Ocrelizumab demonstrated superiority over placebo in delaying disability progression in primary progressive multiple sclerosis (PPMS), including in older patients and those with more advanced disease, according to results from the ORATORIO-HAND trial published in The Lancet. The study, a multicenter, double-blind, randomized, placebo-controlled phase 3b trial, found a stronger effect on hand function with a manageable safety profile.
These findings broaden the potential population that may benefit from the therapy, which is currently approved for PPMS and relapsing forms of MS. The trial specifically enrolled patients often excluded from earlier studies—those over 55 or with higher baseline disability—addressing a significant gap in clinical evidence.
Separately, the MUSETTE and GAVOTTE trials tested a bodyweight-adjusted higher dose of ocrelizumab in relapsing MS and PPMS, respectively. In both studies, the higher dose did not further improve control of disability progression compared to the standard dose, and no new safety concerns emerged, suggesting the current dosing regimen remains optimal.
The ORATORIO-HAND results could shift treatment paradigms for PPMS, a form of the disease with few approved options. However, the lack of benefit from dose escalation may temper expectations for more aggressive therapy in patients with breakthrough disease.
Experts caution that while the data are compelling, the translation to real-world outcomes requires longer follow-up, and cost-benefit analyses will be needed to guide clinical adoption.