ARIA With Monoclonal Antibody Treatments for Alzheimer Disease

EP: 1.Presentation of Alzheimer’s Disease in Clinical Practice

EP: 2.Diagnosis and Treatment of Alzheimer’s Disease

EP: 3.Lecanemab for Treatment of Early Alzheimer Disease

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EP: 4.ARIA With Monoclonal Antibody Treatments for Alzheimer Disease

EP: 5.Clarity-AD-OLE Study in Alzheimer’s Disease

EP: 6.Continuous Dosing of Lecanemab for Alzheimer’s Disease

Summary for Physicians

Managing ARIA Risk in Patients Receiving Lecanemab or Donanemab

Both lecanemab and donanemab carry a boxed warning for amyloid-related imaging abnormalities (ARIA), which can manifest as edema (ARIA-E) and/or microhemorrhages or superficial siderosis (ARIA-H). While often asymptomatic, symptomatic ARIA can cause headache, confusion, dizziness, visual changes, nausea, or seizures.

Clinical Management of ARIA

1. Baseline Screening and Risk Stratification

• Baseline MRI is required prior to initiating therapy to assess for:

• Microhemorrhages

• Siderosis

• Any preexisting edema or lesions

• APOE ε4 carrier status may influence ARIA risk, with higher incidence in carriers, particularly homozygotes. Testing is often recommended but not mandatory.

2. Monitoring Protocol

• Scheduled MRIs:

• At baseline

• Prior to the 5th, 7th, and 14th infusions (for lecanemab)

• Or as clinically indicated if symptoms arise

• Routine symptom surveillance during and between infusions (eg, headache, confusion, dizziness)

• Neurologic assessments are integrated into infusion visits to monitor for early signs of ARIA.

3. Management of Detected ARIA

• Asymptomatic ARIA:

• Mild cases: Often monitored without treatment interruption.

• Moderate to severe: May require temporary holding of therapy with repeat MRI monitoring.

• Symptomatic ARIA:

• Therapy is held immediately.

• Supportive care provided based on symptoms (eg, corticosteroids for severe edema).

• Neurology consult and close imaging follow-up.

• Re-challenge decisions are made on a case-by-case basis after resolution.

Operational Considerations

• Multidisciplinary Coordination: Neurologists, radiologists, infusion nurses, and care navigators are key to safe delivery.

• Patient Education: Patients and caregivers are counseled on ARIA risks, symptoms to watch for, and the importance of adhering to MRI schedules.

• Documentation and Communication: Clear protocols and electronic medical record reminders support consistent risk tracking and decision-making.

Key Takeaway

Managing ARIA requires structured protocols, proactive imaging, and early symptom recognition, balancing safety with the potential benefits of amyloid-lowering therapy in early Alzheimer disease.