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Baker D, MacDougall A, Kang AS, et al. CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis. Mult Scler Relat Disord. 2021;57:103448doi: 10.1016/j.msard.2021.103448.
Baker, D., MacDougall, A., Kang, A. S., Schmierer, K., Giovannoni, G., & Dobson, R. (2021). CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis. Multiple sclerosis and related disorders, 57103448. https://doi.org/10.1016/j.msard.2021.103448
Baker, David, et al. "CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis." Multiple sclerosis and related disorders vol. 57 (2021): 103448. doi: https://doi.org/10.1016/j.msard.2021.103448
Baker D, MacDougall A, Kang AS, Schmierer K, Giovannoni G, Dobson R. CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis. Mult Scler Relat Disord. 2021 Dec 04;57:103448. doi: 10.1016/j.msard.2021.103448. Epub 2021 Dec 04. PMID: 34902760.
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Mult Scler Relat Disord. 2021 Dec 04;57:103448. doi: 10.1016/j.msard.2021.103448. Epub 2021 Dec 04.

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

Multiple sclerosis and related disorders

David Baker, Amy MacDougall, Angray S Kang, Klaus Schmierer, Gavin Giovannoni, Ruth Dobson

Affiliations

  1. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom. Electronic address: [email protected].
  2. Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  3. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Centre for Oral Immunobiology and Regenerative Medicine, Dental Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  4. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.
  5. Preventive Neurology Unit, Wolfson Institute of Population Medicine, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. Electronic address: [email protected].

PMID: 34902760 DOI: 10.1016/j.msard.2021.103448

Abstract

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.

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Alemtuzumab; CD20; Cladribine; Multiple sclerosis; Ocrelizumab; Rituximab

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