Background: Psychiatric adverse effects during systemic corticosteroid therapy are common and well documented.
Objective: To report the frequency of behavioral problems in the phase 2b VISION-DMD study (NCT03439670) using the PARS III scale, a validated index of youth psychosocial adjustment in Duchenne muscular dystrophy (DMD), that consists of 28 items in 6 subscales (peer relations, dependency, hostility, productivity, anxiety/depression and withdrawal).
Methods: Patients (N=118) were randomized to placebo (n=29), prednisone 0.75 mg/kg/day (n=31), or vamorolone at 2 (n=30) or 6 (n=28) mg/kg/day. PARS III subscales assessed by parents were normalized as z-scores using historical data. Clinically relevant worsening in PARS III subscales was defined as a shift from normal baseline adjustment score (z-score <1) to an abnormal score (z-score ≥1) at week 24. Results: Moderate or severe behavioral adverse events (BAEs) were more frequent in the prednisone group (22.6%) than in any other arm (≤3.4% in all other groups). One patient on prednisone discontinued due to a severe BAE. Vamorolone showed no moderate or severe clinically relevant BAEs. After 24 weeks, the probability of having experienced at least 1 BAE was lowest in the placebo group, followed by vamorolone 2 mg/kg/day, vamorolone 6 mg/kg/day, and prednisone. Clinical worsening in hostility was more frequent with prednisone (26.1%) than vamorolone 6 mg/kg/day (15.4%), 2 mg/kg/day (9.1%), or placebo (8.0%). Clinical worsening in dependency and productivity was reported in >20% of patients with prednisone (24.0% and 26.9%, respectively) compared with <10% in any other group. Conclusion: Vamorolone 6 mg/kg/day was associated with an increase in mainly mild BAEs compared with placebo, but with a lower frequency and severity of BAEs reported compared with prednisone. PARS III subscales showed a reduced risk for psychosocial adjustment/functioning in hostility, dependency, and productivity with vamorolone compared with prednisone.