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No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)

BACKGROUND: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this infl...

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Autores principales: Bonnan, Mickael, Ferrari, Sylvie, Courtade, Henri, Money, Paul, Desblache, Pauline, Barroso, Bruno, Debeugny, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7964121/
https://www.ncbi.nlm.nih.gov/pubmed/33763241
http://dx.doi.org/10.1155/2021/8813498
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author Bonnan, Mickael
Ferrari, Sylvie
Courtade, Henri
Money, Paul
Desblache, Pauline
Barroso, Bruno
Debeugny, Stéphane
author_facet Bonnan, Mickael
Ferrari, Sylvie
Courtade, Henri
Money, Paul
Desblache, Pauline
Barroso, Bruno
Debeugny, Stéphane
author_sort Bonnan, Mickael
collection PubMed
description BACKGROUND: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment. METHODS: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes. RESULTS: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged. CONCLUSION: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.
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spelling pubmed-79641212021-03-23 No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial) Bonnan, Mickael Ferrari, Sylvie Courtade, Henri Money, Paul Desblache, Pauline Barroso, Bruno Debeugny, Stéphane Mult Scler Int Research Article BACKGROUND: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment. METHODS: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes. RESULTS: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged. CONCLUSION: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed. Hindawi 2021-03-08 /pmc/articles/PMC7964121/ /pubmed/33763241 http://dx.doi.org/10.1155/2021/8813498 Text en Copyright © 2021 Mickael Bonnan et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bonnan, Mickael
Ferrari, Sylvie
Courtade, Henri
Money, Paul
Desblache, Pauline
Barroso, Bruno
Debeugny, Stéphane
No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title_full No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title_fullStr No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title_full_unstemmed No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title_short No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial)
title_sort no early effect of intrathecal rituximab in progressive multiple sclerosis (effrite clinical trial)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7964121/
https://www.ncbi.nlm.nih.gov/pubmed/33763241
http://dx.doi.org/10.1155/2021/8813498
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