Clinical progression on CDR-SB©: Progression-free time at each 0.5 unit level in dominantly inherited and sporadic Alzheimer's disease populations

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. Highlights: 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.