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The ocrelizumab wearing-off phenomenon is associated with reduced immunomodulatory response and increased neuroaxonal

Isabel Monteiro1,2,3, Valerio Nicolella4, Mariano Fiorenza5

  • 1Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, Naples, Italy.

Journal of Neurology
|May 22, 2024
PubMed
Abstract

Insights

Wearing-off is common in multiple sclerosis (MS) patients on ocrelizumab, linked to higher T lymphocytes and neuroaxonal damage, suggesting a reduced treatment response.

Area of Science:

  • Neuroimmunology
  • Clinical Neurology
  • Biomarker Research

Background:

  • The wearing-off phenomenon, a decline in treatment efficacy between doses, is frequently observed in multiple sclerosis (MS) patients.
  • Ocrelizumab is a B-cell depleting therapy commonly used for MS, but its impact on wearing-off requires further investigation.
  • Understanding factors associated with wearing-off is crucial for optimizing MS management.

Purpose of the Study:

  • To assess the prevalence and severity of the wearing-off phenomenon in MS patients treated with ocrelizumab.
  • To identify demographic, clinical, immunological, and neuroaxonal damage markers associated with ocrelizumab-related wearing-off.
  • To explore the relationship between wearing-off symptoms and specific patient characteristics and biological markers.

Main Methods:

  • A cross-sectional study involving 106 MS patients on ocrelizumab for at least one year.
  • Wearing-off symptoms were assessed using a questionnaire between 21-23 weeks post-infusion.
  • Peripheral blood samples were analyzed for lymphocyte subpopulations via flow cytometry and plasma neurofilament light chain (pNfL) levels using immunoassay.

Main Results:

  • Over half (57.6%) of MS patients experienced wearing-off, with cognitive, sensory, and balance issues being most common.
  • Wearing-off was significantly associated with elevated plasma neurofilament light chain (pNfL) levels, indicating increased neuroaxonal damage.
  • Higher counts of CD8, CD3, and CD3CD27 lymphocytes correlated with the presence of wearing-off, while pNfL and CD8 counts were linked to severity.

Conclusions:

  • Wearing-off is a prevalent issue in MS patients treated with ocrelizumab.
  • The phenomenon is associated with markers of reduced immunomodulation (higher T lymphocyte counts) and increased neuroaxonal damage (higher pNfL).
  • These findings suggest that wearing-off may indicate a suboptimal treatment response to ocrelizumab in certain MS patients.
Keywords:
LymphocyteMultiple sclerosisNeurofilamentOcrelizumabWearing-off

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