Dubowitz Neuromuscular Centre, Great Ormond Street Institute of Child Health, London, United Kingdom.
University Hospitals Leuven, Child Neurology, Leuven, Belgium.
PLoS One. 2024 Oct 30;19(10):e0307118. doi: 10.1371/journal.pone.0307118. eCollection 2024.
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.
HERCULES 项目开发了一种杜氏肌营养不良症（DMD）疾病进展的自然史模型（NHM），该模型包含八个有序的健康状态（两个可移动状态，一个转移状态表示照顾者负担增加，患者无法行走/跑步 10m 或从地板上站起来，但仍能支撑自己的体重，以及五个非可移动状态）。本研究使用了来自九个来源的数据（临床试验安慰剂组、一个真实世界数据集和三个自然史数据集），根据这些健康状态进一步描述 DMD 患者。该研究共纳入了 1173 名患者，共 5306 次就诊。随着健康状态的依次进展，患者的平均年龄更高，表现出更差的移动、肺部、上肢和心脏功能。健康状态的平均年龄呈单调递增，从早期可移动状态的 8.47±0.07 岁、晚期可移动状态的 10.86±0.13 岁、转移状态的 11.65±0.35 岁，到非可移动状态的 13.17±0.32 岁到 16.84±0.37 岁不等。北星可移动评估（NSAA）总评分，用于测量运动功能，范围从 34（最佳）到 0（最差），早期可移动患者为 23.7（四分位距 [IQR]：20-30），晚期可移动患者为 12.7（IQR：9-16），转移患者为 3.9（IQR：2-5）。肺活量作为用力肺活量占预计值的百分比（FVC%p）的平均值±标准差测量，早期可移动状态为 94.5±0.8，晚期可移动状态为 89.1±1.4，转移状态为 80.2±2.8，从五个非可移动健康状态逐渐下降到 77.2±1.7 到 20.6±1.6。总之，这些发现进一步描述了健康状态及其在 DMD 管理的经济建模和决策中的解释。
