Dose Dependent Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review and Meta Analysis of Randomized Controlled Trials

Background: Duchenne muscular dystrophy (DMD) is a severe inherited neuromuscular disorder causing progressive muscle weakness in boys. Corticosteroids are standard therapy but have significant long-term adverse effects. Vamorolone, a dissociative steroid, may preserve efficacy while reducing toxicity. This systematic review and meta-analysis evaluated whether higher doses improve motor outcomes while maintaining safety in boys with DMD. Methods: A systematic search of PubMed, Web of Science, Embase, Scopus, and the Cochrane Library was conducted to identify randomized controlled trials comparing vamorolone at 2 mg/kg/day versus 6 mg/kg/day in boys with DMD. Primary motor outcomes included time to stand from supine (TTSTAND), six-minute walk distance (6-MWD), time to run or walk 10 meters (TTRW), and time to climb four stairs (TTCLIMB). Changes in BMI z score were assessed as a safety indicator. Data were analyzed using Review Manager (RevMan) 5.4 following PRISMA guidelines. Results: Three randomized controlled trials involving 118 boys met the inclusion criteria. The 6 mg/kg/day dose demonstrated significantly greater improvement in motor outcomes compared with the 2 mg/kg/day dose, including TTSTAND (MD = 0.04, 95% CI [0.02–0.07], p < 0.0001), 6-MWD (MD = 26.27, 95% CI [1.55–50.99], p = 0.04), TTRW (MD = 0.13, 95% CI [0.07–0.19], p < 0.0001), and TTCLIMB (MD = 0.04, 95% CI [0.01–0.07], p = 0.006). BMI z score changes were comparable between groups. Conclusion: Vamorolone 6 mg/kg/day improves motor function more than 2 mg/kg/day without increased safety concerns. Larger long-term trials are required to confirm these findings.