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. 2024 Oct 30;19(10):e0307118.
doi: 10.1371/journal.pone.0307118. eCollection 2024.

Characterization of patients with Duchenne muscular dystrophy across previously developed health states

Francesco Muntoni  1 , Nathalie Goemans  2 , Nate Posner  3 , James Signorovitch  4   5 , Michaela Johnson  4 , Chujun He  4 , Patricia Dorling  6 , Katherine Beaverson  3 , Jose Alvir  3 , Matthias Mahn  3 , Susan J Ward  5 , Craig M McDonald  7 , Eugenio Mercuri  8   9 ; PRO-DMD-01 study, the Imaging DMD study, iMDEX, the collaborative Trajectory Analysis Project (cTAP)
Affiliations

Characterization of patients with Duchenne muscular dystrophy across previously developed health states

Francesco Muntoni et al. PLoS One. .

Abstract

Project HERCULES has developed a natural history model (NHM) of disease progression in Duchenne muscular dystrophy (DMD) that comprises eight ordered health states (two ambulatory states, one transfer state indicating increased caregiver burden in which patients cannot walk/run 10m or rise from floor but can still support their own weight, and five non-ambulatory states). The current study used data from nine sources (clinical trial placebo arms, one real-world dataset, and three natural history datasets) to further characterize patients with DMD according to these health states. The study included 1,173 patients across 5,306‬ visits. Patients were on average older and exhibited worse ambulatory, pulmonary, upper limb, and cardiac functions with each successive health state. Mean±SE ages increased monotonically across health states, starting with 8.47±0.07 for early ambulatory, 10.86±0.13 for late ambulatory, 11.65±0.35 for transfer state, and ranging from 13.17±0.32 to 16.84±0.37 for the non-ambulatory states. North Star Ambulatory Assessment (NSAA) total score, which measures motor function and ranges from 34 (best) to 0 (worst), was 23.7 (interquartile range [IQR]: 20-30) for early ambulatory patients, 12.7 (IQR: 9-16) for late ambulatory patients, and 3.9 (IQR: 2-5) for transfer patients. Pulmonary function as measured by mean±SE of forced vital capacity percent predicted (FVC%p) was 94.5±0.8 for early ambulatory, 89.1±1.4 for late ambulatory, and 80.2±2.8 for transfer states, and decreased from 77.2±1.7 to 20.6±1.6 across the five non-ambulatory health states. In summary, these findings further characterize health states and their interpretation in economic modeling and decision-making in DMD management.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: FM is a member of the Rare Disease Scientific Advisory Group for Pfizer and of Dyne Therapeutics SAB and has participated in SAB meetings for PTC, Sarepta, Pfizer, Roche, Santhera, and Wave Therapeutics. UCL and Great Ormond Street Hospital have received funding from Pfizer, Italfarmaco, Wave, Santhera, Roche, NF Pharma, ReveraGen, Genethon, and Sarepta regarding clinical trials. NG has received compensation for consultancy services from Eli Lilly, Italfarmaco, PTC Therapeutics, BioMarin Pharmaceutical, Pfizer, Avidity, Daiichi Sankyo, Wave, and Santhera and has served as site investigator for GlaxoSmithKline, Prosensa, BioMarin Pharmaceutical, Italfarmaco, Eli Lilly, Wave, and Sarepta. NP and JA are employees of Pfizer Inc. and own stock/stock options. JS cofounded the cTAP and is an employee of Analysis Group, Inc., a consulting firm that received funding from the membership of cTAP to conduct this study. MJ is an employee of Analysis Group, Inc., a consulting firm that received funding from the membership of cTAP to conduct this study. SJW cofounded and manages cTAP and has received funding from the membership of cTAP to facilitate this study. CMM has served as a consultant for PTC Therapeutics, BioMarin Pharmaceutical, Sarepta Therapeutics, Eli Lilly, Pfizer Inc., Santhera Pharmaceuticals, Cardero Therapeutics, Inc., Catabasis Pharmaceuticals, Capricor Therapeutics, Astellas Pharma (Mitobridge), and FibroGen, Inc.; serves on external advisory boards related to DMD for PTC Therapeutics, Sarepta Therapeutics, Santhera Pharmaceuticals, and Capricor Therapeutics; and reports grants from the US Department of Education/National Institute on Disability and Rehabilitation Research, National Institute on Disability, Independent Living, and Rehabilitation Research, US NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH/National Institute of Neurologic Disorders and Stroke, US Department of Defense, and Parent Project Muscular Dystrophy US. EM has served on clinical steering committees and/or as a consultant for Eli Lilly, Italfarmaco, PTC Therapeutics, Sarepta, Santhera, and Pfizer; has served as PI for GlaxoSmithKline, Prosensa, BioMarin Pharmaceutical, Italfarmaco, Roche, PTC, Pfizer, Sarepta, Santhera, Wave, NS Pharma, and Eli Lilly. PD, KB, and MM were Pfizer Inc. employees at the time the study was conducted. CH was an Analysis Group, Inc. employee at the time the study was conducted. This does not alter our adherence to PLoS One policies on sharing data and materials.

Figures

Fig 1
Fig 1. Definition of health states.
Abbreviations: FVC%p, forced vital capacity percent predicted; HTMF, hand-to-mouth function; NSAA, North Star Ambulatory Assessment; PUL, Performance of Upper Limb.
Fig 2
Fig 2
Distributions of patient ages (A) and levels of pulmonary function (B) across health states. Abbreviations: FVC, forced vital capacity; HTMF, hand-to-mouth function.
Fig 3
Fig 3. Steroid use across health states.
Percents are based on the visits in each respective health state. Abbreviations: HTMF, hand-to-mouth function.
Fig 4
Fig 4. Left ventricular ejection fraction across health states.
Sample sizes and patient counts reported per health state represent observations with available data for left ventricular ejection fraction. Percentiles are based on the visits in each respective health state. Abbreviations: HTMF, hand-to-mouth function.
See this image and copyright information in PMC

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