What is the risk of amyloid-related imaging abnormalities (ARIA) for an 83-year-old patient with an APOE (Apolipoprotein E) genotype of E2/E4 taking Leqembi (lecanemab)?

ARIA Risk for an 83-Year-Old with APOE E2/E4 on Leqembi

An 83-year-old patient with APOE E2/E4 genotype taking Leqembi (lecanemab) has a moderate risk of developing ARIA, with approximately 7.1% risk of ARIA-E based on their heterozygous APOE ε4 carrier status. 1, 2

ARIA Risk Based on APOE Status

• APOE ε4 carrier status is a significant risk factor for developing Amyloid-Related Imaging Abnormalities (ARIA), with heterozygous carriers (like E2/E4) having approximately 7.1% risk of ARIA-E compared to 33% in homozygous ε4/ε4 carriers and only 4.3% in non-carriers 1
• The FDA label for Leqembi specifically notes that "the risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers" 2
• Your patient with E2/E4 genotype falls into the heterozygous carrier category, placing them at moderate risk 1

Types of ARIA and Clinical Presentation

• ARIA consists of two main types:

  • ARIA-E: temporary swelling in areas of the brain (edema)
  • ARIA-H: small spots of bleeding in or on the surface of the brain (microhemorrhages and superficial siderosis) 2

• Most ARIA cases (approximately 60%) are asymptomatic and detected only on routine MRI monitoring 1, 3

• When symptomatic, patients may experience:

  • Headache
  • Confusion
  • Dizziness
  • Visual disturbances
  • Nausea
  • Aphasia
  • Weakness
  • Seizures (rare) 2, 3

Timing and Monitoring

• ARIA-E typically occurs within the first 3-6 months of treatment initiation 3
• The FDA recommends enhanced clinical vigilance for ARIA during the first 14 weeks of treatment with Leqembi 2
• Regular MRI monitoring is essential for early detection of ARIA, even in asymptomatic cases 2

Risk Factors That May Increase ARIA Risk in This Patient

• Advanced age (83 years) may increase the risk of ARIA-H (microhemorrhages) 4
• Pre-existing microhemorrhages or superficial siderosis would further increase the risk of both ARIA-E and ARIA-H 2
• Concurrent use of anticoagulants or antithrombotic medications would significantly increase the risk of brain hemorrhage 5, 2

Management Considerations

• If ARIA is detected:

  • Asymptomatic ARIA: May continue treatment with close MRI monitoring 1, 3
  • Symptomatic ARIA: May require temporary or permanent discontinuation of treatment depending on severity 4
  • Severe symptomatic ARIA: May require treatment with corticosteroids in some cases 4, 6

• Patients should be educated about potential ARIA symptoms and instructed to report them immediately 2

• Regular MRI monitoring is essential, especially during the first few months of treatment 2

Important Caveats

• While rare, fatal cases of ARIA have been reported with anti-amyloid antibodies 4, 3
• The risk of macrohemorrhage is increased when Leqembi is used concurrently with anticoagulants or tissue plasminogen activator 7, 3
• The benefit-risk profile should be carefully considered in this 83-year-old patient, as advanced age may increase vulnerability to adverse events 4