Developing Topics.

For Alzheimer's disease (AD), there are currently two FDA-approved agents developed as disease-modifying treatments. Approval of lecanemab (Leqembi®) in 2023, via accelerated approval mechanism, followed by traditional approval accompanied by medical coverage decision by the Center for Medicare Services, has resulted in increasing use of this anti-amyloid monoclonal antibody, demonstrated in 18-month long clinical trials to slow Alzheimer's disease. Despite a broad package insert (with only contraindication product severe hypersensitivity), nationwide prescriptions have been reportedly affected by concerns regarding drug eligibility, monitoring, and whether real-world experience would mirror clinical trial data. In our practice, prescription of the medication has been contingent upon: (a) diagnosis of AD, (b) early stage of AD, (c) amyloid confirmation by CSF or PET, (d) acceptable ARIA-H at baseline MRI, and (e) non-mandatory apolipoprotein-E genotyping. Here we present data on the first 85 patients prescribed lecanemab at our center. Patient age is 73±8 yr (51-88) and sex 51% women, with 82% accepting apolipoprotein-E4 testing (42% non-carriers, 44% heterozygotes, and 14% homozygotes). Barriers associated with our above eligibility criteria (a) through (e) have been minimal. Similarly, barriers have generally not been large for MRI monitoring and infusion center availability; but during this first year of drug availability there have been challenges in coverage by insurers/payors other than standard original Medicare. Patients/families have had strong interest in this drug, with apparent good understanding and acceptance of risks of ARIA-E and ARIA-H. Patients deemed not eligible by their treating practitioners have been declined for the following reasons in descending order of frequency: disease too severe, non-Alzheimer's dementia (no amyloid confirmation), logistical (travel/time) considerations, disease too mild (presymptomatic), and excessive ARIA-H on baseline MRI. Overall, with up to 21 infusions per patient, adverse event rates have been similar to those in clinical trials with 7% ARIA-E (all asymptomatic), and low rates of infusion reactions. Suspension or discontinuation of therapy has occurred in 9% (7% due to ARIA, 1% due to persistent infusion reactions, 2% due to disinterest). Overall findings at our center suggest that experience in clinical use may not be dissimilar to that in the clinical trials.