Are pre-frail and frail amyloid positive individuals eligible to Lecanemab? A cross-sectional analysis from the Cogfrail real-world cohort

TL;DR

This study examines whether frail and pre-frail individuals with amyloid positivity can be treated with Lecanemab, finding that real-world guidelines allow more eligibility than the original trial.

Contribution

The study applies Lecanemab eligibility criteria to a real-world cohort of pre-frail and frail individuals with amyloid positivity.

Findings

Only 9.1% of frail individuals met the Clarity-AD trial criteria, compared to 26.3% of pre-frail participants.

Approximately half of the cohort was potentially eligible for Lecanemab under real-world recommendations.

Frailty was underrepresented in the Clarity-AD trial, raising concerns about generalizability to frail populations.

Abstract

Following the positive outcomes of the Clarity-AD trial, Lecanemab received marketing authorization from the European Medicines Agency (EMA) and is expected to become available across Europe. However, the trial did not specifically evaluate frailty, making it difficult to estimate the potential effects of Lecanemab among frail individuals. This study aimed to apply Lecanemab eligibility criteria—based on both the Clarity-AD trial and the Appropriate Use Recommendations (AUR) from the United States and France—to a real-world population of pre-frail and frail older adults with confirmed positive amyloid status, and to evaluate differences in frailty status between eligible and non-eligible patients.

Eligibility criteria from the Clarity-AD trial, the American and the French AUR, were applied to all participants with confirmed amyloid positivity (n = 120), assessed through amyloid-PET (visual reading) or cerebrospinal fluid (CSF) analysis (Aβ42 levels or Aβ42/Aβ40 ratio). Frailty was defined using the Fried phenotype.

The median age of the sample was 82.0 years (IQR: 79–85); 65% (n = 78) were women, and 36.7% (n = 44) were frail. Overall, 20.0% (n = 24) met the Clarity-AD eligibility criteria, while 50.8% (n = 61) and 47.5% (n = 57) were potentially eligible according to the American and French AURs, respectively. Only 9.1% (n = 4) of frail individuals met the Clarity-AD criteria, compared to 26.3% (n = 20) of pre-frail participants (p = 0.042). In contrast, 50.0% (n = 22) and 45.5% (n = 20) of frail individuals were potentially eligible according to the American and French AURs, respectively.

Although less than one in five participants would have been eligible for the Clarity-AD trial, approximately half the cohort would be potentially treatable with Lecanemab under real-world recommendations. While a considerable proportion of frail patients may have access to Lecanemab treatment in real-life, the low proportion of potentially eligible frail individuals for Clarity-AD in our cohort indirectly suggests that frailty may have been underrepresented in the trial, raising concerns about the generalizability of its findings to this population. Caution is warranted when targeting amyloid burden without previously addressing the underlying frailty.

NCT03129269.

The online version contains supplementary material available at 10.1186/s13195-026-01966-0.

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