Short- and long-term effects of early versus delayed treatment with ocrelizumab on cerebellar volume loss in patients...

The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model.

In RMS, ocrelizumab reduced cerebellar volume loss in the double-blind period (DBP) and the difference (30% at DBP end) was maintained in the open-label extension (OLE) after control patients (IFN β-a) were switched to ocrelizumab. In PPMS, there was a small numerical difference in the DBP, but a larger (up to 22%) difference in favor of ocrelizumab in the OLE.

In both RMS and PPMS, early treatment with ocrelizumab helps to prevent additional cerebellar volume loss compared with delayed switching to ocrelizumab. Further analysis is needed to fully understand the clinical impact of cerebellar atrophy.