Safety, short-term clinical outcomes, and associated factors of lecanemab: a multicenter real-world study from the Korean Joint Registry for Alzheimer’s Treatment and Diagnostics (JOY-ALZ)

Identifying patient characteristics and treatment strategies associated with better outcomes of lecanemab is important in clinical practice. We evaluated the real-world safety and short-term outcomes of lecanemab and factors associated with these outcomes using the Korean Joint Registry for Alzheimer’s Treatment and Diagnostics (JOY-ALZ). We analyzed data from 663 participants with Alzheimer’s disease (AD) who received at least one lecanemab infusion at 32 hospitals nationwide. Amyloid-related imaging abnormality (ARIA) analyses included 657 patients who underwent at least one monitoring MRI. Dose titration was used at the clinician’s discretion in 74.7% of APOE ε4 homozygotes, 50.5% of heterozygotes, and 32.7% of noncarriers. ARIA occurred in 106 patients (16.1%): ARIA with edema/effusion (ARIA-E) with or without ARIA with hemorrhage/hemosiderin deposition (ARIA-H) in 27 (4.1%) and isolated ARIA-H in 79 (12.0%). Symptomatic ARIA occurred in four patients (0.6%) with ARIA-E. APOE ε4 homozygosity (hazard ratio [HR] 2.81; 95% confidence interval [CI] 1.06–7.46), higher Clinical Dementia Rating-Sum of Boxes score (HR 1.18; 95% CI 1.04–1.35), greater number of baseline microhemorrhages (HR 1.69; 95% CI 1.32–2.16), and baseline superficial siderosis (HR 7.45; 95% CI 1.50–37.12) were independently associated with ARIA-E. The incidences of ARIA-E and ARIA-H did not differ between standard-dose and titration-dose groups within each APOE ε4 genotype group. Infusion-related reactions occurred in 26.7% and were less frequent with dose titration. Mini-Mental State Examination (MMSE) scores declined over time (β = −0.15 points/month, 95% CI − 0.21 to − 0.08; P < 0.001), with less decline in patients with mild cognitive impairment and late-onset AD. Higher baseline plasma p-tau217 levels were associated with greater worsening in functional activities. Amyloid PET negativity was achieved in 23.4% (15/64) at 3–9 months and 27.6% (8/29) at 10–12 months and was independently associated with lower baseline Centiloid values (OR 0.92; 95% CI 0.88–0.96) and higher baseline MMSE scores (OR 1.23; 95% CI 1.04–1.45). Lecanemab showed favorable real-world safety and short-term clinical outcomes. These findings may inform patient selection, ARIA risk stratification, treatment optimization, and biomarker-informed treatment strategies in clinical practice.