OBJECTIVES: The natural history of disease progression in Duchenne muscular dystrophy (DMD) has been categorized into eight health states based on the input from clinicians, patients, and caregivers by Project HERCULES. The current study uses natural history data to further characterize patients with DMD by health state.

METHODS: Patients from nine data sources (five clinical trial placebo arms, one real-world data and three natural history data) were categorized into eight health states based on the model reported by Project HERCULES: two ambulatory states, one transfer state, and five non-ambulatory states. State definitions were modified and verified, with clinical input, to account for data availability. Demographic and functional measures were characterized within each health state.

RESULTS: The study included 1,175 patients across 5,296 visits (4,989 ambulatory and 307 non-ambulatory visits). Patients were predominantly white and not Hispanic or Latino. Within each health state, substantial variation was observed for each functional measure assessed, but on average, patients were older and exhibited worse ambulatory function, pulmonary capacity, upper limb function and cardiac function for each subsequent health state. North Star Ambulatory Assessment (NSAA) total score was 23.7 (IQR 20-30) for early ambulatory patients, 12.7 (IQR 9-16) for the late ambulatory, and 3.8 (IQR 2.8-5) for transfer patients. Spirometry as measured by FVC%-predicted was 93.0±0.7 for ambulatory and transfer patients and was 77.2±1.7, 69.3±4.6, 42.3±1.2, 39.2±1.3, and 20.6±1.6 for the five respective non-ambulatory health states. Until the last health state (requiring full ventilation), over approximately 80% of patients were on steroids (either deflazacort or prednisone), with approximately 70% of patient visits using them daily.

CONCLUSIONS: Health states proposed for DMD disease progression showed concordantly worsened function for later health states across different domains, including ambulatory, pulmonary, upper-limb and cardiac function. These findings further characterize health states and their interpretation in economic modeling and decision-making.