P.59 - Long-term benefits of glucocorticoids in Duchenne muscular dystrophy: is it worth it?

Abstract

The CINRG Duchenne muscular dystrophy (DMD) Natural History Study (DNHS) examined the long-term benefits of glucocorticoids (GC) based on milestone-related disease progression across the lifespan and risk of death. The 10-year prospective DNHS followed 440 males ages 2–28 years with DMD comparing none or < 1 month and 3 1 year cumulative GC treatment with regard to progression to 8 disease-related and clinically meaningful mobility and upper limb milestones. Kaplan-Meier survival analyses compared GC treatment groups for time to stand from supine 3 5 and 3 10 seconds, and loss of: stand from supine, 4-stair climb, ambulation, full overhead reach, hand to mouth, and hand function. Risk of death was also assessed for those whose absolute FVC decreased to < 1 liter and GC use. There were significant delays in time to all events in subjects with 3 1 year GC treatment (Log-rank p-values < 0.001). GC treatment prolonged median age at loss of mobility milestones by 2.1 to 4.4 years and upper limb milestones by 2.8 to 8.0 years. Within GC-treated patients, deflazacort treatment prolonged median age at loss stand from supine by 2 years (p = 0.01), age at loss of ambulation by 2.5 years (p = 0.01), and age at loss of hand to mouth function by 2.6 years (p = 0.01) relative to prednisone use. Transitions across disease-progression milestones were significantly related to health-related quality of life measured by PODCI. Forty-five deaths occurred and the odds ratio for death for those on GC treatment 3 1 year showed a reduced death risk by over 50% (odds ratio 0.47, 95% CI 0.22–1.00, p = 0.05). In patients with DMD, GC treatment reduces risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan and reduces risk of death.