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

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.

• Authors: David Baker, Amy MacDougall, Angray S Kang, Klaus Schmierer, Gavin Giovannoni, Ruth Dobson
• Journal: Multiple sclerosis and related disorders (Mult Scler Relat Disord) Vol. 57 Pg. 103448 (Jan 2022) ISSN: 2211-0356 [Electronic] Netherlands
• PMID: 34902760 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• COVID-19 Vaccines
• Alemtuzumab
• Cladribine
• ocrelizumab

Topics

• Alemtuzumab (therapeutic use)
• Antibodies, Monoclonal, Humanized
• COVID-19
• COVID-19 Vaccines
• Cladribine
• Humans
• Multiple Sclerosis (drug therapy)
• Multiple Sclerosis, Relapsing-Remitting (drug therapy)
• SARS-CoV-2
• Vaccination