strongly related to natalizumab-induced progressive multifocal leukoencephalopathy. The pieces of literature will also be reviewed to look for a relation between the JCV and natalizumab-induced progressive multifocal leukoencephalopathy in multiple sclerosis treated patients.The articles were searched from three databases and reviewed systematically. The inclusion criteria for this study were patients aged 20-50 years, English language paper, full-text availability, and human studies, whereas articles on patients with AIDS and cancer-related disease prior to natalizumab treatment were excluded.Out of 6531 articles identified after applying the search strategy on three main databases PubMed, Google Scholar, and ResearchGate, a total of 32 articles were finalized for the review. This study follows the guidelines listed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist 2009. The data collected from these finalized articles were pertaining to the risk factor related to natalizumab induced progressive multifocal leukoencephalopathy and the mechanism related to its pathogenesis. Natalizumab is known to have the potential to cause progressive multifocal leukoencephalopathy in treated patients; here, we evaluate a close relationship of its related risk factors. The articles studied exhibit a close relationship between the length of natalizumab treatment and the presence of the JCV before infusion of natalizumab. From our analysis, it seems that the mechanism related to natalizumab-induced PML is strongly related to antigen-specific T cells and its effects. The frequency of monitoring and vigilance on the management of patients treated with natalizumab will help detect progressive multifocal leukoencephalopathy.
Highlights
BackgroundThe global incidence of progressive multifocal leukoencephalopathy (PML) in natalizumab treated patients is 4.08/1000 patients (95% confidence interval (CI) 3.80-4.36/1000 patients, and the survival rate is approximately 70-75% [1,2]
Natalizumab is known to have the potential to cause progressive multifocal leukoencephalopathy in treated patients; here, we evaluate a close relationship of its related risk factors
Progressive multifocal leukoencephalopathy, a fatal disease, is a risk in multiple sclerosis patients being treated with natalizumab or other monoclonal antibodies
Summary
BackgroundThe global incidence of progressive multifocal leukoencephalopathy (PML) in natalizumab treated patients is 4.08/1000 patients (95% confidence interval (CI) 3.80-4.36/1000 patients, and the survival rate is approximately 70-75% [1,2]. In November 2004, the approval of natalizumab in managing multiple sclerosis (MS) by the FDA was accelerated based on one-year results from two randomized, placebo-controlled phase three clinical trials, the affirm and sentinel trials [2]. The drug was removed from the market in February 2005, and the active ongoing trials were terminated due to the two reported cases of PML in the sentinel trial [3]. Natalizumab was reintroduced into the market in June 2006 with FDA approval as a monotherapy in relapsing-remitting multiple sclerosis. PML is a diffuse demyelinating disease of the white matter of the brain due to the John Cunningham virus (JCV) and its infection on oligodendrocytes creating a widespread lesion in the brain [3]. PML diagnosis is by the neuropathological demonstration of the histopathological triad
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