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Clinical Perspectives on the Molecular and Pharmacological Attributes of Anti-CD20 Therapies for Multiple Sclerosis.

ABSTRACT: Anti-CD20 therapies have demonstrated considerable efficacy in the treatment of relapsing multiple sclerosis, constituting a high-efficacy treatment approach for reducing relapse risk and mitigating disability progression. These therapies have been shown to strongly deplete circulating B cells and small subsets of CD3+ CD4 and CD8 T cells that express low levels of CD20. While the clinical profiles of the various anti-CD20 monoclonal antibodies used in treating multiple sclerosis are well-described in the literature, greater understanding of the implications of their distinct molecular and pharmacological attributes is needed. In this review, we focus on four anti-CD20 monoclonal antibodies-rituximab, ocrelizumab, ofatumumab, and ublituximab-that are currently used, approved, or in late-stage clinical development for the treatment of multiple sclerosis. We provide clinical perspectives on the potential implications of differences in molecular structures, target epitopes, dosing regimens, mechanisms and impact on B-cell depletion and reconstitution, immunogenicity, administration-related reactions, and infection risks.

SUBMITTER: Bar-Or A

PROVIDER: S-EPMC8351586 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAnti-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.ObjectiveTo investigate the duration of the anti-CD20 treatment-induced effects on humoral responses to COVID-19 vaccines.MethodsThis 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).ResultsA 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.ConclusionAnti-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.

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Clinical Perspectives on the Molecular and Pharmacological Attributes of Anti-CD20 Therapies for Multiple Sclerosis.

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