Background: Corticosteroids are recommended as standard of care for patients with Duchenne muscular dystrophy (DMD). However, children with DMD are on average shorter than the general population by the age of 5 years, and daily dosing with prednisone or deflazacort leads to further stunting of growth (Bello et al. 2015 PMID: 26311750; Stimpson et al. 2022 PMID: 35073949). In the Phase 2b VISION-DMD study (NCT03439670) height percentile (adjusted by age using US CDC growth charts) was shown to decline from baseline to month 6 in patients treated with prednisone, but not in those treated with the dissociative corticosteroid vamorolone at 6 mg/kg/day (Guglieri et al. 2022 PMID: 36036925).
Objective: To further study the impact of vamorolone or prednisone vs placebo on linear growth in the VISION-DMD study by reporting unadjusted changes in height (cm) and patient-level changes in height over the course of 6 months.
Methods: The design of the VISION-DMD study has been reported previously. Boys aged 4 to <7 years were randomised to placebo, prednisone 0.75 mg/kg/day, vamorolone 2 mg/kg/day or vamorolone 6 mg/kg/day. Height was recorded at baseline and at 12-week intervals. This analysis included 118 participants in the safety population. Results: At baseline, median height ranged from 106 to 111 cm across the treatment groups. After 6 months of treatment, median height increases were lower in the prednisone group (n=30, 2.60 cm) than in the placebo group (n=28, 3.55 cm, p=0.03) or vamorolone 6 mg/kg/day group (n=26, 3.50 cm, p=0.009). There were no significant differences in median height increase between either vamorolone group and placebo (p>0.1). In the prednisone group, 30.0% of children showed reductions in height z-score ≥0.2 standard deviations after 6 months, compared with 18.5% in the vamorolone 2 mg/kg/day group, 10.7% in the placebo group and 0 children in the vamorolone 6 mg/kg/day group.
Conclusion: In patients with DMD aged 4 to <7 years, absolute height (cm) values after 6 months of treatment showed similar increases with vamorolone and placebo, while significantly less growth (i.e. growth stunting) was observed with prednisone.