Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease
Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease
复制标题
评估阿尔茨海默病抗淀粉样蛋白免疫疗法的关键问题
DOI：
10.1093/braincomms/fcad175
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发表时间：
2023
影响因子：
4.8
通讯作者：
Liu K
中科院分区：
文献类型：
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作者：
Liu K
抗淀粉样蛋白免疫疗法是一类治疗阿尔茨海默病的新药，其临床益处是基于其通过降低脑淀粉样蛋白水平来改变病程的能力。在撰写本文时，两种降低淀粉样蛋白的抗体aducanumab和lecanemab已获得美国食品和药物管理局的加速批准，这类药物已进入阿尔茨海默病治疗管道。根据迄今为止有限的已发表临床试验数据，监管机构、付款人和医生将需要评估其疗效、临床有效性和安全性，以及成本和可及性。我们建议关注与治疗疗效、临床有效性和安全性相关的三个重要问题，以指导对这类重要药物的循证考虑。这些问题是：（1）试验统计分析是否适当，它们是否令人信服地支持疗效声明？(2)报告的治疗效果是否超过安全性问题，它们是否可推广到阿尔茨海默病患者的代表性临床人群？以及（3）数据是否令人信服地证明了病程的改变，表明在试验持续时间之外可能增加临床获益？我们提出了具体的方法来解释这些药物的试验结果，并强调了重要的不确定性领域，在这些领域需要额外的数据和对现有结果的谨慎解释。全世界数百万患者及其护理人员热切期待着阿尔茨海默病的安全，有效和可获得的治疗方法。虽然淀粉样蛋白靶向免疫疗法可能是有前途的疾病修饰阿尔茨海默病治疗方法，但对临床试验数据进行严格和无偏见的评估对于监管决策以及随后确定其在常规临床实践中的提供和效用至关重要。我们的建议为监管机构、付款人、医生和患者对这些药物进行循证评估提供了一个框架。
The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer’s disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer’s disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer’s disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer’s disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer’s disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.