FP.26 Early effect of corticosteroids on functional outcomes in young patients with Duchenne muscular dystrophy within the first 18 months of treatment

Abstract

Glucocorticoids (GC) are part of the standard of care in Duchenne muscular dystrophy (DMD). The early effect of GC on motor function outcomes (FO) remains to be characterized. This study describes motor FO at the time of starting GC and identify factors that influence FO trajectories. FO data from the first 18 months of the FOR-DMD study were analysed. In total, 196 GC-naïve boys, age 4 - <8 years were randomized to receive daily prednisone (0.75 mg/kg), daily deflazacort (0.9 mg/kg), or intermittent prednisone (0.75 mg/kg 10 days on/10 days off) and assessed on the rise from floor velocity (TRF-vel), 10-meter walk/run velocity (10MWR-vel), North Star Ambulatory Assessment (NSAA) total score and the 6-minute walking test distance (6MWT) at baseline, 3-, 6-, 12- and 18 months. A linear mixed model was performed; fixed effects included: age at baseline, GC regime, mutation type; baseline height and dichotomized baseline FO cut-off values. Age group distribution was 20% (n=40) 4 – 4.9 y, 40% (n=78) 5 – 5.9 y, 24% (n=47) 6 – 6.9 y, and 16% (n=31) 7 – 7.9 y. 65 boys were allocated to daily prednisone and daily deflazacort respectively and 66 to intermittent prednisone. Distribution by baseline dichotomized FO cut-off values: 60% (n=118) boys had a 6MWT > 330 m; 73% (n=143) TRF-vel > 0.138 /second; 69% (n=136) 10MWR-vel > 0.142 /second and 42% (n=83) NSAA > 22 points. Boys in the 7 – 7.9 y age group at baseline showed lower performances in all the FO up to 18 months compared to boys in the 5 – 5.9 y group. Boys on intermittent prednisone had lower trajectories in the TRF-vel, 10MWR-vel, 6MWT compared to daily prednisone. Boys with a baseline FO below the cut-off values showed lower trajectories than boys above them. Mutation type had no effect on FO at 18-months. Understanding the early effect of GC on motor FO can be useful to evaluate the effect of novel therapies and inform clinical trial design in DMD.