Lecanemab: Appropriate Use Recommendations by Korean Dementia Association

Abstract

Lecanemab (product name Leqembi®) is an anti-amyloid monoclonal antibody treatment approved for use in Korea for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. The Korean Dementia Association has created recommendations for the appropriate use of lecanemab to assist clinicians. These recommendations include selecting patients for administration, necessary pre-administration tests and preparations, administration methods, monitoring for amyloid related imaging abnormalities (ARIA), and communication with patients and caregivers. Lecanemab is recommended for patients with MCI or mild dementia who confirmed positive amyloid biomarkers, and should not be administered to patients with severe hypersensitivity to lecanemab or those unable to undergo magnetic resonance imaging (MRI) evaluation. To predict the risk of ARIA before administration, apolipoprotein E genotyping is conducted, and regular brain MRI evaluations are recommended to monitor for ARIA during treatment. The most common adverse reactions are infusion-related reactions, which require appropriate management upon occurrence. Additional caution is needed when co-administering with anticoagulants or tissue plasminogen activator due to the risk of macrohemorrhage. Clinicians should consider the efficacy and necessary conditions for administration, as well as the safety of lecanemab, to make a comprehensive decision regarding its use.

Keywords: Alzheimer's Disease; Amyloid; Lecanemab; Magnetic Resonance Imaging; Monoclonal Antibody.

Fig. 1. ARIA characteristics.

ARIA-E: amyloid related imaging abnormalities edema/effusion, ARIA-H: amyloid related imaging abnormalities hemosiderin/hemorrhage, FLAIR: fluid attenuated inversion recovery, GRE: gradient-recalled echo, SWI: susceptibility-weighted imaging, MRI: magnetic resonance imaging, DWI: diffusion-weighted imaging, ARIA: amyloid related imaging abnormalities.

Fig. 2. Impairment of perivascular clearance function in CAA and AD. (A) Healthy normal: in a healthy state, Aβ is removed from the brain along the perivascular space, following the arterial walls, through normal vascular structure and function. (B) AD: in AD, Aβ accumulates in both the brain parenchyma and blood vessels, damaging the vasculature and reducing the clearance of Aβ via the perivascular space. (C) CAA: as the clearance of Aβ via the perivascular space decreases, Aβ accumulates, resulting in a loss of vascular smooth muscle cells and reduced vascular activity, which further decreases Aβ clearance. This continuous decline in Aβ clearance leads to CAA-related vascular lesions, such as hemorrhages and tissue damage, worsening AD pathology.

Aβ: amyloid-beta, AD: Alzheimer's disease, CAA: cerebral amyloid angiopathy.

Fig. 3. Hypothesis of ARIA related to amyloid clearance. (A) Initial stage of anti-amyloid immunotherapy: anti-amyloid immunotherapy induces an immune response against Aβ as it moves from the brain parenchyma to the perivascular clearance pathway. This immune response can worsen cerebral amyloid angiopathy, causing leakage of proteinaceous fluid and blood components out of the vessels, leading to amyloid-related imaging abnormalities (ARIA; specifically ARIA-E and ARIA-H). (B) Repeated administration of anti-amyloid immunotherapy: with repeated anti-amyloid immunotherapy, Aβ is continuously cleared via the perivascular clearance pathway, improving the efficiency of this clearance over time. Consequently, the risk of ARIA decreases.

Aβ: amyloid-beta, ARIA: amyloid related imaging abnormalities, ARIA-E: amyloid related imaging abnormalities edema/effusion, ARIA-H: amyloid related imaging abnormalities hemosiderin/hemorrhage.

Fig. 4. MRI monitoring schedule. It is recommended to confirm the presence or absence of pre-existing ARIA with a recent (within one year) brain MRI before starting treatment. During treatment, MRIs should be performed before the 5^th, 7^th, and 14^th infusions for monitoring. For patients who are APOE4 carriers or who have confirmed ARIA in previous monitoring, additional monitoring before the 26^th infusions could be considered based on the clinician's judgment. Furthermore, beyond the basic and regular MRI examinations, if suspected ARIA symptoms arise, additional MRI scans can be performed alongside clinical evaluations to assess ARIA.

MRI: magnetic resonance imaging, ARIA: amyloid related imaging abnormalities, APOE4: apolipoprotein E ε4 allele. ^*APOE4 carriers or those with previous ARIA in previous monitoring.