Effect of ocrelizumab on leptomeningeal inflammation and humoral response to Epstein-Barr virus in multiple sclerosis. A pilot study.
Cognitive dysfunction
Epstein-Barr virus
Gray matter pathology
Leptomeningeal inflammation
Multiple sclerosis
Ocrelizumab
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
22
04
2022
revised:
15
06
2022
accepted:
05
08
2022
pubmed:
15
8
2022
medline:
10
11
2022
entrez:
14
8
2022
Statut:
ppublish
Résumé
Ocrelizumab is an effective treatment for relapsing and primary-progressive multiple sclerosis (MS). However, the effect of ocrelizumab on leptomeningeal (LM) inflammation is unknown. To investigate whether ocrelizumab reduces LM inflammation by reducing the exposure to Epstein-Barr virus (EBV)-infected B cells in relapsing-remitting (RR) MS. This was a Phase IV, prospective, open-label, single-center, observational, longitudinal pilot study of RRMS patients who started treatment with ocrelizumab (NCT03025269). Clinical, MRI and EBV-antibodies outcomes at baseline, 12- and 24-month of the study were evaluated. The MRI outcomes included T2, T1 and T1-contrast enhancing (CE) lesion counts and volumes, LM CE count, and percentage brain volume changes. 27 RRMS patients started ocrelizumab and 24 remained on the treatment for whole duration of the study. Most patients remained stable (74.1%) or improved (18.5%) in their disability status. At baseline, 42.3% of patients showed LM CE lesions. The majority of patients remained stable in their LM CE status over the follow-up (72.7%). A significant decrease in percentage volume loss of cortex (p=0.009), GM (p=0.01) and thalamus (p=0.038) was detected, while T1-LV increased (p=0.02). A significant decrease of EBNA-1 IgG (p=0.013) was evidenced. An infusion-related allergic reaction led to discontinuation of the medication in one patient at first dose. Treatment with ocrelizumab was safe and clinically effective. Brain volume loss and accumulation of T1-LV occurred. While ocrelizumab decreased humoral response to EBV possibly by reducing B cells, it did not reduce LM inflammation.
Sections du résumé
BACKGROUND
BACKGROUND
Ocrelizumab is an effective treatment for relapsing and primary-progressive multiple sclerosis (MS). However, the effect of ocrelizumab on leptomeningeal (LM) inflammation is unknown.
OBJECTIVE
OBJECTIVE
To investigate whether ocrelizumab reduces LM inflammation by reducing the exposure to Epstein-Barr virus (EBV)-infected B cells in relapsing-remitting (RR) MS.
METHODS
METHODS
This was a Phase IV, prospective, open-label, single-center, observational, longitudinal pilot study of RRMS patients who started treatment with ocrelizumab (NCT03025269). Clinical, MRI and EBV-antibodies outcomes at baseline, 12- and 24-month of the study were evaluated. The MRI outcomes included T2, T1 and T1-contrast enhancing (CE) lesion counts and volumes, LM CE count, and percentage brain volume changes.
RESULTS
RESULTS
27 RRMS patients started ocrelizumab and 24 remained on the treatment for whole duration of the study. Most patients remained stable (74.1%) or improved (18.5%) in their disability status. At baseline, 42.3% of patients showed LM CE lesions. The majority of patients remained stable in their LM CE status over the follow-up (72.7%). A significant decrease in percentage volume loss of cortex (p=0.009), GM (p=0.01) and thalamus (p=0.038) was detected, while T1-LV increased (p=0.02). A significant decrease of EBNA-1 IgG (p=0.013) was evidenced. An infusion-related allergic reaction led to discontinuation of the medication in one patient at first dose.
CONCLUSIONS
CONCLUSIONS
Treatment with ocrelizumab was safe and clinically effective. Brain volume loss and accumulation of T1-LV occurred. While ocrelizumab decreased humoral response to EBV possibly by reducing B cells, it did not reduce LM inflammation.
Identifiants
pubmed: 35964555
pii: S2211-0348(22)00602-2
doi: 10.1016/j.msard.2022.104094
pii:
doi:
Substances chimiques
ocrelizumab
A10SJL62JY
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104094Informations de copyright
Copyright © 2022. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interests Robert Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Janssen, Keystone Heart, Protembis and Novartis for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical, Dejan Jakimovski, Murali Ramanathan and Niels Bergsland have nothing to disclose, Ralph HB. Benedict has received consultation or speaking fees from Bristol Myer Squibb, Biogen, Merck, EMD Serono, Roche, Verasci, Immune Therapeutics, Novartis, and Sanofi-Genzyme, Michael G. Dwyer has received personal compensation from Keystone Heart for consultant fees. He received financial support for research activities from Bristol Myers Squibb, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical, Bianca Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi &Genzyme, Genentech, Novartis, BMS, Bayer, Horizon and Janssen. Dr Weinstock-Guttman received research funds from Biogen Idec, Genentech and Novartis.