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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Cognitive and structural brain changes in ofatumumab-treated multiple sclerosis: A longitudinal study.

Aurora Zanghì1, Paola Sofia Di Filippo1, Carlo Robusto1

  • 1BRAND (Breakthrough Research in Autoimmune and Neurodegenerative Diseases) Research Center, Department of Medical and Surgical Sciences, University of Foggia, Italy.

Neurotherapeutics : the Journal of the American Society for Experimental Neurotherapeutics
|June 3, 2026
PubMed
Summary

Ofatumumab treatment in relapsing multiple sclerosis (RMS) shows persistent but slowing brain atrophy and improved cognition. Specific patient subgroups may experience structure-cognition coupling, indicating personalized treatment needs.

Keywords:
Brain atrophyCognitive impairmentMultiple sclerosisNeurodegenerationOfatumumab

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Area of Science:

  • Neuroscience
  • Immunology
  • Radiology

Background:

  • Anti-CD20 therapies are effective against multiple sclerosis (MS) inflammation.
  • Real-world data on neurodegeneration and cognition during anti-CD20 treatment is limited.
  • Ofatumumab is an anti-CD20 therapy used for relapsing MS (RMS).

Purpose of the Study:

  • To assess the long-term effects of ofatumumab on neurodegeneration and cognitive function in RMS patients.
  • To investigate the association between brain structure changes and cognitive performance.
  • To identify patient subgroups where structural changes impact cognition.

Main Methods:

  • Longitudinal observational study of 85 RMS patients treated with ofatumumab.
  • Cognitive assessment using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), focusing on processing speed (Symbol Digit Modalities Test).
  • Brain structure analysis using Magnetic Resonance Imaging (MRI) for thalamic volume, deep gray matter (DGM) volume, and cortical thickness (CTh).
  • Linear mixed-effects models were used to analyze longitudinal changes and structure-cognition associations.

Main Results:

  • Brain atrophy persisted but attenuated after 12 months of ofatumumab treatment.
  • Significant improvements were observed in processing speed (SDMT) and memory functions.
  • No global longitudinal association between brain structure and cognition was found.
  • Thalamic atrophy correlated with SDMT decline in patients with Expanded Disability Status Scale ≥3.
  • Deep gray matter atrophy correlated with cognitive decline in patients with a baseline SDMT z-score ≤ -1.

Conclusions:

  • Ofatumumab treatment in RMS may preserve cognitive function despite ongoing, but slowing, neurodegeneration.
  • Structural-functional coupling between brain atrophy and cognitive decline emerges in vulnerable patient subgroups.
  • These findings highlight the need for personalized monitoring and treatment strategies in MS.