Importance Several anti-amyloid monoclonal antibodies have been developed for slowing the progression of Alzheimer disease (AD). Among the furthest developed are aducanumab, which received accelerated approval from the US Food and Drug Administration in 2021, and donanemab, which is currently undergoing phase 3 trials. The cost-effectiveness of these treatments has not been established. Objectives To estimate the cost-effectiveness of aducanumab and donanemab relative to standard care for early AD in the US. Design, Setting, and Participants A decision analytic model was used to estimate the lifetime health and economic outcomes of adults with early AD, from US healthcare sector and societal perspectives. Simulated patients had a mean (SD) age of 75.2 (5.5) years; 65% had mild cognitive impairment and 35% had mild dementia. Analyses were conducted from April 6, 2021, to January 20, 2022. Interventions Standard care, aducanumab (selected inputs including disease progression hazard ratio [HR] of 0.89 [95% CI, 0.63-1.15], annual price of $28 000, and twice-yearly monitoring with magnetic resonance imaging [MRI] of the brain), or donanemab (selected inputs including disease progression HR of 0.68 [95% CI, 0.44-0.99], annual price of $28 000, and twice-yearly monitoring with MRI of the brain and amyloid positron emission tomography [PET] monitoring). Donanemab was switched to placebo after substantial amyloid reduction on PET imaging, which occurred in 27% of patients at 6 months and 55% of patients at 12 months. Main Outcomes and Measures Quality-adjusted life-years (QALYs); costs, in 2020 US dollars; incremental cost-effectiveness ratios (ICERs); and value-based prices, defined as the maximum price at which a treatment would be cost-effective given a cost-effectiveness threshold of ICER of $150 000/QALY. Results Lifetime QALYs increased by 0.133 with aducanumab and 0.408 with donanemab. Total health care sector and societal costs increased by $130 100 and $127 800, respectively, with aducanumab and by $78 700 and $71 600, respectively, with donanemab, driven largely by drug costs ($119 000 for aducanumab and $44 600 for donanemab). Health care sector and societal ICERs relative to standard care were $981 000/QALY and $964 000/QALY, respectively, for aducanumab and $193 000/QALY and $176 000/QALY, respectively, for donanemab. In sensitivity analysis, aducanumab's value-based price remained less than $50 000/y, even when assuming a 90% reduction in disease progression. Donanemab's value-based price surpassed $50 000/y once its efficacy exceeded 50%. Conclusions and Relevance These findings suggest that at current expected prices, neither aducanumab nor donanemab would be cost-effective for early AD in the US. Donanemab's dosing scheme, in which patients suspend treatment on achieving substantial amyloid reductions, may provide a rubric by which sufficiently effective anti-amyloid antibody treatments could be cost-effective even when priced comparably to other biologics.

中文翻译：

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Aducanumab 和 Donanemab 在美国治疗早期阿尔茨海默病的成本效益。

重要性 已经开发了几种抗淀粉样蛋白单克隆抗体来减缓阿尔茨海默病 (AD) 的进展。其中开发最深入的是 aducanumab，它于 2021 年获得美国食品和药物管理局的加速批准，以及 donanemab，目前正在进行 3 期试验。这些治疗的成本效益尚未确定。目标 评估美国早期 AD 的标准治疗相对于 aducanumab 和 donanemab 的成本效益。设计、设置和参与者 使用决策分析模型从美国医疗保健部门和社会的角度估计患有早期 AD 的成年人的终生健康和经济结果。模拟患者的平均 (SD) 年龄为 75.2 (5.5) 岁；65% 的人有轻度认知障碍，35% 的人有轻度痴呆症。分析于 2021 年 4 月 6 日至 2022 年 1 月 20 日进行。干预措施 标准治疗，aducanumab（选定的输入包括疾病进展风险比 [HR] 为 0.89 [95% CI，0.63-1.15]，年价为 28,000 美元，以及每年两次脑部磁共振成像 [MRI] 监测）或多那单抗（选定的输入包括疾病进展 HR 为 0.68 [95% CI，0.44-0.99]，年价 28000 美元，每年两次 MRI 监测脑和淀粉样蛋白正电子发射断层扫描 [PET] 监测）。在 PET 成像显示淀粉样蛋白显着减少后，Donanemab 被转换为安慰剂，这发生在 6 个月时 27% 的患者和 12 个月时 55% 的患者。主要成果和措施质量调整生命年（QALYs）；成本，2020 美元；增量成本效益比（ICER）；基于价值的价格，定义为在 ICER 的成本效益阈值为 150 000 美元/QALY 的情况下治疗具有成本效益的最高价格。结果 终生 QALYs 使用 aducanumab 增加了 0.133，使用 donanemab 增加了 0.408。卫生保健部门和社会的总成本分别增加了 130 100 美元和 127 800 美元，使用 aducanumab，分别增加了 78 700 美元和 71 600 美元，使用 donanemab，主要受药物成本的推动（aducanumab 为 119 000 美元，donanemab 为 44 600 美元）。与标准护理相关的医疗保健部门和社会 ICER 分别为 981 000 美元/QALY 和 964 000 美元/QALY，对于 aducanumab，对于 donanemab 分别为 193 000 美元/QALY 和 176 000 美元/QALY。在敏感性分析中，即使假设疾病进展减少 90%，aducanumab 基于价值的价格仍低于 5 万美元/年。多纳单抗 一旦其疗效超过 50%，其基于价值的价格超过 50 000 美元/年。结论和相关性 这些研究结果表明，按照目前的预期价格，aducanumab 和 donanemab 对美国的早期 AD 都不具有成本效益。Donanemab 的剂量方案（患者在淀粉样蛋白显着减少时暂停治疗）可能提供一个标准，即使在与其他生物制剂价格相当的情况下，足够有效的抗淀粉样蛋白抗体治疗也可能具有成本效益。