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

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.