Real-world ARIA on lecanemab reached 34% in APOE ε4 homozygotes against 11% in non-carriers

Design

Systematic review and meta-analysis of 37 real-world studies

Population

People with Alzheimer's disease treated with lecanemab outside trials

Primary outcome

ARIA incidence, discontinuation, cognitive scores and amyloid PET

Effect

Any ARIA 15.1%; ε4 homozygotes 34.1%, heterozygotes 14.5%, non-carriers 11.0%; symptomatic ARIA 1.3%

This meta-analysis pooled 37 real-world studies of lecanemab, keeping the largest dataset where cohorts overlapped. It looked at amyloid-related imaging abnormalities (ARIA), discontinuation and cognitive and imaging outcomes.

Any ARIA occurred in about 15% of patients, rising to 34% in APOE ε4 homozygotes. Baseline microbleeds were linked to more haemosiderin-type ARIA but not more oedema. Symptomatic ARIA was uncommon. Amyloid PET fell as expected, but cognitive scores showed no significant change, which cannot be interpreted without a comparison group.

The practical value is in the safety numbers by genotype and microbleed status. Lecanemab's availability and approval status in India should be confirmed before discussing it with patients.

• Any ARIA occurred in 15% overall; symptomatic ARIA in 1.3%.
• Baseline microbleeds roughly doubled the rate of any ARIA (23% vs 12%).
• ARIA was more frequent in US cohorts (20%) than Asian ones (10%).
• About 12% stopped treatment, 3.5% because of ARIA.
• Infusion reactions occurred in about 18%; plan for them at the first doses.

Why it matters

Real-world safety now broadly matches the trials, and it gives clinicians concrete numbers by genotype to use when consenting patients.

Don't overread it

Without control groups, these studies cannot show whether lecanemab slowed decline in practice.

The statistics, in plain English

The rates are pooled proportions from uncontrolled studies. The regional difference may reflect monitoring intensity or genotype mix rather than true biological difference.

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