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

  • Robert Zivadinov
    Correspondence
    Corresponding author at: Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA.
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA

    Center for Biomedical Imaging at Clinical and Translational Science Institute, University of Buffalo, State University of New York, NY, USA
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  • Dejan Jakimovski
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA
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  • Murali Ramanathan
    Affiliations
    Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA
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  • Ralph HB. Benedict
    Affiliations
    Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA
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  • Niels Bergsland
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA
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  • Michael G. Dwyer
    Affiliations
    Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA

    Center for Biomedical Imaging at Clinical and Translational Science Institute, University of Buffalo, State University of New York, NY, USA
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  • Bianca Weinstock-Guttman
    Affiliations
    Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA
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Published:August 06, 2022DOI:https://doi.org/10.1016/j.msard.2022.104094

      Highlights

      • This study investigated the effect of ocrelizumab on leptomeningeal (LM) inflammation in multiple sclerosis (MS).
      • The hypothesis was that reduction in the exposure to Epstein-Barr virus (EBV)-infected B cells would lead to decrease in LM inflammation.
      • The majority of patients remained stable in their LM CE status over the follow-up (72.7%).
      • A significant decrease of EBNA-1 IgG (p=0.013) was evidenced.
      • Ocrelizumab decreased humoral response to EBV possibly by reducing B cells, it did not reduce LM inflammation.

      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.

      Keywords

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