Author Of 1 Presentation
P0613 - Ocrelizumab Reduces Regional Brain Atrophy in Relapsing Multiple Sclerosis as Assessed by Longitudinal Deformation-based Morphometry (ID 1228)
Abstract
Background
Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS). It has been reported that OCR reduces brain atrophy in MS patients, however, a voxel-based approach has never been reported.
Objectives
To identify brain regions where atrophy is modified by the OCR treatment in Relapsing MS (RMS), using a fully automatic, voxel-based approach.
Methods
We applied longitudinal deformation-based morphometry (L-DBM) using the Advanced Normalization Tools (ANTs) to T1-weighted 3D MPRAGE brain MRI (voxel=1x1x3 mm3 ) from two clinical trials of OCR for RMS (Opera I: NCT01247324 and Opera II: NCT01412333). For each MRI visit, a Jacobian map was derived based on the deformation generated by registering the scan to a Single-Subject Template (SST) constructed for the same patient. Jacobian maps in patient SSTs were mapped to a population brain template for group analysis. Patients were included if MRI data were available for all visits (baseline, Weeks 24, 48, and 96) and the images were of sufficient quality to be successfully processed through the L-DBM pipeline (683 in the OCR arm, 580 in the active control arm of Interferon beta-1a). Voxelwise ANOVA was iterated over the whole brain to detect an interaction between Treatment and Time (p<0.01 with familywise error correction). Post-hoc analysis was done with mean Jacobian of identified regions, including Linear Mixed Effect (LME) analysis.
Results
Voxelwise ANOVA identified one cluster of voxels in the brain (besides the ventricles) that were contained within parts of thalamus, brainstem, and cerebellum. From the analysis of mean Jacobian of this cluster region, the percent volume reduction from baseline was significantly smaller in the treatment arm than the control arm at every follow-up visit (p<0.0001, t>8.0, relative difference>75%). LME analysis of the mean Jacobian of the cluster region confirmed that there was a strong interaction between Treatment and Time (F=18.35), for which age and sex were controlled.
Conclusions
L-DBM has identified several brain structures where atrophy was modified by the OCR treatment in RMS. The L-DBM analysis was performed at the voxel level and these regional findings are consistent with previous reports. Localization of the treatment-responsive brain structures may have an implication for future assessment of clinical outcomes in MS.