抗多巴胺能药物治疗和亨廷顿病的临床变化：因果分析

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-03-18 DOI:10.1002/mds.30164

Michal Geva PhD, Y. Paul Goldberg MBChB, PhD, Henk Schuring PharmD, Andrew M. Tan PhD, Jeffrey D. Long PhD, Michael R. Hayden MBChB, PhD

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引用次数: 0

摘要

背景：抗多巴胺能药物（ADM）常用于亨廷顿病（HD）的症状管理。过去的研究证据表明，ADMs与HD患者较差的临床结果相关，但其对各个领域的影响仍未得到充分探讨。目的：我们使用因果推理分析来了解ADM的使用对2年多领域HD临床进展指标的影响。方法：我们采用新用户设计的Enroll‐HD数据库，将首次就诊后开始使用ADM的队列与未接触ADM的队列进行比较。为了控制27个协变量，我们使用了双重稳健的目标最大似然估计，并进行了两次分析。首先，我们分析了ADM治疗基线后2年的12个结果指标。其次，我们检查了ADM剂量与临床结果的关系。结果与非ADM组相比，ADM暴露组在临床结果测量方面表现出更快的变化，后者在认知和功能结果测量以及综合统一亨廷顿病评定量表（cUHDRS）方面具有统计可靠性。运动域分析显示，与未接触ADM组相比，ADM暴露组运动迟缓的变化更快，但在chorea或总运动评分（TMS）方面没有差异。与非ADM组相比，较高ADM剂量也显示出更大的差异。结论sadm的使用与临床测量的快速变化有关，特别是在认知和功能领域。然而，建立ADM使用与疾病进展之间的因果关系的假设可能尚未完全满足，需要进一步的研究。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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Antidopaminergic Medications and Clinical Changes in Measures of Huntington's Disease: A Causal Analysis

Background

Antidopaminergic medications (ADM) are often used for symptom management of Huntington's disease (HD). Evidence from past research suggests that ADMs are associated with worse clinical outcomes in HD, but their impact on various domains remains underexplored.

Objective

We used causal inference analysis to understand the impact of ADM use on measures of clinical progression in HD across multiple domains over 2 years.

Methods

We used the Enroll-HD database with a new-user design, which compared a cohort that initiated ADM use after the first visit with an unexposed cohort that remained off ADMs. To control for 27 covariates, we used a doubly robust targeted maximum likelihood estimation and conducted two analyses. First, we analyzed ADM treatment 2 years post-baseline and separately for 12 outcome measures. Second, we examined the association of ADM dose with measures of clinical outcomes.

Results

The ADM-exposed group exhibited faster change in measures of clinical outcome compared with the off-ADM group, which was statistically reliable in cognitive and functional outcome measures, and the composite Unified Huntington's Disease Rating Scale (cUHDRS). Motor domain analyses showed faster change in bradykinesia in the ADM-exposed group versus off-ADM but no difference in chorea or total motor score (TMS). Higher ADM doses also showed greater differences compared to the off-ADM group.

Conclusions

ADM use was associated with more rapid change in clinical measures, particularly in cognitive and functional domains. However, assumptions required to establish causation between ADM use and disease progression may not have been fully met, and further research is warranted. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.