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.
Keywords: Alemtuzumab; CD20; Cladribine; Multiple sclerosis; Ocrelizumab; Rituximab.
【저자키워드】 multiple sclerosis, rituximab, Ocrelizumab, CD20, Cladribine, Alemtuzumab, 【초록키워드】 Treatment, vaccination, clinical trial, Trial, rituximab, B cell, lymphocyte, Seroconversion, Control, SARS-CoV-2 vaccination, B-cell, Frequency, Standard therapy, Relapse, CD19, Tablet, extension, seroconvert, Multiple, dosing interval, MOST, occurred, inhibit, facilitate, exhibited, determine, maintain, Controlled, relapsing, 【제목키워드】 B cell, SARS-CoV-2 vaccination, CD19,