Impact of extended interval dosing of ocrelizumab on immunoglobulin levels in multiple sclerosis.
B cell depletion
Translation to patients
anti-CD20 therapy
extended interval dosing
hypogammaglobulinemia
multiple sclerosis
ocrelizumab
personalized dosing
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
09 Jun 2023
09 Jun 2023
Historique:
received:
17
01
2023
revised:
17
04
2023
accepted:
02
05
2023
medline:
12
6
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
ppublish
Résumé
Long-term B cell depletion with ocrelizumab in multiple sclerosis (MS) is associated with severe side effects such as hypogammaglobulinemia and infections. Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing (EID) scheme. Immunoglobulin levels of 51 patients with ≥24 months of treatment with ocrelizumab were analyzed. After ≥4 treatment cycles, patients chose to either continue on the standard interval dosing (SID) regimen (n = 14) or, in the case of clinically and radiologically stable disease, switch to B cell-adapted EID (n = 12, next dose at CD19 Levels of immunoglobulin M (IgM) declined rapidly under ocrelizumab treatment. Risk factors for IgM and IgA hypogammaglobulinemia were lower levels at baseline and more previous disease-modifying therapies. B cell-adapted EID of ocrelizumab increased the mean time until next infusion from 27.3 to 46.1 weeks. Ig levels declined significantly in the SID group over 12 months but not in the EID group. Previously stable patients remained stable under EID as measured by expanded disability status scale (EDSS), neurofilament light chain, timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT), symbol digit modalities test (SDMT), and multiple sclerosis impact scale (MSIS-29). In our pilot study, B cell-adapted EID of ocrelizumab prevented the decline of Ig levels without affecting disease activity in previously stable patients with MS. Based on these findings, we propose a new algorithm for long-term ocrelizumab treatment. This study was supported by the Deutsche Forschungsgemeinschaft (SFB CRC-TR-128, SFB 1080, and SFB CRC-1292) and the Hertie Foundation.
Sections du résumé
BACKGROUND
BACKGROUND
Long-term B cell depletion with ocrelizumab in multiple sclerosis (MS) is associated with severe side effects such as hypogammaglobulinemia and infections. Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing (EID) scheme.
METHODS
METHODS
Immunoglobulin levels of 51 patients with ≥24 months of treatment with ocrelizumab were analyzed. After ≥4 treatment cycles, patients chose to either continue on the standard interval dosing (SID) regimen (n = 14) or, in the case of clinically and radiologically stable disease, switch to B cell-adapted EID (n = 12, next dose at CD19
FINDINGS
RESULTS
Levels of immunoglobulin M (IgM) declined rapidly under ocrelizumab treatment. Risk factors for IgM and IgA hypogammaglobulinemia were lower levels at baseline and more previous disease-modifying therapies. B cell-adapted EID of ocrelizumab increased the mean time until next infusion from 27.3 to 46.1 weeks. Ig levels declined significantly in the SID group over 12 months but not in the EID group. Previously stable patients remained stable under EID as measured by expanded disability status scale (EDSS), neurofilament light chain, timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT), symbol digit modalities test (SDMT), and multiple sclerosis impact scale (MSIS-29).
CONCLUSIONS
CONCLUSIONS
In our pilot study, B cell-adapted EID of ocrelizumab prevented the decline of Ig levels without affecting disease activity in previously stable patients with MS. Based on these findings, we propose a new algorithm for long-term ocrelizumab treatment.
FUNDING
BACKGROUND
This study was supported by the Deutsche Forschungsgemeinschaft (SFB CRC-TR-128, SFB 1080, and SFB CRC-1292) and the Hertie Foundation.
Identifiants
pubmed: 37236189
pii: S2666-6340(23)00141-1
doi: 10.1016/j.medj.2023.05.001
pii:
doi:
Substances chimiques
ocrelizumab
A10SJL62JY
Antibodies, Monoclonal, Humanized
0
Immunoglobulin M
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-372.e3Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests F.Z. has recently received research grants and/or consultation funds from Biogen, Ministry of Education and Research (BMBF), Bristol-Meyers-Squibb, Celgene, German Research Foundation (DFG), Janssen, Max-Planck-Society (MPG), Merck Serono, Novartis, Progressive MS Alliance (PMSA), Roche, Sanofi Genzyme, and Sandoz. S.B. has received honoraria and compensation for travel from Biogen Idec, Bristol Meyer Squibbs, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva.