24-week open label clinical trial to test safety and efficacy of oral weekly prednisone in adults with Becker (BMD) and Limb-Girdle Muscular Dystrophy (LGMD).
Aaron S. Zelikovich1, Benjamin C. Joslin2, Elizabeth M. McNally3, Senda Ajroud-Driss2
1New York Presbyterian/ Weill Cornell Medicine, 2Northwestern University Feinberg School of Medicine - Department of Neurology, 3Northwestern University - Center for Genetic Medicine
Objective:
To determine if once weekly prednisone is safe and can benefit patients with BMD and LGMD.
Background:
Corticosteroids improve mortality and ambulation in patients with Duchenne Muscular Dystrophy (DMD). High-dose, weekend steroids in DMD provides similar benefits with fewer adverse effects as compared to daily steroids. Animal models of LGMD treated with once-weekly steroids have previously shown to promote strength and lean muscle mass. We now conducted an open label safety and tolerability trial of weekly steroids in BMD and LGMD (NCT04054375).
Design/Methods:
Participants received prednisone at 0.75-1g/kg orally on Mondays after dinner for twenty-four weeks. Participants completed functional assessments, serum chemistry and lipid profiles, whole body DEXA scans, and muscle MRI imaging at baseline and end of study.
Results:
Twenty patients completed 24-weeks of once-weekly prednisone (1 BMD, 19 LGMD; 13 males, 7 females; ages 18-63 years old). Both ambulatory and non-ambulatory patients were enrolled to represent the entire disease spectrum. There was no significant negative impact on body weight, blood pressure, forced vital capacity, bone density or serum chemistries/lipids. Serum CK significantly decreased and was accompanied by an increase in lean muscle mass measured by whole body DEXA scans. Ambulatory patients (n=6) experienced a trend toward improvement in 6-minute walk distance and time to run 10 meters. Once-weekly prednisone was overall well tolerated with the most frequent side effects being increased anxiety on Monday nights and facial acne. All but one participant chose to continue to take weekly steroids after completing the study.
Conclusions:
Once weekly steroids, given as 0.75-1gm/Kg was well tolerated in BMD and LGMD. Additional multicenter randomized clinical trials are needed to better understand how weekly steroids may benefit patients with BMD and LGMD.