Wang Guoqiao, Li Yan, McDade Eric, Xiong Chengjie, Hartz Sarah M, Bateman Randall J, Morris John C, Schneider Lon S
Department of Neurology, Washington University, School of Medicine, St. Louis, Missouri, USA.
Division of Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Alzheimers Dement. 2025 Sep;21(9):e70643. doi: 10.1002/alz.70643.
Clinical Dementia Rating Sum of Boxes (CDR-SB) is a reliable and clinically meaningful composite for assessing treatment effects in Alzheimer's disease (AD) clinical trials. Small CDR-SB differences at the end of a trial often lead to controversy in deriving clinically meaningful interpretations.
We estimated progression-free time (PFT) participants remained at each 0.5 unit CDR-SB increment in dominantly inherited AD (DIAD) and sporadic AD populations, evaluating its potential as an alternative measure of treatment effects.
PFT is longer at CDR-SB ≤ 2.0 (1-2 years) and shorter at CDR-SB ≥ 5 (≤ 0.33) in the Alzheimer's Disease Neuroimaging Initiative cohort. The DIAD cohort showed similar but shorter times. Using PFT, continuous lecanemab treatment for 3 years is estimated to delay disease progression by 0.62 years in the sporadic population.
PFT provides a benchmark for expressing clinical progression and treatment effects and can be applied particularly during open-label extensions and single-arm trials without placebo comparisons.
We estimated the progression-free time at each 0.5 unit Clinical Dementia Rating Sum of Boxes increment in dominantly inherited Alzheimer's disease (AD) and sporadic AD populations. We proposed using progression-free time to estimate treatment effects in open-label extension or single-arm studies. If further validated, progression-free time could serve as a benchmark for assessing clinical progression and treatment effects.
临床痴呆评定量表总和（CDR-SB）是一种可靠且具有临床意义的综合指标，用于评估阿尔茨海默病（AD）临床试验中的治疗效果。试验结束时CDR-SB的微小差异往往会在得出具有临床意义的解释时引发争议。
我们估计了显性遗传性AD（DIAD）和散发性AD人群中参与者在CDR-SB每增加0.5个单位时的无进展时间（PFT），评估其作为治疗效果替代指标的潜力。
在阿尔茨海默病神经影像倡议队列中，CDR-SB≤2.0（1 - 2年）时PFT较长，CDR-SB≥5（≤0.33）时PFT较短。DIAD队列显示出类似但更短的时间。使用PFT估计，在散发性人群中连续3年使用lecanemab治疗可使疾病进展延迟0.62年。
PFT为表达临床进展和治疗效果提供了一个基准，尤其可应用于开放标签扩展试验和无安慰剂对照的单臂试验。
我们估计了显性遗传性阿尔茨海默病（AD）和散发性AD人群中CDR-SB每增加0.5个单位时的无进展时间。我们建议在开放标签扩展或单臂研究中使用无进展时间来估计治疗效果。如果进一步验证，无进展时间可作为评估临床进展和治疗效果的基准。
