Higher Ocrelizumab Exposure Linked to Greater Reduction in MS Disability Progression

Higher ocrelizumab serum levels are associated with reduced disability progression in patients with multiple sclerosis (MS), according to an analysis published in Neurology Neuroimmunology & Neuroinflammation.

In three phase 3 studies—OPERA I/II and ORATORIO—ocrelizumab improved both clinical and magnetic resonance imaging (MRI) measures of MS disease activity and progression, explained first author Stephen L Hauser, MD, of the University of California, San Francisco, and study coauthors.

“The magnitude of ocrelizumab treatment benefit on disability progression was greater in lighter vs heavier patients,” researchers wrote. “These observations suggest that higher ocrelizumab serum levels provide more complete B-cell depletion and a greater delay in disability progression.”

The post hoc analysis grouped study participants from OPERA I/II and ORATORIO into exposure quartiles based on their serum ocrelizumab level over the treatment period.

Across all exposure subgroups, patients with relapsing or primary progressive MS had new MRI lesion counts reduced almost to undetectable levels with ocrelizumab, according to the study. In patients with relapsing MS, annualized relapse rates dropped to very low levels. Researchers reported a persistent trend of higher ocrelizumab exposure leading to lower rates of disability progression at 24 weeks. 

Across exposure subgroups, rates of infusion-related reactions, serious adverse events, and serious infections were steady, the study found.

“A consistent trend of higher ocrelizumab exposure leading to greater reduction in risk of confirmed disability progression was observed, particularly in the relapsing MS trials, and was not associated with a higher rate of adverse events,” researchers wrote. “Higher ocrelizumab exposure may provide improved control of disability progression by reducing disease activity below that detectable by annualized relapse rate and MRI, and/or by attenuating other B-cell–related pathologies responsible for tissue damage.”

Reference: 
Hauser SL, Bar-Or A, Weber MS, et al. Association of higher ocrelizumab exposure with reduced disability progression in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023;10(2):e200094. doi:10.1212/NXI.0000000000200094