Lecanemab and other anti-amyloid antibodies

APOE genotype predicts how likely a person is to develop ARIA — amyloid-related imaging abnormalities, meaning brain swelling or small bleeds seen on MRI — during anti-amyloid antibody treatment. In the pivotal trial, ARIA of any kind occurred in about 45% of e4 homozygotes, 19% of heterozygotes and 13% of non-carriers on lecanemab, and symptomatic ARIA with brain swelling in about 9% of e4 homozygotes versus roughly 2% of heterozygotes and 1% of non-carriers. US prescribing information therefore states that APOE e4 status should be determined before starting treatment so that this risk can be discussed. This is risk information for people already diagnosed and under specialist care; it is not treatment or dosing advice, and nothing here should be used to start, stop or change any medicine.

FDA prescribing information for LEQEMBI (lecanemab-irmb); Dean L, Kane M. Lecanemab Therapy and APOE Genotype. Medical Genetics Summaries, NCBI Bookshelf NBK605938. Note: this is an FDA-label association, not a CPIC guideline — CPIC has no APOE guideline (its only listed APOE pair, with atorvastatin, is CPIC level D).