When should a physician consider stopping IV lecanemab (anti-amyloid therapy) in patients with Alzheimer's disease?

When to Stop IV Lecanemab Therapy

Physicians should suspend or permanently discontinue lecanemab when patients develop moderate-to-severe symptomatic ARIA-E, severe radiographic ARIA-E (even if asymptomatic), severe radiographic ARIA-H, intracerebral hemorrhage >1 cm, or recurrent ARIA-E episodes. 1

Mandatory Suspension Scenarios for ARIA-E

Suspend dosing immediately in the following situations: 1

• Moderate or severe symptomatic ARIA-E (regardless of radiographic severity) - symptoms include headache, confusion, visual disturbances, dizziness, gait difficulties, or incapacitating symptoms preventing normal daily activities 2, 1
• Asymptomatic moderate radiographic ARIA-E - FLAIR hyperintensity 5-10 cm in greatest dimension or multiple sites each <10 cm 1
• Asymptomatic severe radiographic ARIA-E - FLAIR hyperintensity >10 cm with gyral swelling and sulcal effacement 1
• Mild symptomatic ARIA-E with any radiographic severity - suspend based on clinical judgment 1

Resumption criteria: Only resume after MRI demonstrates complete radiographic resolution AND all symptoms resolve; consider follow-up MRI 2-4 months after initial identification 1

Mandatory Suspension Scenarios for ARIA-H

Suspend dosing for: 1

• Moderate radiographic ARIA-H (5-9 new microhemorrhages OR 2 focal areas of superficial siderosis) - whether symptomatic or asymptomatic 1
• Severe radiographic ARIA-H (≥10 new microhemorrhages OR >2 areas of superficial siderosis) - whether symptomatic or asymptomatic 1
• Any symptomatic ARIA-H with mild radiographic findings (≤4 new microhemorrhages OR 1 focal area of superficial siderosis) 1

Resumption criteria: Resume only after MRI demonstrates radiographic stabilization AND symptoms resolve; follow-up MRI recommended 2-4 months after initial identification 1

Permanent Discontinuation Considerations

Use clinical judgment to consider permanent discontinuation in: 1

• Intracerebral hemorrhage >1 cm diameter - suspend until radiographic stabilization and symptom resolution, then decide whether to continue or permanently stop 1
• Severe radiographic ARIA-H - particularly if asymptomatic, as there is limited safety data on continuing treatment 1
• Recurrent ARIA-E episodes - there are limited data on dosing patients with recurrent ARIA-E; use clinical judgment 1
• Concurrent anticoagulation or thrombolytic therapy - three deaths occurred in clinical trials with concurrent ICH (one on tissue plasminogen activator, one on anticoagulant therapy) 3

High-Risk Populations Requiring Enhanced Vigilance

APOE ε4 homozygotes face substantially elevated ARIA risk: 1, 3

• Severe radiographic ARIA-E: 5% in ε4/ε4 homozygotes vs 0.4% in heterozygotes vs 0% in non-carriers 1
• Severe radiographic ARIA-H: 13.5% in ε4/ε4 homozygotes vs 2.1% in heterozygotes vs 1.1% in non-carriers 1
• ARIA-E overall: 34.5% in ε4/ε4 homozygotes vs 16.8% in heterozygotes 3

Consider lower threshold for discontinuation in these patients given their disproportionate risk. 1, 3

Critical Monitoring Timeline

Enhanced clinical vigilance is mandatory during the first 14 weeks (first 7 doses) when ARIA-E most commonly occurs: 1

• Obtain MRI prior to 5th, 7th, and 14th infusions 1
• Perform immediate MRI for any new neurological symptoms at any time during treatment 2, 1
• 52% of ARIA-E cases resolve by 12 weeks, 81% by 17 weeks, and 100% eventually resolve after detection 1

Novel Safety Concerns

Emerging evidence suggests ischemic strokes may be a feature of ARIA: 4

• One case report documented multiple ischemic strokes occurring alongside typical ARIA findings (microhemorrhages and cerebral edema) 4
• The same patient experienced frequent electrographic seizures without overt clinical seizures, highlighting the need for high clinical suspicion for seizures in ARIA 4
• Consider discontinuation if ischemic events occur in the context of ARIA 4

Important Caveats

There is no clinical trial experience with: 1

• Continuing dosing through symptomatic ARIA-E
• Continuing dosing through asymptomatic but radiographically severe ARIA-E
• Limited experience continuing through asymptomatic mild-to-moderate ARIA-E
• Limited data on patients with recurrent ARIA-E

The FDA label explicitly states to use clinical judgment when deciding whether to continue or permanently discontinue in severe ARIA-H cases and intracerebral hemorrhage >1 cm. 1