Deflazacort in Duchenne dystrophy: Study of long‐term effect

Abstract

A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P < 0.01), in rising from a chair, Gower's maneuver, and walking (P < 0.0025) after 6 months of treatment. After 1 year, all the above changes remained significantly improved and the MRC index was significantly better (P < 0.05) in the treated group. After 2 years, a significant change was found in the MRC index: higher scores in walking, chair rising (P < 0.02), and grade and time of Gower's maneuver (P < 0.05) were found. The mean time for loss of ambulation for the treated group after we started the trial was 33.2 +/- 9 months; for the placebo group it was 20.5 +/- 11 months (deflazacort vs. placebo group, P < 0.05) [corrected]. Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group. Side effects were mild, consisting of moderate weight gain and slight behavioral changes.

Approaching a New Age in Duchenne Muscular Dystrophy Treatment

“…Deflazacort has been shown to prolong functional abilities with fewer side effects than prednisone. 14,15 A double-blinded, randomized trial comparing daily doses of 0.9 mg/kg of deflazacort to 0.75 mg/kg of prednisone or placebo showed no statistically significant differences in the two treatment groups in strength or function. 16 There is currently insufficient data on the long-term strength benefits and relative side effects of these various glucocorticosteroid regimes.…”

Review of Phase II and Phase III clinical trials for Duchenne muscular dystrophy

“…The first clinical trial in DMD demonstrating efficacy of prednisone occurred in 1974 [30]. Numerous trials that followed have looked for optimal age of initiation, dose and frequency [6][7][8][9][10][11][12]31]. Conclusions, to date, are that prednisone 0.75 mg/kg/day and deflazacort 0.9 mg/kg are equally effective in improving muscle strength and function in the short term (6 months to 2 years), and that prednisone 0.75 mg/kg/day is optimal compared to other class I dosing studies (1.5, 0.3 mg/kg/day and 0.75 mg/kg/q.…”

“…o.d. and 10 mg/kg/week) [6][7][8][9][10][11][12]31]. In these short-term treatment trials, adverse effects (weight gain, cushingoid appearance) were similar between studies.…”

“…Current evidencebased therapeutic interventions are limited to corticosteroids. Randomized controlled trials with prednisone or deflazacort, 6 --24 months in duration, have improved strength and function in boys with DMD [4][5][6][7][8][9][10][11][12]. Non-randomized follow-up studies of patients receiving these two treatments have shown sustained benefits from 5 to 15 years [13][14][15][16][17].…”

Prednisone 10 days on/10 days off in patients with Duchenne muscular dystrophy

“…This conclusion was based on trials using daily doses of corticosteroids, which proved to be superior to placebo [3,4] and to prednisone on an alternate-day scheme (1 day on/ 1 day off) [5]. Different doses as well as different intermittent schemes of administration have been tried in clinical trials with the aim of reducing side effects [6][7][8][9][10]. However, there is as yet no internationally accepted consensus on which corticosteroid treatment scheme is the best for patients with DMD.…”