Ocrelizumab Reduces Risk of Upper Extremity Disability in PPMS Patients


In using the EDSS and 9HPT scales as a metric for the therapy’s influence on disability risk reduction, the investigators were additionally providing context to ocrelizumab’s benefits for ambulation rates and MS-related costs.

Edward J. Fox, MD

Edward J. Fox, MD

A new assessment of ocrelizumab (Ocrevus) in patients with primary progressive multiple sclerosis (PPMS) has found the monoclonal antibody has capability to reduce patient risk of upper extremity (UE) disability progression.

In new findings from the phase 3 randomized ORATORIO trial, investigators analyzed ocrelizumab versus placebo in an intent-to-treat patient population stratified by Nine-Hole Peg Test (9HPT) and Expanded Disability Status Scale (EDSS) scores at baseline. Assessing for reduced risk of disability progression remains a focal point for progressing MS care.

Led by Edward J. Fox, MD, of Penn State Health, the team emphasized how the rare MS subtype PPMS is characterized by the gradual debilitation of patient neurological ability that could affect their everyday motor, sensory, coordination, and cognitive function.

UE impairment impacts patients’ ability to perform activities of daily living, affecting their independence and quality of life,” investigators wrote. “Moreover, the association of UE dysfunction and unemployment in patients with MS highlights the economic impact of compromised hand/arm function in MS.”

Ocrelizumab, from Genentech, was first approved by the US Food and Drug Administration (FDA) for the treatment of relapsing-remitting MS (RRMS) and PPPMS in March 2017—making history as the first therapy indicated for the latter MS subtype. Its approval was partially based on previous results to come from the ORATORIO trial series.

In using the EDSS and 9HPT scales as a metric for the therapy’s influence on disability risk reduction, the investigators were additionally providing context to ocrelizumab’s benefits for ambulation rates and MS-related costs, as both tests provide context to either facet. A clinically meaningful change in 9HPT time is commonly defined as an increase of ≥20%.

A total of 732 patients were split 2:1 to either 600mg ocrelizumab (n= 488) or placebo (n= 244) every 24 weeks for ≥120 weeks. They were administered the 9HPT test at baseline and every 12 weeks thereafter, with both hands being tested individually twice. Investigators assessed for endpoints including change in 9HPT time, and the proportion of patients with confirmed progression of ≥20% in the test.

Mean baseline 9HPT times for both hands, dominant and non-dominant hand were comparable across both treatment groups, but notably higher in the ocrelizumab treatment group with baseline EDSS ≥6 (indicating a significant walking impairment) versus those on placebo.

Ocrelizumab significantly reduced the risk of 12- and 24-week confirmed progression of ≥20% in 9HPT time versus placebo for both hands (HR = 0.56, P < .001; HR = .55, P < .001, respectively). Risk reductions were noted in the treated patients’ dominant (HR = 0.72, P = .046) and non-dominant hands (HR = 0.63, P = .005)—albeit slightly less significant.

Change in 9HPT time from baseline to Week 120 was significantly improved among patients on ocrelizumab versus those on placebo across tests for both hands and the non-dominant hand, with a numerically consistent trend reported for dominant hands tests. Among treated patients with abnormal 9HPT times at baseline, the improvement to Week 120 versus placebo was significantly across all hands tests.

Though investigators advised the results be considered with limitations including the need for more comprehensive analysis into the benefit of ocrelizumab in preventing UE impairment progression in patients with PPMS—particular in those who are already wheelchair-confined&mdash;they argue the results support the need for further 9HPT analysis in patients with PPMS. Their proposal echoes the suggestion that ‘no evidence of disease activity’ (NEDA) be replaced by ‘no evidence of progression and active diseases’ (NEPAD) in MS assessment, as the latter definition integrates 9HPT results and ambulation analysis.

“Ocrelizumab was shown to enhance the proportion of PPMS patients achieving NEPAD by threefold compared with placebo,” investigators noted.

As 9HPT performance has also been linked to differing rates of cortical atrophy in patients with progressive MS, investigators called for long-term outcome analysis to understand more of the links that constitute the comprehensive burden of PPMS on its patients.

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