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

•Clinical trial data was interrogated to determine the frequency of 1–3% B cell repopulation over 12–18 months.•Few people repopulate after standard 6 monthly ocrelizumab dosing, but an extended dosing interval could allow many more people to repopulate B cells.•CD19+ B cells rapidly repopulated after cladribine and alemtuzumab treatment. 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. To determine the frequency of B-cell repopulation levels during and after ocrelizumab treatment. 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 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. 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.