Ocrelizumab Reduces Upper Extremity Disability Progression Risk in PPMS

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hands nervous
Investigators observed that monoclonal antibody ocrelizumab may reduce the risk for upper extremity disability progression in patients with primary progressive multiple sclerosis.

Ocrelizumab, a recombinant humanized monoclonal antibody, is associated with a noticeably reduced risk for progression of upper extremity (UE) disability compared with placebo in patients with primary progressive multiple sclerosis (PPMS), according to study results published in Multiple Sclerosis Journal. In addition, researchers from the phase 3 study found that ocrelizumab was associated with a greater improvement in PPMS relative to placebo.

Patients with PPMS were randomly assigned to either 600 mg ocrelizumab (n=488) or placebo (n=244). Treatment, which was provided as 2 intravenous infusions of 300 mg 14 days apart, and placebo were administered every 24 weeks for ≥120 weeks. Researchers assessed UE function using the 9-Hole Peg Test (9HPT) at baseline and every 12 weeks. Exploratory end points included the change in 9HPT time and the percentage of patients with confirmed progression (CP) in UE impairment of ≥20%. Subgroup populations were stratified by baseline 9HPT time and Expanded Disability Status Scale score, with post hoc analyses including the proportion of patients who achieved more severe CP thresholds and those achieving confirmed improvement (CI) in 9HPT.

In the intention-to-treat population, ocrelizumab reduced the risk for CP ≥20% in 9HPT time for both hands vs placebo at 12 weeks (hazard ratio [HR] 0.56; P <.001) and 24 weeks (HR 0.55; P <.001). In patients with abnormal 9HPT times at baseline, treatment with ocrelizumab was associated with a greater reduction in risk for 24-week CP of ≥20% for both hands when compared with placebo (HR 0.54; P =.003). Similar benefits were also observed for ocrelizumab vs placebo in reducing the risk for disability progression for the worse hand (HR 0.64; P =.021). In addition, 9HPT time from baseline to 120-week follow-up improved significantly in the ocrelizumab vs placebo group for both hands (difference in adjusted means, −5.749±1.720; P <.001) and the worse hand (difference in adjusted means, –7.572±3.686; P =.041).

“The findings presented further support the need to use the 9HPT in routine clinical practice, particularly for patients with progressive MS, as a fit-for-purpose treat-to-target instrument to complete assessment of the target disability picture,” the researchers wrote. “Future analyses of long-term outcomes are needed to elucidate the relative importance of longitudinal change in regional [cortical grey matter volume vs] chronic [central nervous system] axonal/myelin tissue loss in [normal-appearing white matter], change in meningeal inflammation or acute [vs] chronic white matter, and/or cortical lesion activity to predict progressive worsening of UE function as measured by 9HPT.”

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Fox EJ, Markowitz C, Applebee A, et al. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler. 2018;24(14):1862-1870.