Efficacy of Rituximab Outlasts B-Cell Repopulation in Multiple Sclerosis: Time to Rethink Dosing?


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
09 2023
Historique:
received: 23 01 2023
accepted: 05 07 2023
medline: 23 8 2023
pubmed: 22 8 2023
entrez: 21 8 2023
Statut: epublish

Résumé

Patients with multiple sclerosis (PwMS) receiving extended dosing of rituximab (RTX) have exhibited no return of disease activity, which suggests that maintenance of deep depletion of circulating B cells is not necessary to maintain the efficacy of RTX in MS. This was a prospective monocentric observational study including all consecutive PwMS who started or continued RTX after 2019, when the medical staff decided to extend the dosing interval up to 24 months for all patients. Circulating B-cell subsets were monitored regularly and systematically in case of relapse. The first extended interval was analyzed. We included 236 PwMS (81% with relapsing-remitting MS; mean [SD] age 43 [12] years; median [range] EDSS score 4 [0-8]; mean relapse rate during the year before RTX start 1.09 [0.99]; 41.5% with MRI activity). The median number of RTX infusions before extension was 4 (1-13). At the time of the analysis, the median delay in dosing was 17 months (8-39); the median proportion of circulating CD19 The efficacy of RTX outlasted substantial reconstitution of circulating B cells in PwMS, which suggests that renewal of the immune system underlies the prolonged effect of RTX in MS. These findings suggest that extended interval dosing of RTX that leads to a significant reconstitution of circulating B cells is safe in PwMS, could reduce the risk of infection, and could improve vaccine efficacy.

Sections du résumé

BACKGROUND AND OBJECTIVES
Patients with multiple sclerosis (PwMS) receiving extended dosing of rituximab (RTX) have exhibited no return of disease activity, which suggests that maintenance of deep depletion of circulating B cells is not necessary to maintain the efficacy of RTX in MS.
METHODS
This was a prospective monocentric observational study including all consecutive PwMS who started or continued RTX after 2019, when the medical staff decided to extend the dosing interval up to 24 months for all patients. Circulating B-cell subsets were monitored regularly and systematically in case of relapse. The first extended interval was analyzed.
RESULTS
We included 236 PwMS (81% with relapsing-remitting MS; mean [SD] age 43 [12] years; median [range] EDSS score 4 [0-8]; mean relapse rate during the year before RTX start 1.09 [0.99]; 41.5% with MRI activity). The median number of RTX infusions before extension was 4 (1-13). At the time of the analysis, the median delay in dosing was 17 months (8-39); the median proportion of circulating CD19
DISCUSSION
The efficacy of RTX outlasted substantial reconstitution of circulating B cells in PwMS, which suggests that renewal of the immune system underlies the prolonged effect of RTX in MS. These findings suggest that extended interval dosing of RTX that leads to a significant reconstitution of circulating B cells is safe in PwMS, could reduce the risk of infection, and could improve vaccine efficacy.

Identifiants

pubmed: 37604695
pii: 10/5/e200152
doi: 10.1212/NXI.0000000000200152
pmc: PMC10442066
pii:
doi:

Substances chimiques

Rituximab 4F4X42SYQ6

Types de publication

Observational Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Roxane Claverie (R)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Marine Perriguey (M)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Audrey Rico (A)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Clemence Boutiere (C)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Sarah Demortiere (S)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Pierre Durozard (P)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Frederic Hilezian (F)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Clea Dubrou (C)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Frederic Vely (F)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Jean Pelletier (J)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

Bertrand Audoin (B)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France. bertrand.audoin@ap-hm.fr.

Adil Maarouf (A)

From the Department of Neurology (B.A., M.P., A.R., C.B., S.D., F.H., J.P., A.M.), CRMBM, University Hospital of Marseille, Aix-Marseille University; Service d'immunologie (D.C., F.V.), Marseille Immunopôle, APHM, Aix Marseille University, CNRS, INSERM, CIML; Faculté de Pharmacie (R.C.), Aix-Marseille University; and Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, France.

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