Higher blood levels of Ocrevus lower confirmed disability progression risk
Trials' data also show no link between greater therapy exposure, side effects
Higher blood levels of Ocrevus (ocrelizumab) is associated with a significantly lower risk of confirmed disability progression during treatment in people with relapsing and progressive forms of multiple sclerosis (MS), according to an analysis of data from three Phase 3 clinical trials.
Notably, the lower disability progression rates reported in people with higher Ocrevus exposure were independent of reductions in relapse rates or MRI activity, suggesting the medication worked to prevent progression independent of relapse activity (PIRA).
Higher Ocrevus exposure also was not linked to more side effects.
The study, “Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis,” was published in Neuroimmunology & Neuroinflammation.
Higher blood levels likely lead to ‘more complete’ B-cell depletion
MS is an inflammatory disease where damage to the nervous system results in such disease symptoms as muscle weakness and difficulty walking.
Ocrevus, an approved MS treatment, works to eliminate B-cells, a type of white blood cell that plays a role in MS. By lowering the number of B-cells, the medication is expected to ease MS symptoms and slow disease progression.
In clinical trials, Ocrevus was highly effective at lowering the number of relapses and preventing the development of new lesions in people with relapsing forms of MS. It also significantly reduced disability progression in relapsing MS and in people with primary progressive MS (PPMS).
Trial results also linked higher blood levels of Ocrevus to fewer B-cells in circulation, which can improve disease outcomes. Of note, Ocrevus’ impact on disability progression was more pronounced in lighter than heavier patients.
“A plausible explanation for this observation could be that higher [Ocrevus] exposure in lighter patients leads to more complete B-cell depletion and to a more pronounced delay in disability progression,” the researchers wrote.
A team of researchers in the U.S., in collaboration with Roche, the treatment’s developer, set out to better understand the association between Ocrevus exposure and confirmed disability progression.
They examined data from 1,267 patients who took part in the OPERA I (NCT01247324) and OPERA II (NCT01412333) clinical trials, which supported Ocrevus’ approval for relapsing forms of MS, and the ORATORIO (NCT01194570), which led to its approval for PPMS.
Participants were divided into four groups based on their exposure to Ocrevus, or the medication’s levels in blood samples.
Ocrevus led to dramatic reductions in relapse rates and in the number of lesions with active inflammation. But there were no differences between exposure groups, indicating a ceiling effect — in which increased exposure does not result in additional benefits.
“We found that for most measures reflecting relapsing disease biology, including clinical [annual relapse rate] and MRI (new lesion) outcomes, no association with [Ocrevus] exposure could be observed,” the researchers wrote. “This is potentially due to treatment-related reduction of these inflammatory pathology-related measures to such low levels that the effect size is no longer exposure-dependent (ceiling effect).”
However, confirmed disability progression (CDP) — defined as an increase in Expanded Disability Status Scale (EDSS) scores lasting at least six months — was less frequent and later in time among patients in the highest exposure groups relative to those with lower exposure.
These associations were only significant in the relapsing MS trials, but similar trends were seen in people with PPMS, the researchers noted.
Higher exposure to Ocrevus was not linked to higher rates of severe side effects, infections, or infusion-related reactions.
“A consistent trend of higher ocrelizumab exposure leading to greater reduction in risk of CDP was observed, particularly in the relapsing MS trials, and was not associated with a higher rate of adverse events,” the researchers wrote.
Together, the results suggest that “higher ocrelizumab exposure may provide improved control of disability progression by reducing disease activity below that detectable by [relapse rates] and MRI, and/or by attenuating other B-cell–related [disease mechanisms] responsible for tissue damage,” the researchers concluded.