Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study

Abstract

Background: Anti-CD20 therapies induce pronounced B-cell depletion and blunt humoral responses to vaccines. Recovery kinetics of anti-CD20 therapy-mediated cellular and humoral effects in people with multiple sclerosis (pwMS) are poorly defined. Objective: To investigate the duration of the anti-CD20 treatment-induced effects on humoral responses to COVID-19 vaccines. Methods: This retrospective observational study included pwMS who had discontinued anti-CD20 therapy for ⩾12 months and remained without immunomodulation. We retrieved demographics and laboratory parameters including B-cell counts and immunoglobulin (IgG, IgM, IgA) levels prior to anti-CD20 commencement (baseline) and longitudinally after anti-CD20 treatment discontinuation from electronic medical records. Humoral responses to SARS-CoV-2 vaccines were compared with a population of 11 pwMS with ongoing anti-CD20 medication (control cohort). Results: A total of 24 pwMS had discontinued anti-CD20 therapy for a median of 34 months (range: 16–38 months). Antibody responses to COVID-19 vaccines were available in 17 (71%). Most individuals ( n = 15, 88%) elicited a measurable antibody response [mean: 774 BAU/ml (±SD 1283 BAU/ml)] to SARS-CoV-2 immunization on average 22 months (range: 10–30 months) from the last anti-CD20 infusion, which was higher compared with the population with ongoing anti-CD20 therapy ( n = 11, mean: 12.36 ± SD 11.94 BAU/ml; p 18 months after treatment discontinuation (19–24 months: n = 2, p = 0.013; 25–36 months: n = 9; p 18 months after anti-CD20 treatment discontinuation. The immunological effect on B-cell counts appears to wane by the same time.