Associations Between Daily Deflazacort or Prednisone and Ages at Disease Progression Milestones Among Patients with Duchenne Muscular Dystrophy (DMD)



Poster Number: 110


Craig McDonald, MD, University of California Davis Health System, Sacramento, CA, USA, Claudio L. Santos, MD, MBA, PTC Therapeutics Inc., South Plainfield, NJ, USA, Rich Able, PhD, PTC Therapeutics, James Signorovitch, PhD, Analysis Group, Inc., Boston, MA, USA, Jessica Marden, ScD, Analysis Group, Inc., Molly Frean, PhD, Henry Lane, BA, Analysis Group, Inc., Adina Zhang, MSc, Ha Nguyen, BA

BACKGROUND/OBJECTIVE: Corticosteroids are the standard of care for treatment of DMD. This study compared ages at disease progression milestones between patients on daily regimens of prednisone and deflazacort.
METHODS: A cohort of DMD patients was identified from the PRO-DMD-01 and Cooperative International Neuromuscular Research Group (CINRG) natural history studies. Associations between daily steroid treatment (deflazacort or prednisone) and disease progression milestones representing progressive loss of ambulatory function were assessed using Kaplan-Meier analyses and Cox proportional hazards models adjusted for data source and age at steroid initiation. Milestones included timed rise from floor (RFF) >=5 seconds, RFF >=10 seconds, inability to RFF, inability to complete 4-stair climb (4SC), and loss of ambulation.
RESULTS: 463 patients (mean age 9.86 years; n=288 deflazacort; n=175 prednisone) were identified. At baseline, patients on deflazacort were slightly older (mean age 10.34 vs. 9.08 [prednisone]; p<0.01); however, dose and duration of steroid therapy as well as baseline functional status were similar between steroid groups. Relative to prednisone, deflazacort was associated with significant delays in median age at all progression milestones. Specifically, deflazacort patients experienced a delay in timed RFF >=10 seconds and RFF >=5 seconds of 0.88 years (log-rank p<0.01) and 0.94 years (p<0.05), respectively. Delays in progression were also observed for inability to RFF (+1.61 years, p<0.001) and inability to complete 4SC (+1.87 years; p < 0.01) for patients receiving deflazacort vs. prednisone. Median age at loss of ambulation was also older for deflazacort (15.92 vs. 14.89 years; p<0.001). In adjusted Cox models, hazard ratios favored deflazacort for all outcomes, but did not consistently reach statistical significance.
CONCLUSION: Use of daily deflazacort was associated with delayed progression of multiple ambulatory milestones in patients with DMD. This study adds to the evidence comparing outcomes across DMD patients on different steroid types using a longitudinal and geographically-diverse dataset.