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Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS
Douglas L Arnold1, Till Sprenger2, Amit Bar-Or3
1Montreal Neurological Institute, McGill University, Montreal, QC, Canada/NeuroRx Research, Montreal, QC, Canada.
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.
Insights
Ocrelizumab significantly reduced thalamic volume loss in multiple sclerosis (MS) patients compared to interferon beta-1a or placebo. These protective effects on brain tissue persisted over long-term follow-up.
Area of Science:
- Neuroimmunology
- Neurodegeneration
- Clinical Neurology
Background:
- Multiple sclerosis (MS) impacts thalamic integrity through demyelination, neuronal loss, and lesions in surrounding gray/white matter.
- These pathological processes disrupt thalamic neuronal projections, affecting overall brain function.
Purpose of the Study:
- To evaluate the efficacy of ocrelizumab versus interferon beta-1a (IFNβ1a)/placebo in mitigating thalamic volume loss in relapsing MS (RMS) and primary progressive MS (PPMS).
- To assess the long-term impact of switching to ocrelizumab on thalamic volume changes in patients from the OPERA I/II and ORATORIO trials.
Main Methods:
- Thalamic volume changes were quantified using paired Jacobian integration.
- Statistical analysis employed an adjusted mixed-effects repeated measurement model to compare treatment groups.
Main Results:
- Ocrelizumab significantly reduced thalamic volume loss in both RMS and PPMS patients, demonstrating larger effect sizes compared to whole brain, cortical gray matter, and white matter volume loss.
- Over up to 7 years of follow-up, patients maintained on ocrelizumab exhibited significantly less thalamic volume loss than those who switched from IFNβ1a or placebo (p < 0.001).
Conclusions:
- Ocrelizumab effectively preserves thalamic volume compared to IFNβ1a/placebo in MS patients.
- The observed treatment benefits on thalamic tissue preservation are sustained over extended periods.
- Thalamic volume loss may serve as a sensitive biomarker for ongoing tissue damage in MS.
