187PPredicting long-term trajectories of performance of upper limb 2.0 (PUL) score in patients with Duchenne muscular dystrophy (DMD) via remote analytical collaboration

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-09-01 DOI:10.1016/j.nmd.2025.105540

M. Michaëls , J. Freimark , E. Billmyer , R. Hoek , Y. Krom , E. Fleerakkers , M. van der Holst , K. Helleman , P. van Weperen , C. Straathof , J. Marden , Z. Chen , W. Zhang , J. Signorovitch , S. Ward , E. Niks

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引用次数: 0

Abstract

PUL 2.0 is a key functional measure for assessing disease progression in DMD, especially after loss of ambulation, and has been used as an outcome in clinical trials. Predictive models for PUL trajectories can be used to contextualize trial outcomes, especially when there are no placebo controls. Additionally, understanding which patient characteristics are predictive of future changes in PUL can help inform clinical trial design. We developed a multivariable prognostic model for multi-year changes in PUL based on single-center real-world data (RWD) from patients with DMD. PUL data was modelled at site with RWD as input and without the need for sharing RWD. Change in PUL total score (ΔPUL) was modeled over time as a function of baseline age, PUL, and ambulatory status. Baseline was defined as the first visit with PUL entry item score of 1-5. Predictive performance was evaluated using 5-fold cross-validation (5-CV). Sixty-nine patients were included with a mean age of 14.3y (SD 5.9) at baseline, of which 52 (75.4%) were non-ambulant. At baseline, mean PUL was 25.9 (SD 11.1) and 37 patients (53.6%) had a PUL entry item score of 5, while 3 (4.4%), 10 (14.5%), 4 (5.8%) and 15 patients (21.7%) had an entry item score of 4, 3, 2, and 1, respectively. Annualized ΔPUL was -1.07 and the average patient had 3.5 PUL assessments post-baseline spanning a mean of 3.7 years of follow-up. The model including baseline age explained 55% of variation in ΔPUL with mean 5-CV prediction errors of ±4.5 overall and ±3.2, 4.3, 4.0 and 5.8 units at 1, 2, 3 and 4 years, respectively. A model excluding baseline age explained 52% of variation in ΔPUL. In both models, baseline PUL and ambulatory status were significant predictors of long-term ΔPUL trajectories. The use of widely available baseline characteristics to predict multi-year ΔPUL supports the potential for broad application of these models. Further validation is warranted to assess generalizability and additional prognostic factors.

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187 .通过远程分析协作预测杜氏肌营养不良（DMD）患者上肢2.0 （PUL）评分的长期表现轨迹

PUL 2.0是评估DMD疾病进展的关键功能指标，特别是在失去行动能力后，并已被用作临床试验的结果。PUL轨迹的预测模型可用于将试验结果背景化，特别是在没有安慰剂对照的情况下。此外，了解哪些患者特征可以预测PUL的未来变化，有助于为临床试验设计提供信息。基于DMD患者的单中心真实世界数据（RWD），我们建立了PUL多年变化的多变量预后模型。PUL数据在现场建模，RWD作为输入，不需要共享RWD。PUL总分（ΔPUL）随时间的变化作为基线年龄、PUL和活动状态的函数进行建模。基线定义为PUL条目得分为1-5的第一次就诊。采用5倍交叉验证（5-CV）评估预测性能。纳入69例患者，基线时平均年龄为14.3岁（SD 5.9），其中52例（75.4%）不能走动。基线时，平均PUL为25.9 (SD 11.1)， 37例（53.6%）患者PUL入项评分为5，而3例（4.4%）、10例（14.5%）、4例（5.8%）和15例（21.7%）患者PUL入项评分分别为4、3、2和1。年化ΔPUL为-1.07，平均患者基线后进行3.5次PUL评估，平均随访3.7年。包含基线年龄的模型解释了ΔPUL中55%的变异，平均5-CV预测误差为总体±4.5,1、2、3和4年时分别为±3.2、4.3、4.0和5.8个单位。排除基线年龄的模型解释了ΔPUL中52%的变异。在这两个模型中，基线PUL和运动状态是长期ΔPUL轨迹的重要预测因子。利用广泛可用的基线特征来预测多年期ΔPUL支持了这些模型广泛应用的潜力。进一步的验证是必要的，以评估普遍性和其他预后因素。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.