To assess the effect of ocrelizumab versus interferon beta-1a (IFNβ1a)/placebo on thalamic atrophy in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), in the Phase III OPERA I (NCT01247324), OPERA II (NCT01412333) and ORATORIO (NCT01194570) trials, respectively.

During the double-blind treatment phase of OPERA I, OPERA II and ORATORIO, change in thalamic volume was computed using Jacobian integration and analyzed using a mixed-effect repeated measurement model, adjusted for baseline volume, age, region (US vs rest of the word), Expanded Disability Status Scale (EDSS) category (<4, ≥4), time, treatment, interaction between treatment and time, and between treatment and baseline volume.

Mean baseline normalized thalamic volume was 15.1 cm³ in RMS and 14.4 cm³ in PPMS. Changes from baseline (%) for IFNβ1a/ocrelizumab at Week 24, 48 and 96, respectively, were: RMS, –1.54/–0.82 (p<0.001), –2.17/–1.28 (p<0.001), –2.91/–1.67 (p<0.001) for placebo/ocrelizumab at Week 24, 48 and 120, respectively; PPMS, –0.80/–0.75 (p=0.574), –1.29/–1.06 (p=0.069), –2.59/–1.67 (p<0.001).

Ocrelizumab progressively slowed thalamic atrophy in both patients with RMS and patients with PPMS, compared with the comparator arm. The immediate effect observed in RMS could be attributed to pseudoatrophy affecting patients treated with IFNβ1a. Thalamic atrophy may be a sensitive measure of treatment effect.