Utility of APOE testing for reducing ARIA under probabilistic stopping rates to treat with anti-amyloid therapy for ε4-homozygote patients: A simulation study - 25/01/26
, Yoshiki Niimi a, b, Masanori Kurihara c, Ryoko Ihara c, Atsushi Iwata c, Takeshi Iwatsubo a, b, d
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Abstract |
Background |
APOE ε4/ε4 genotype increases the risk of Amyloid-Related Imaging Abnormalities (ARIA) from anti-amyloid antibody treatment (AAT). While guidelines recommend testing, its practical utility depends on the resulting probability ( p ) that treatment is actually withheld for ε4-homozygotes, which varies significantly across clinical settings.
Objectives |
To quantify the Number Needed to Test (NNT) to prevent one ARIA event as a function of p of withholding AAT in ε4/ε4 patients.
Design |
A Bayesian simulation study using a Beta-Binomial model to analyze genotype-stratified contingency tables.
Setting |
Data were derived from two published, phase 3 clinical trials: Clarity-AD (lecanemab) and TRAILBLAZER-ALZ 2 (donanemab).
Participants |
Aggregate data from source trials.
Intervention |
Simulation of varying treatment discontinuation probability p from 0 (none) to 1 (universal for ε4-homozygotes).
Measurements |
NNT to prevent one ARIA event (any ARIA-E, any ARIA-H, and symptomatic ARIA-E) and the fractional reduction in total ARIA events as a function of p .
Results |
NNTs increased (worsened) significantly as p decreased. Under the most conservative policy ( p = 1), the median NNT to prevent one any ARIA-E event was 20–30 (lecanemab) and 15–25 (donanemab), yet this only reduced total ARIA events by 10–30%. The NNT to prevent one symptomatic ARIA-E (lecanemab) was substantially higher, at 70–90 (at p = 1).
Conclusions |
The direct safety impact of APOE testing for ARIA mitigation is limited, even under universal discontinuation policies. Its primary value lies in supporting shared decision-making and operational planning rather than as a standalone safety lever.
Le texte complet de cet article est disponible en PDF.Keywords : APOE, Anti-amyloid treatment, ARIA, Number needed to test, Alzheimer's Disease, Shared decision-making
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Vol 15
Article 100059- 2026 Retour au numéro
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