Risk of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patient Treated With Natalizumab: A Systematic Review

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.

Use of natalizumab in persons with multiple sclerosis: 2022 update

“…The long-term studies (Boziki et al, 2021;Butzkueven et al, 2020a;Guger et al, 2021;Prosperini et al, 2017) confirm that natalizumab is a highly effective treatment option for PwMS. Risk stratification for PML and risk management strategies that include patient education and close monitoring have improved outcomes and reduced the number of natalizumab-associated PML incidences (Vivekanandan et al, 2021;Vukusic et al, 2020). With close monitoring, PwMS at high risk for PML may be kept on natalizumab treatment instead of discontinuing.…”

“…2 is an algorithm for MRI-based PML safety monitoring during natalizumab therapy. As a result of patient education and monitoring strategies, the incidence of natalizumab-associated PML has decreased in recent years (Vivekanandan et al, 2021;Vukusic et al, 2020).…”

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy

“…Indeed, apart from low CD4 þ cell count, the impact of immunosuppressive factors on JCV regulation and reactivation is not well known [32,36]. For example, the occurrence of PML in patients treated with ruxolitinib, a selective Janus kinase inhibitor, despite normal CD4 þ T-cell count, or in patients treated with natalizumab, a humanized IgG4 antibody that does not affect CD4 þ T-cell count, suggests the involvement of other immunological factors [37,38]. Other limitations include the retrospective nature of the study and the small number of cases identified.…”