Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS

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 (IFN beta 1a)/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 IFN beta 1a (p < 0.001) or placebo (p < 0.001). Conclusion: Ocrelizumab effectively reduced thalamic volume loss compared with IFN beta 1a/placebo. Early treatment effects on thalamic tissue preservation persisted over time. Thalamic volume loss could be a potential sensitive marker of persisting tissue damage.

Automated summary

Ocrelizumab significantly reduces thalamic volume loss in patients with multiple sclerosis, and the protective effect on thalamic tissue preservation persists over time.