Faculty, Staff and Student Publications
Publication Date
10-1-2022
Journal
Multiple Sclerosis Journal
Abstract
Background: In multiple sclerosis (MS), thalamic integrity is affected directly by demyelination and neuronal loss, and indirectly by gray/white matter lesions outside the thalamus, altering thalamic neuronal projections.
Objective: To assess the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ1a)/placebo on thalamic volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II; NCT01247324/NCT01412333) and in primary progressive MS (PPMS, ORATORIO; NCT01194570).
Methods: Thalamic volume change was computed using paired Jacobian integration and analyzed using an adjusted mixed-effects repeated measurement model.
Results: Over the double-blind period, ocrelizumab treatment significantly reduced thalamic volume loss with the largest effect size (Cohen's d: RMS: 0.561 at week 96; PPMS: 0.427 at week 120) compared with whole brain, cortical gray matter, and white matter volume loss. At the end of up to 7 years of follow-up, patients initially randomized to ocrelizumab still showed less thalamic volume loss than those switching from IFNβ1a (p < 0.001) or placebo (p < 0.001).
Conclusion: Ocrelizumab effectively reduced thalamic volume loss compared with IFNβ1a/placebo. Early treatment effects on thalamic tissue preservation persisted over time. Thalamic volume loss could be a potential sensitive marker of persisting tissue damage.
Keywords
Antibodies, Monoclonal, Humanized, Clinical Trials, Phase III as Topic, Double-Blind Method, Humans, Immunologic Factors, Interferon beta-1a, Magnetic Resonance Imaging, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Randomized Controlled Trials as Topic, Ocrelizumab, multiple sclerosis, thalamus, atrophy, treatment outcome
DOI
10.1177/13524585221097561
PMID
35672926
PMCID
PMC9493406
PubMedCentral® Posted Date
6-7-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes