Associations Between Steroid Treatment and Clinical Outcomes Among Non-ambulatory Patients with Duchenne Muscular Dystrophy (DMD) (P1-1.Virtual)

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.

Conclusions: Steroid use after loss of ambulation was associated with delayed progression of important pulmonary, cardiac and functional deficits in DMD.

Disclosure: Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Capricor Therapeutics. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Catabasis. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epirium Bio. Dr. McDonald has received personal compensation in the range of $0-$499 for serving as a Consultant for Italfarmaco. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Santhera Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Astellas. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Catabasis. The institution of Dr. McDonald has received research support from Epirium Bio. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from Pfizer. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from NIDILRR. The institution of Dr. McDonald has received research support from Department of Defense. The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH. Oscar Mayer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Santhera. Oscar Mayer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Solid Biodcience. Oscar Mayer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Capricor. Oscar Mayer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fibrogen. Dr. Hor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capricor. Dr. Hor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stealth Therapeutics. Dr. Hor has received personal compensation in the range of $0-$499 for serving as a Consultant for Vertex. Dr. Hor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Diachi-Sankyo. Dr. Hor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catabasis. Dr. Hor has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronics Inc. Dr. Hor has received personal compensation in the range of $0-$499 for serving as a Consultant for PTC Therapeutics. Dr. Hor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Hor has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Fibrogen. The institution of Jessica Marden has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Analysis Group, Inc.. The institution of Jessica Marden has received research support from PTC Therapeutics. The institution of Jonathan Freimark has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Analysis Group, Inc. The institution of Henry Lane has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Analysis Group. Ms. Zhang has received personal compensation for serving as an employee of Analysis Group. Claudio Santos has received personal compensation for serving as an employee of PTC. Claudio Santos has received stock or an ownership interest from PTC. Dr. Able has received stock or an ownership interest from PTC Therapeutis. Dr. Able has received personal compensation in the range of $0-$499 for serving as a Employee with PTC therapeutics. The institution of James Signorovitch has received research support from PTC Therapeutics.