Associations between steroid treatment and clinical outcomes among non-ambulatory patients with Duchenne Muscular Dystrophy (DMD)

Other
95
Oscar Mayer, MD, Children’s Hospital of Philadelphia
Craig McDonald, MD, UC Davis Health
Kan Hor, MD, Nationwide Children's Hospital and The Ohio State University
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.
Jonathan Freimark, MPA, Analysis Group, Inc.
Henry Lane, BA, Analysis Group, Inc.
Adina Zhang, MSc
Molly Frean, PhD

OBJECTIVE: To compare outcomes by steroid treatment among non-ambulatory DMD patients. BACKGROUND: Corticosteroids are the standard of care for DMD; however, steroid use varies after loss of ambulation. Additional evidence on the clinical impact of different steroids is needed in this population. DESIGN/METHODS: A cohort of non-ambulatory DMD patients was identified from PRO-DMD-01: a prospective, observational study of DMD disease progression. Associations between steroid treatment (prednisone, deflazacort, or no steroids) and pulmonary, cardiac, and functional outcomes were assessed, including changes in forced vital capacity [FVC] %-predicted, left ventricular ejection fraction [LVEF], performance of upper limb [PUL] score, and loss of hand-to-mouth function. Outcomes were assessed using Kaplan-Meier analyses and Cox proportional hazards models for milestones, and mixed models with repeated measures for longitudinal outcomes. Models adjusted for selected baseline characteristics (e.g., age, steroid duration). RESULTS: 86 non-ambulatory patients (mean age 13.4 years; n=40 deflazacort; n=29 prednisone; n=17 no steroids) were included. Relative to no steroids, both steroids were associated with delays in median age at FVC %-predicted<60% (+0.9 [prednisone]; +2.3 [deflazacort]; log-rank p<0.01). Median ages at LVEF<55% were numerically prolonged, but non-significant (+2.7 [prednisone]; +0.8 [deflazacort]; p=0.65). While median ages at loss of hand-to-mouth function were not consistently reached, higher proportions of steroid patients maintained function at age 15 (85%-deflazacort; 83%-prednisone; 78%-no steroids; p<0.001). In adjusted Cox models, both steroids showed a significant delay in all three milestones relative to no steroids. In longitudinal models for change in PUL, prednisone patients had significantly slower decline compared to no steroids (+2.5 points/year; p=0.03), and deflazacort patients were significantly slower than prednisone (+1.5 points/year; p=0.04). Changes in FVC %-predicted and LVEF indicated significantly slower decline for both steroids relative to none. CONCLUSION: Steroid use after loss of ambulation was associated with delayed progression of important pulmonary, cardiac and functional deficits in DMD.