Effect of ocrelizumab on leptomeningeal inflammation and humoral response to Epstein-Barr virus in multiple sclerosis. A pilot study.

Abstract

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:

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:

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:

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:

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.

• Authors: Robert Zivadinov, Dejan Jakimovski, Murali Ramanathan, Ralph Hb Benedict, Niels Bergsland, Michael G Dwyer, Bianca Weinstock-Guttman
• Journal: Multiple sclerosis and related disorders (Mult Scler Relat Disord) Vol. 67 Pg. 104094 (Nov 2022) ISSN: 2211-0356 [Electronic] Netherlands
• PMID: 35964555 (Publication Type: Observational Study, Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• ocrelizumab

Topics

• Humans
• Multiple Sclerosis (pathology)
• Herpesvirus 4, Human
• Pilot Projects
• Epstein-Barr Virus Infections (complications, drug therapy)
• Prospective Studies
• Multiple Sclerosis, Relapsing-Remitting (diagnostic imaging, drug therapy)
• Inflammation