Less thalamic atrophy in patients initiating ocrelizumab earlier

In the open-label extension (OLE) of the phase 3 trials OPERA I/OPERA II and ORATORIO, patients with relapsing and primary progressive MS who were initially randomised to ocrelizumab experienced less thalamic volume loss than those initiating ocrelizumab later [1]. Baseline thalamic volume may predict confirmed disability progression (CDP) and CDP-9-Hole Peg Test (9HPT) score in relapsing MS.

Thalamic atrophy occurs early and consistently over the course of MS, at a rate that is faster than in healthy controls. MS has both a direct effect on the thalamus by neuronal loss, and an indirect effect due to axonal transection in lesions which affects afferent and efferent projections of the thalamus. Thalamic atrophy may therefore be a useful marker of therapeutic effects. This study assessed the efficacy of switching to or maintaining ocrelizumab therapy on thalamic atrophy in patients with relapsing and primary progressive MS participating in OPERA I/II and ORATORIO, and evaluated if baseline thalamic volume predicts disability progression during the double-blind period of both trials.

The OPERA I/II trials compared ocrelizumab (n=827) to interferon β-1a (n=829) in relapsing MS patients; ORATORIO compared ocrelizumab (n=488) to placebo (n=244) in primary progressive MS patients.

Ocrelizumab significantly reduced thalamic atrophy in patients who were initially randomised to ocrelizumab compared with those initiating ocrelizumab later (all P<0.001; see Table). The correlation of thalamic volume with CDP as measured by 9HPT, EDSS, and timed 25-feet walk was significant in both trials, albeit modest.

Table: Percentage change in thalamic volume from baseline in OLE of OPERA I/II and ORATORIO trials [1]



IFN β-1a, interferon β-1a; OCR, ocrelizumab; PBO, placebo; OLE, open-label extension.

1. Arnold D, et al. Reduced thalamic atrophy in patients initiating earlier versus delayed ocrelizumab therapy: results from the OLE of OPERA I/II and ORATORIO. MSVirtual 2020, Abstract FC03.05.

Posted on 25 November 202025 March 2024