Deformation-based morphometry identifies deep brain structures protected by ocrelizumab

Abstract

Background: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. Methods: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy. Results: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.05), a humanized anti-CD20 + monoclonal antibody approved for the treatment of multiple sclerosis. Additionally, identified brainstem shrinkage, as well as brain ventricle expansion, was associated with a greater risk for confirmed disability progression (p < 0.05). Conclusions: The identification of deep brain structures has a strong implication for developing new biomarkers of brain atrophy reduction to advance drug development for multiple sclerosis, which has an increasing focus on targeting the progressive biology.

Keywords

• Deformation-based morphometry
• Brain atrophy
• Multiple sclerosis
• Biomarkers
• Ocrelizumab