Ocrevus Helps Preserve Hand and Arm Function in PPMS Patients, Trial Data Show
Treating primary progressive multiple sclerosis (PPMS) patients with Ocrevus (ocrelizumab) can help to preserve strength and function in their hands and the arms, analysis of data from a Phase 3 trial found.
The research, “Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial,” was published in the Multiple Sclerosis Journal.
A gradual loss of function and dexterity in the upper extremities — the hands and the arms — is common to all MS patients, but thought to be particularly prevalent in those with progressive disease. Given the importance of upper extremity (UE) use to these patients, particularly those with walking and gait limitations, maintaining hand and arms function is key to a quality life, employment, and independence.
Doctors and researchers need to assess UE function in patients to monitor disease progression and evaluate the potential benefit of treatments.
Despite being a commonly used measure of MS disability, many consider the Expanded Disability Status Scale (EDSS) less than adequate in assessing a patient’s upper extremities, particularly in progressive MS.
The Multiple Sclerosis Functional Composite (MSFC) was designed to address EDSS limitations by including quantitative assessments of ambulation, UE function — using the Nine-Hole Peg Test (9HPT) — and cognition.
The 9HPT consists of a container with nine pegs, and a wood or plastic block with nine empty holes. A seated patient picks up the nine pegs and, one at a time, as quickly as possible places them in the holes. Then, again as quickly as possible, the patient removes the pegs from the holes, returning them to the container. Time needed to complete the task is recorded.
A randomized, double-blind, and placebo-controlled Phase 3 trial, ORATORIO (NCT01194570; study funded by Roche, which owns Genentech) enrolled 732 PPMS patients, ages 18–55. Treatment with Ocrevus led to lower rates of disease progression, as assessed at 12 and 24 weeks based on EDSS, the timed 25-foot walk, brain lesion volume, and total brain volume loss.
Now, in an exploratory analysis, researchers looked specifically at the effects of Ocrevus on UE dysfunction in these patient.
In the 120-week ORATORIO trial, the 9HPT was administered at baseline (study’s start) and every 12 weeks thereafter. Both hands were tested twice, the dominant hand first. Goals analyzed included changes in the time needed to finish the 9HPT, and the proportion of patients with confirmed progression of 20% or greater in this peg test — the usual threshold for clinically meaningful change in this test.
Researchers analyzed results of the entire patient group, as well as in patient subgroups: those with an abnormal or impaired (more than 25 seconds) 9HPT score at baseline compared to those with a normal score (25 seconds or less), and patients with an EDSS score of 6.0 or greater, corresponding to significant walking impairment and needing at least a cane to walk any distance.
As previously shown, treatment with Ocrevus reduced the risk of confirmed progression of 20% or greater in 9HPT time for both hands at 12 and 24 weeks, both in the overall patient population and in patients with abnormal 9HPT times at baseline. Similar differences were found at higher confirmed progression thresholds (25%, 30%, and 35%, meaning higher UE disability).
Data further revealed a “significantly improved” change in 9HPT time from baseline to week 120 in patients treatted with Ocrevus compared to those given placebo. This benefit was consistent in 9HPT and EDSS subgroup analyses.
Overall, “findings from this analysis showed that ocrelizumab [Ocrevus] mitigated progression of UE impairment in patients with PPMS using the 9HPT,” the researchers wrote.
The team also noted that Ocrevus’ benefits in PPMS need to be determined in wheelchair-confined patients, for whom maintaining hand-arm function is of utmost importance.
Roche, together with a steering committee, is responsible for the trial’s design and its data analysis.