Deflazacort treats muscular dystrophy: increasing muscle strength

Deflazacort treats muscular dystrophy and increases muscle strength

Efficacy in treating Duchenne muscular dystrophy (DMD) was demonstrated in Study 1, a 52-week multicenter, randomized, double-blind, placebo-controlled study conducted in the United States and Canada. The study population included 196 male pediatric patients aged 5 to 15 years with documented dystrophin gene mutations, onset of frailty before age 5 years, and serum creatinine kinase activity at least 10 times the upper limit of normal (ULN).

Patients were randomized to receive (0.9 or 1.2 mg/kg/day), active comparator, or placebo. Comparison with placebo after 12 weeks of treatment. After 12 weeks, placebo patients were rerandomized to receive deflazacort or active control; all patients continued treatment for 40 weeks. Baseline characteristics were comparable between treatment groups.

In Study 1, efficacy was assessed by assessing changes in mean strength across 18 muscle groups between baseline and week 12. Individual muscle strength is graded using the modified Medical Research Council (MRC) 11-point scale, with higher scores indicating greater strength.

The change in mean muscle strength score between baseline and week 12 was significantly greater in the deflazacort 0.9 mg/kg/day group than in the placebo group (deflazacort 0.15 vs placebo -0.10).

Deflazacort treats muscular dystrophy and slows progression of disability

Disease progression over 48 weeks in boys treated with deflazacort and prednisone/prednisolone versus placebo was described in two recent Duchenne muscular dystrophy (DMD) clinical trials.

The trial included ambulatory boys with DMD who received placebo in the Phase 3 trials of ataluren (n=115) and tadalafil (n=116). These trials required at least 6 months of corticosteroid use and stable baseline dosage. Mixed models were used to estimate the association between corticosteroid use and dynamic functional changes at 48 weeks. Adjusted differences between corticosteroid groups were summarized in a meta-analysis.

Results: In the meta-analysis, deflazacort-treated patients versus prednisolone/prednisolone-treated patients experienced a mean 6-minute walk distance of 28.3 m; supine ascent of 2.9 sec; 4-step climb of 2.3 sec; and a Polaris Dynamic Assessment linear score of 2.9. Conclusions: Patients treated with deflazacort experienced significantly reduced decline in physical function over 48 weeks.

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References

McDonald CM, Sajeev G, Yao Z, McDonnell E, Elfring G, Souza M, Peltz SW, Darras BT, Shieh PB, Cox DA, Landry J, Signorovitch J; ACT DMD Study Group and the Tadalafil DMD Study Group. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A meta-analysis of disease progression rates in recent multicenter clinical trials. Muscle Nerve. 2020 Jan;61(1):26-35. doi: 10.1002/mus.26736. Epub 2019 Nov 7. PMID: 31599456; PMCID: PMC6973289.