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CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis

BACKGROUND: Ocrelizumab maintains B-cell depletion via six-monthly dosing. Whilst this controls relapsing multiple sclerosis, it also inhibits seroconversion following SARS-CoV-2 vaccination unlike that seen following alemtuzumab and cladribine treatment. Emerging reports suggest that 1–3% B-cell re...

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Autores principales: Baker, David, MacDougall, Amy, Kang, Angray S., Schmierer, Klaus, Giovannoni, Gavin, Dobson, Ruth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642825/
https://www.ncbi.nlm.nih.gov/pubmed/34902760
http://dx.doi.org/10.1016/j.msard.2021.103448
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author Baker, David
MacDougall, Amy
Kang, Angray S.
Schmierer, Klaus
Giovannoni, Gavin
Dobson, Ruth
author_facet Baker, David
MacDougall, Amy
Kang, Angray S.
Schmierer, Klaus
Giovannoni, Gavin
Dobson, Ruth
author_sort Baker, David
collection PubMed
description BACKGROUND: Ocrelizumab maintains B-cell depletion via six-monthly dosing. Whilst this controls relapsing multiple sclerosis, it also inhibits seroconversion following SARS-CoV-2 vaccination unlike that seen following alemtuzumab and cladribine treatment. Emerging reports suggest that 1–3% B-cell repopulation facilitates seroconversion after CD20-depletion. OBJECTIVE: To determine the frequency of B-cell repopulation levels during and after ocrelizumab treatment. METHODS: Relapse data, lymphocyte and CD19 B-cell numbers were obtained following requests to clinical trial data-repositories. Information was extracted from the phase II ocrelizumab extension (NCT00676715) trial and the phase III cladribine tablet (NCT00213135) and alemtuzumab (NCT00530348/NCT00548405) trials obtained clinical trial data requests RESULTS: Only 3–5% of people with MS exhibit 1% B-cells at 6 months after the last infusion following 3–4 cycles of ocrelizumab, compared to 50–55% at 9 months, and 85–90% at 12 months. During this time relapses occurred at consistent disease-breakthrough rates compared to people during standard therapy. In contrast most people (90–100%) exhibited more than 1% B-cells during treatment with either cladribine or alemtuzumab. CONCLUSIONS: Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. However, few people repopulate peripheral B-cells with standard ocrelizumab dosing. Controlled studies are warranted to examine a view that delaying the dosing interval by 3–6 months may allow more people to potentially seroconvert after vaccination.
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spelling pubmed-86428252021-12-06 CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis Baker, David MacDougall, Amy Kang, Angray S. Schmierer, Klaus Giovannoni, Gavin Dobson, Ruth Mult Scler Relat Disord Original Article BACKGROUND: Ocrelizumab maintains B-cell depletion via six-monthly dosing. Whilst this controls relapsing multiple sclerosis, it also inhibits seroconversion following SARS-CoV-2 vaccination unlike that seen following alemtuzumab and cladribine treatment. Emerging reports suggest that 1–3% B-cell repopulation facilitates seroconversion after CD20-depletion. OBJECTIVE: To determine the frequency of B-cell repopulation levels during and after ocrelizumab treatment. METHODS: Relapse data, lymphocyte and CD19 B-cell numbers were obtained following requests to clinical trial data-repositories. Information was extracted from the phase II ocrelizumab extension (NCT00676715) trial and the phase III cladribine tablet (NCT00213135) and alemtuzumab (NCT00530348/NCT00548405) trials obtained clinical trial data requests RESULTS: Only 3–5% of people with MS exhibit 1% B-cells at 6 months after the last infusion following 3–4 cycles of ocrelizumab, compared to 50–55% at 9 months, and 85–90% at 12 months. During this time relapses occurred at consistent disease-breakthrough rates compared to people during standard therapy. In contrast most people (90–100%) exhibited more than 1% B-cells during treatment with either cladribine or alemtuzumab. CONCLUSIONS: Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. However, few people repopulate peripheral B-cells with standard ocrelizumab dosing. Controlled studies are warranted to examine a view that delaying the dosing interval by 3–6 months may allow more people to potentially seroconvert after vaccination. Elsevier B.V. 2022-01 2021-12-04 /pmc/articles/PMC8642825/ /pubmed/34902760 http://dx.doi.org/10.1016/j.msard.2021.103448 Text en © 2021 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Original Article
Baker, David
MacDougall, Amy
Kang, Angray S.
Schmierer, Klaus
Giovannoni, Gavin
Dobson, Ruth
CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title_full CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title_fullStr CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title_full_unstemmed CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title_short CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
title_sort cd19 b cell repopulation after ocrelizumab, alemtuzumab and cladribine: implications for sars-cov-2 vaccinations in multiple sclerosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642825/
https://www.ncbi.nlm.nih.gov/pubmed/34902760
http://dx.doi.org/10.1016/j.msard.2021.103448
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