Clinical outcomes of COVID-19 in patients with multiple sclerosis treated with ocrelizumab in the pre- and post-SARS-CoV-2 vaccination periods: Insights from Israel

Weberpals, Janick; Roumpanis, Spyros; Barer, Yael; Ehrlich, Sharon; Jessop, Nikki; Pedotti, Rosetta; Vaknin‐Dembinsky, Adi; Brill, Livnat; Chodick, Gabriel; Rouzic, Erwan Muros‐Le

doi:10.1016/j.msard.2022.104153

Cited by 6 publications

(7 citation statements)

References 16 publications

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“…However, results from the Italian CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study indicated a significant reduction (70%) in the rate of hospitalization after SARS-CoV-2 vaccination, including in patients treated with ocrelizumab (134). This correlated with a small cohort showing that SARS-CoV-2 infections were more severe in non-vaccinated (33.3%) vs. vaccinated patients (25%) (135).…”

Section: A Focus On Sars-cov-2 Vaccinationmentioning

confidence: 98%

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Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic

et al. 2023

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The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.

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Section: A Focus On Sars-cov-2 Vaccinationmentioning

confidence: 98%

“…This correlated with a small cohort showing that SARS-CoV-2 infections were more severe in non-vaccinated (33.3%) vs . vaccinated patients (25%) ( 135 ).…”

Section: Safety Of Anti-cd20 Mabsmentioning

confidence: 99%

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic

et al. 2023

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“…At the same time, B-cell-depleted patients do benefit from vaccinations, as evidenced by their many-fold lower COVID-19 hospitalization rates following vaccination relative to the pre-vaccination epoch. 10,11 To better understand the magnitude and durability of COVID-19 vaccine-induced immunity in patients treated with ocrelizumab, a B-cell depleting monoclonal therapy, we designed a prospective study-VIOLA ('Vaccine-generated Immunity in Ocrelizumab-treated Patients: Longitudinal Assessments', NCT04843774). The study assessed humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA vaccine series and to the third (booster) dose at multiple prespecified time points up to 2 years from the initial vaccination.…”

Section: 2mentioning

confidence: 99%

“…9 At the same time, B-cell-depleted patients do benefit from vaccinations, as evidenced by their many-fold lower COVID-19 hospitalization rates following vaccination relative to the pre-vaccination epoch. 10,11…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

Kister,

Curtin,

Piquet

et al. 2024

Preprint

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Objectives: 1. To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; 2. to identify predictors of immune responses to vaccination; and 3. to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. Methods: 60 Ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys©, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementary determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results: The primary vaccination induced an 11-208-fold increase in binding and neutralizing antibody levels and a 3-4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3-5-fold increase in binding antibodies and 4-5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation: Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.

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“… 9 At the same time, B‐cell‐depleted patients do benefit from vaccinations, as evidenced by their many‐fold lower COVID‐19 hospitalization rates following vaccination relative to the pre‐vaccination epoch. 10 , 11 The benefit of vaccinations in B‐cell‐depleted patients may be in large part due to the intactness of T‐cell responses, which play a critical role in containing SARS‐CoV‐2 infection. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of immunity toSARS‐CoV2in ocrelizumab‐treatedMSpatients up to 2 years afterCOVID‐19 vaccination

Kister,

Curtin,

Piquet

et al. 2024

Ann Clin Transl Neurol

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Objectives(1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity.MethodsSixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses.ResultsThe primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity.InterpretationHumoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

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Clinical outcomes of COVID-19 in patients with multiple sclerosis treated with ocrelizumab in the pre- and post-SARS-CoV-2 vaccination periods: Insights from Israel

Cited by 6 publications

References 16 publications

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

Longitudinal study of immunity toSARS‐CoV2in ocrelizumab‐treatedMSpatients up to 2 years afterCOVID‐19 vaccination

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