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

Tobias Moser; Ciara O'Sullivan; Ferdinand Otto; Wolfgang Hitzl; Georg Pilz; Kerstin Schwenker; Cornelia Mrazek; Elisabeth Haschke-Becher; Eugen Trinka; Peter Wipfler; Andrea Harrer

doi:10.1177/17562864221092092

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

Ther Adv Neurol Disord. 2022 Apr 22:15:17562864221092092. doi: 10.1177/17562864221092092. eCollection 2022.

Authors

Tobias Moser¹, Ciara O'Sullivan², Ferdinand Otto², Wolfgang Hitzl^{3

4

5}, Georg Pilz², Kerstin Schwenker², Cornelia Mrazek⁶, Elisabeth Haschke-Becher⁶, Eugen Trinka^{2

7}, Peter Wipfler², Andrea Harrer^{2

8}

Affiliations

¹ Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Ignaz-Harrer-Straße 79, 5020 Salzburg, Austria.
² Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg, Austria.
³ Research Management (RM): Biostatistics and Publication of Clinical Studies Team, Paracelsus Medical University, Salzburg, Austria.
⁴ Department of Ophthalmology and Optometry, Paracelsus Medical University, Salzburg, Austria.
⁵ Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University, Salzburg, Austria.
⁶ Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
⁷ Neuroscience Institute, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, Salzburg, Austria.
⁸ Department of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria.

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 < 0.00001). Significantly increased antibody levels compared with the control cohort were found among pwMS who were vaccinated >18 months after treatment discontinuation (19-24 months: n = 2, p = 0.013; 25-36 months: n = 9; p < 0.001). The interindividual kinetics for B-cell reconstitution were heterogeneous and mean B-cell counts approached normal ranges 18 months after treatment discontinuation. There was no correlation of B-cell repopulation and vaccine responses. Mean total IgG, IgM, and IgA levels remained within the reference range.

Conclusion: Anti-CD20-induced inhibition of humoral responses to COVID-19 vaccines is transient and antibody production was more pronounced >18 months after anti-CD20 treatment discontinuation. The immunological effect on B-cell counts appears to wane by the same time.

Keywords: B-cell depletion; B-cell therapy; SARS-CoV-2; antibody titers; immune reconstitution; immunoglobulins; long-term effects.