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Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience

The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody...

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Autores principales: Perncezky, Julian, Sellner, Johann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580073/
https://www.ncbi.nlm.nih.gov/pubmed/36277271
http://dx.doi.org/10.1177/11795735221135485
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author Perncezky, Julian
Sellner, Johann
author_facet Perncezky, Julian
Sellner, Johann
author_sort Perncezky, Julian
collection PubMed
description The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody blocks the α4β1 integrin-mediated leukocyte-endothelial interaction and thereby inhibits the migration of immune cells to the brain parenchyma. However, treatment with natalizumab carries the risk of progressive multifocal leukoencephalopathy (PML). This potentially lethal side effect is a significant limitation for treatment initiation and long-term therapy. Natalizumab is given intravenously or subcutaneously in the standard dose of 300 mg every 4 weeks, allowing drug concentrations at levels that ensure continuous α4β1 integrin receptor saturation on the surface of immune cells. Extended-interval dosing (EID) is an emerging treatment approach that aims to mitigate the natalizumab-related PML risk by prolonging the standard infusion intervals to 6 weeks or even more. This treatment approach may abrogate the PML risk due to improved immune surveillance within the central nervous system while maintaining clinical efficacy. Moreover, even an individual interval dosing can be envisioned based on the availability of a biomarker that is capable of monitoring both safety and efficacy aspects. This review summarizes the early and encouraging evidence for EID from observational and randomized-controlled trials and discusses current limitations and upcoming challenges for introducing a tailored treatment approach.
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spelling pubmed-95800732022-10-20 Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience Perncezky, Julian Sellner, Johann J Cent Nerv Syst Dis Review The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody blocks the α4β1 integrin-mediated leukocyte-endothelial interaction and thereby inhibits the migration of immune cells to the brain parenchyma. However, treatment with natalizumab carries the risk of progressive multifocal leukoencephalopathy (PML). This potentially lethal side effect is a significant limitation for treatment initiation and long-term therapy. Natalizumab is given intravenously or subcutaneously in the standard dose of 300 mg every 4 weeks, allowing drug concentrations at levels that ensure continuous α4β1 integrin receptor saturation on the surface of immune cells. Extended-interval dosing (EID) is an emerging treatment approach that aims to mitigate the natalizumab-related PML risk by prolonging the standard infusion intervals to 6 weeks or even more. This treatment approach may abrogate the PML risk due to improved immune surveillance within the central nervous system while maintaining clinical efficacy. Moreover, even an individual interval dosing can be envisioned based on the availability of a biomarker that is capable of monitoring both safety and efficacy aspects. This review summarizes the early and encouraging evidence for EID from observational and randomized-controlled trials and discusses current limitations and upcoming challenges for introducing a tailored treatment approach. SAGE Publications 2022-10-17 /pmc/articles/PMC9580073/ /pubmed/36277271 http://dx.doi.org/10.1177/11795735221135485 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Perncezky, Julian
Sellner, Johann
Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title_full Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title_fullStr Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title_full_unstemmed Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title_short Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
title_sort natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580073/
https://www.ncbi.nlm.nih.gov/pubmed/36277271
http://dx.doi.org/10.1177/11795735221135485
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