Lecanemab: Appropriate Use Recommendations.

Area of Science:

• Neurology
• Pharmacology
• Clinical Practice Guidelines

Background:

• Lecanemab (Leqembi®) is approved for early Alzheimer's disease (AD) with confirmed amyloid pathology.
• Real-world clinical practice differs from clinical trial settings, necessitating specific guidance for community-based administration.
• Existing data from phase 2 and 3 trials inform the safety and efficacy profile of lecanemab.

Purpose of the Study:

• To provide Appropriate Use Recommendations (AURs) for the safe and effective introduction of lecanemab into clinical practice.
• To guide clinicians in administering lecanemab, considering patient populations and administration settings distinct from clinical trials.
• To detail monitoring guidelines for potential adverse events associated with lecanemab treatment.

Main Methods:

• Adherence to inclusion and exclusion criteria from lecanemab phase 2 and 3 clinical trials.
• Integration of clinical trial data with broader research and care information for Alzheimer's disease.
• Development of protocols for managing adverse events, including amyloid-related imaging abnormalities (ARIA) and infusion reactions.

Main Results:

• Lecanemab treatment carries risks, including ARIA (most asymptomatic, some serious/fatal), microhemorrhages, and macrohemorrhages.
• Patients requiring anticoagulation are advised against lecanemab until further data are available due to increased hemorrhage risk.
• APOE ε4 gene carriers, particularly homozygotes, face a higher ARIA risk, necessitating genotyping for informed patient discussions.

Conclusions:

• Clinician and institutional preparedness, including protocols for serious event management, are crucial for lecanemab use.
• Open communication between clinicians and patients/care partners regarding benefits, harms, and monitoring is essential.
• Building trust and employing culture-specific communication strategies are foundational for successful lecanemab therapy.