Date of Graduation
Master of Science in Physician Assistant Studies
Background: Duchenne muscular dystrophy (DMD) is a common X-linked neuromuscular disease that causes progressive muscle weakness and leads to early death. Those affected often present with muscle weakness as their primary symptom and generally develop scoliosis, respiratory, and cardiac complications as well. In the natural course of DMD, affected males lose ambulation at a mean age of 9.5 years and death generally ensues in the second or third decades of life. There is no curative treatment and corticosteroids are the only approved therapy for slowing the progression of the disease. While much research has been done assessing efficacy of corticosteroid treatment, there is still great uncertainty concerning the optimum dosing schedule.
Method: An extensive search of medical literature was conducted with Medline-OVID, CINAHL, Web of Science and MDConsult using key terms: Duchenne muscular dystrophy, corticosteroids or adrenal cortex hormones, and drug administration schedule or alternate. Studies that assessed efficacy of alternate-day dosing and intermittent dosing regimens were selected and compared to data collected on daily dosing regimens. Articles that met inclusion criteria were chosen and assessed for quality using the GRADE method.
Results: Four studies met inclusion criteria and were included in this systematic review. Two studies focused on alternate-day dosing regimens and two studies evaluated intermittent corticosteroid dosing schedules. While all regimens were found to prolong ambulation and slow progression of DMD when compared to the natural course of the disease, daily dosing seems to be most effective. Alternate-day and intermittent dosing schedules also prolong independent ambulation but not to the extent that daily corticosteroid therapy did. Lastly, significant scoliosis and declines in respiratory function were delayed in patients treated with all corticosteroid dosing regimens.
Conclusion: Corticosteroids have shown to slow progression of DMD by prolonging ambulation, postponing or preventing the development of scoliosis, and delaying respiratory function decline. Evidence suggests that daily corticosteroid therapy is most efficacious in managing DMD but with highest rates of moderate to severe side effects. A recommendation can be made for the use of alternate-day corticosteroid dosing initiated early in the disease process (age 2-4 years). More research is needed to determine whether or not alternative regimens can be as effective as daily treatment and at what age to initiate therapy.
Keywords: Duchenne muscular dystrophy, corticosteroids, dosing schedule, prolonging ambulation
Cooley, Jessica, "Optimal Dosing Schedule in the Treatment of Duchenne Muscular Dystrophy" (2014). School of Physician Assistant Studies. 484.