Defining and labeling disease-modifying treatments for Alzheimer's disease
Defining and labeling disease-modifying treatments for Alzheimer's disease
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DOI：
10.1016/j.jalz.2008.12.003
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发表时间：
2009-09-01
影响因子：
14
通讯作者：
Cummings, Jeffrey L.
中科院分区：
文献类型：
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作者：
Cummings, Jeffrey L.
阿尔茨海默病（AD）可以用对症疗法、神经保护疗法或神经恢复疗法来治疗。神经保护和神经恢复干预是改善疾病的疗法。疾病改善可以定义为影响疾病的基础病理生理学并对AD病程具有有益结果的治疗或干预。在临床试验中，通过证明对生物标志物（如磁共振成像（MRI）上的内侧颞叶萎缩或脑脊液中tau或磷酸化tau水平降低）的影响，可以支持影响疾病根本原因的标准。临床试验的主要临床结局的药物-安慰剂差异支持对AD临床病程有益的声明。生物标志物结果和临床试验结果之间的统计学显著相关性将支持这些结果基于相同的潜在机制的说法。延迟开始或交错停药设计本身可能支持疾病改善声明，但难以实施。临床结果和生物标志物测量的组合是一个更可能的途径，以改善疾病的索赔。疾病调节剂的标记可能是指疾病进展减缓、达到预定义疾病里程碑的延迟或生物标志物（如MRI显示的脑萎缩或心室扩大）进展减缓。预防声明将在很大程度上取决于生物标志物的结果。(C)2009年阿尔茨海默氏症协会。All rights reserved.
Alzheimer's disease (AD) might be treated with symptomatic, neuroprotective, or neurorestorative therapies. Neuroprotective and neurorestorative interventions are disease-modifying therapies. Disease modification can be defined as treatments or interventions that affect the underlying pathophysiology of the disease and have a beneficial outcome on the course of AD. In a clinical trial the criteria for affecting the underlying cause of the disease can be supported by demonstrating an effect on a biomarker such as medial temporal atrophy on magnetic resonance imaging (MRI) or diminished tau or phospho-tau levels in cerebrospinal fluid. The claim for a beneficial effect on the clinical course of AD is supported by a drug-placebo difference on the primary clinical outcomes of the clinical trial. A statistically significant correlation between the biomarker outcome and the clinical trial outcome would support the claim that these are based on the same underlying mechanism. Delayed start or staggered withdrawal designs might in themselves support a disease-modifying claim but are difficult to implement. A combination of clinical outcomes and biomarker measures is a more likely pathway to a disease-modifying claim. Labeling of disease-modifying agents might refer to slowing of disease progression, delay in reaching predefined disease milestones, or reduction in progression of a biomarker such as cerebral atrophy or ventricular enlargement on MRI. Prevention claims will depend heavily on biomarker outcomes. (C) 2009 The Alzheimer's Association. All rights reserved.