Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. (October 2022)

• Record Type: Journal Article
• Authors: Arnold, Douglas L; Sprenger, Till; Bar-Or, Amit; Wolinsky, Jerry S; Kappos, Ludwig; Kolind, Shannon; Bonati, Ulrike; Magon, Stefano; van Beek, Johan; Koendgen, Harold; Bortolami, Oscar; Bernasconi, Corrado; Gaetano, Laura; Traboulsee, Anthony
• Is Part Of: Multiple sclerosis. Volume 28:Number 12(2022)
• Page Start: 1927
• Page End: 1936
• Publication Date: 2022-10
• Subjects: Ocrelizumab -- multiple sclerosis -- thalamus -- atrophy -- treatment outcome; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/13524585221097561
• Languages: English
• ISSNs: 1352-4585

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.