Recent phase 3 randomised controlled trials of amyloid-targeting monoclonal antibodies in people with pre-clinical or early Alzheimer disease have reported positive results, raising hope of finally having disease-modifying drugs. Given their far-reaching implications for clinical practice, the methods and findings of these trials, and the disease causation theory underpinning the mechanism of drug action, need to be critically appraised. Key considerations are the representativeness of trial populations; balance of prognostic factors at baseline; psychometric properties and minimal clinically important differences of the primary efficacy outcome measures; level of study fidelity; consistency of subgroup analyses; replication of findings in similar trials; sponsor role and potential conflicts of interest; consistency of results with disease causation theory; cost and resource estimates; and alternative prevention and treatment strategies. In this commentary, we show shortcomings in each of these areas and conclude that monoclonal antibody treatment for early Alzheimer disease is lacking high-quality evidence of clinically meaningful impacts at an affordable cost.

中文翻译：

---

用于治疗早期阿尔茨海默病的单克隆抗体——对最近“积极”试验的评论

最近针对临床前或早期阿尔茨海默病患者进行的针对淀粉样蛋白的单克隆抗体的 3 期随机对照试验报告了积极的结果，这增加了最终获得缓解疾病药物的希望。鉴于其对临床实践的深远影响，这些试验的方法和结果，以及支撑药物作用机制的疾病因果理论，需要进行严格评估。关键考虑因素是试验人群的代表性；基线时预后因素的平衡；主要疗效结果指标的心理测量特性和最小的临床重要差异；研究保真度水平；亚组分析的一致性；重复类似试验的结果；发起人的角色和潜在的利益冲突；结果与疾病因果理论的一致性；成本和资源估算；以及替代预防和治疗策略。在这篇评论中，我们展示了这些领域中每个领域的缺点，并得出结论，早期阿尔茨海默病的单克隆抗体治疗缺乏以可承受的成本产生具有临床意义的影响的高质量证据。