Tahami Monfared Amir Abbas, Ye Weicheng, Sardesai Aditya, Folse Henri, Chavan Ameya, Aruffo Elena, Zhang Quanwu
Eisai Inc., 200 Metro Blvd., Nutley, NJ, 07110, USA.
Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
Neurol Ther. 2023 Jun;12(3):863-881. doi: 10.1007/s40120-023-00473-w. Epub 2023 Apr 2.
Alzheimer's disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and one of the leading causes of death for elderly people in the USA. Lecanemab is a humanized IgG1 monoclonal antibody targeting amyloid protofibrils for the treatment of early AD [i.e., mild cognitive impairment (MCI) or mild AD dementia]. In a recent 18-month phase III trial, using a double-blind, placebo-controlled design, lecanemab treatment led to reduced brain amyloid burden and significant improvements in cognitive and functional abilities in individuals with early AD.
An evidence-based patient-level disease simulation model was updated to estimate the long-term health outcomes of lecanemab plus standard of care (SoC) compared to SoC alone in patients with early AD and evidence of brain amyloid burden, using recent phase III trial data and published literature. The disease progression is described by changes in the underlying biomarkers of AD, including measures of amyloid and tau, and their connection to the clinical presentation of the disease assessed through various patient-level scales of cognition and function.
Lecanemab treatment was estimated to slow the progression of AD to moderate and severe stages and reduce the time spent in these more advanced states. In individuals with early AD, lecanemab plus SoC was associated with a gain of 0.71 quality-adjusted life-years (QALYs), a 2.95-year delay in mean time to progression to AD dementia, a reduction of 0.11 years in institutional care, and an additional 1.07 years in community care as shown in the base-case study. Improved health outcomes were demonstrated with lecanemab treatment when initiated earlier based on age, disease severity, or tau pathology, resulting in estimated gains in QALYs ranging from 0.77 to 1.09 years, compared to 0.4 years in the mild AD dementia subset, as shown by the model.
The study findings demonstrate the potential clinical value of lecanemab for individuals with early AD by slowing down disease progression and prolonging time in earlier stages of disease, which significantly benefits not only patients and caregivers but also society overall.
ClinicalTrials.gov identifier, NCT03887455.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，是痴呆症的主要病因，也是美国老年人的主要死因之一。莱卡奈单抗是一种靶向淀粉样原纤维的人源化IgG1单克隆抗体，用于治疗早期AD[即轻度认知障碍（MCI）或轻度AD痴呆]。在最近一项为期18个月的III期试验中，采用双盲、安慰剂对照设计，莱卡奈单抗治疗可减轻早期AD患者的脑淀粉样蛋白负担，并显著改善其认知和功能能力。
使用最近的III期试验数据和已发表的文献，更新了一个基于证据的患者水平疾病模拟模型，以估计在早期AD且有脑淀粉样蛋白负担证据的患者中，与单独使用标准治疗（SoC）相比，莱卡奈单抗加SoC的长期健康结局。疾病进展通过AD潜在生物标志物的变化来描述，包括淀粉样蛋白和tau的测量，以及它们与通过各种患者水平认知和功能量表评估的疾病临床表现的联系。
据估计，莱卡奈单抗治疗可减缓AD进展至中度和重度阶段，并减少在这些更晚期状态下花费的时间。在早期AD患者中，如基础病例研究所示，莱卡奈单抗加SoC与0.71个质量调整生命年（QALY）的获益、进展至AD痴呆的平均时间延迟2.95年、机构护理时间减少0.11年以及社区护理时间增加1.07年相关。模型显示，根据年龄、疾病严重程度或tau病理学更早开始使用莱卡奈单抗治疗可改善健康结局，估计QALY获益范围为0.77至1.09年；相比之下，轻度AD痴呆亚组为0.4年。
研究结果表明，莱卡奈单抗对早期AD患者具有潜在的临床价值，可减缓疾病进展并延长疾病早期阶段的时间，这不仅使患者和护理人员显著受益，也使整个社会受益。
ClinicalTrials.gov标识符，NCT03887455。
