Effect of Deflazacort and Prednisone versus Placebo on Muscle Strength in Boys with Duchenne Muscular Dystrophy Who Have Lost Ambulation: Results from the Deflazacort Clinical Trial Program

source: American Academy of Neurology

year: 2016

authors: Timothy Cunniff, Stephen Wanaski, Jordan Dubow, James Meyer

Objective:
To assess the effects of deflazacort and prednisone on muscle strength in boys with DMD who have lost ambulation

Background:
Duchenne Muscular Dystrophy (DMD) is the most common type of muscular dystrophy. Glucocorticoids are the mainstay of treatment in ambulatory patients, but often discontinued after boys have lost ambulation.

Design/Methods:
This randomized, double-blind, placebo-controlled, active comparator, Phase 3 study evaluated the efficacy of two deflazacort doses (0.9 mg/kg/day and 1.2 mg/kg/day) compared to prednisone (0.75 mg/kg/day) and placebo for treatment of boys with DMD. The first segment compared deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of deflazacort to prednisone from 12 to 52 weeks. We conducted a post-hoc subgroup analysis of muscle strength (using a modified 11-point medical research council scale) in patients who were non-ambulatory at baseline.

Results:
A total of 196 participants were randomized to the 4 treatment groups; 45 patients were non-ambulatory at baseline. At 12 weeks, both doses of deflazacort and prednisone had numerical improvement in muscle strength while placebo patients worsened. Deflazacort at 1.2 mg/kg/day reached significance over placebo at 12 weeks (LS mean change of 0.49; p<0.05). Over 52 weeks of treatment, both deflazacort groups showed numerical improvement in muscle strength while the prednisone group worsened [LS mean change vs. prednisone of 0.27 for deflazacort 0.9 mg/kg/day (p=0.387) and 0.45 for deflazacort 1.2 mg/kg/day (p=0.088)].

Conclusions:
This is the first prospective, randomized, blinded study to demonstrate the effects of deflazacort and prednisone on muscle strength in non-ambulatory boys with DMD. In this small, sub-set analysis, deflazacort demonstrated trends in improving muscle strength in boys who had lost ambulation. Although the recommended dose of deflazacort is 0.9 mg/kg/day, increased doses may be required to preserve motor function in post- ambulatory boys; these data merit further investigation.