Lecanemab shows favorable real-world safety in Korean registry study of 663 patients

A nationwide registry study from South Korea reports that lecanemab, an amyloid-targeting antibody for Alzheimer’s disease, showed favorable safety and short-term clinical outcomes when delivered under routine clinical conditions rather than the controlled setting of a randomized trial. The analysis drew on the Korean Joint Registry for Alzheimer’s Treatment and Diagnostics, known as JOY-ALZ, and was published in Alzheimer’s Research & Therapy.

The study included 663 participants with Alzheimer’s disease who received at least one lecanemab infusion at 32 hospitals across the country. For the analyses of amyloid-related imaging abnormalities, or ARIA, the investigators focused on 657 patients who had undergone at least one monitoring MRI. ARIA refers to fluid changes or microbleeds that can appear on brain scans during treatment with anti-amyloid therapies and are a key safety concern for this drug class.

Overall, ARIA occurred in 106 patients, or 16.1 percent of those monitored. This comprised ARIA with edema or effusion, with or without accompanying hemorrhage or hemosiderin deposition, in 27 patients (4.1 percent), and isolated ARIA with hemorrhage or hemosiderin deposition in 79 patients (12.0 percent). Only four patients, 0.6 percent, developed symptomatic ARIA, and all of these cases involved ARIA with edema. The low proportion of symptomatic events is a central finding of the report.

The registry data allowed the researchers to identify which patient characteristics were independently associated with developing ARIA with edema. APOE ε4 homozygosity carried a hazard ratio of 2.81 (95 percent confidence interval 1.06 to 7.46). Higher Clinical Dementia Rating-Sum of Boxes scores were associated with a hazard ratio of 1.18 per point (95 percent CI 1.04 to 1.35). Each additional baseline microhemorrhage raised the hazard by a factor of 1.69 (95 percent CI 1.32 to 2.16), and the presence of baseline superficial siderosis was linked to a hazard ratio of 7.45 (95 percent CI 1.50 to 37.12). These factors may support risk stratification when clinicians weigh treatment decisions.

Notably, the incidences of ARIA with edema and ARIA with hemorrhage did not differ between the standard-dose and titration-dose groups within each APOE ε4 genotype group in this observational dataset.

Infusion-related reactions occurred in 26.7 percent of participants and were less frequent among those who received dose titration.

On the clinical outcome side, Mini-Mental State Examination scores declined over the observation period at a modeled rate of 0.15 points per month (95 percent CI 0.21 to 0.08; P < 0.001), with less decline observed in patients who had mild cognitive impairment rather than dementia and in those with late-onset Alzheimer’s disease. Higher baseline plasma p-tau217 levels were associated with greater worsening in functional activities. These are short-term registry observations over a limited follow-up window and do not establish long-term efficacy.

The study also tracked biomarker response. Amyloid PET negativity was achieved in 23.4 percent of patients (15 of 64) at 3 to 9 months and in 27.6 percent (8 of 29) at 10 to 12 months. Achieving amyloid clearance on PET was independently associated with lower baseline Centiloid values, with an odds ratio of 0.92 per unit (95 percent CI 0.88 to 0.96), and with higher baseline MMSE scores, with an odds ratio of 1.23 (95 percent CI 1.04 to 1.45). In other words, patients who started with less amyloid burden and better cognition were more likely to reach amyloid negativity during treatment.

The authors conclude that lecanemab showed favorable real-world safety and short-term clinical outcomes in this registry, and that the findings may inform patient selection, ARIA risk stratification, treatment optimization, and biomarker-informed treatment strategies in clinical practice. As a multicenter observational study of 663 patients treated across 32 Korean hospitals, it offers one of the broader real-world pictures of lecanemab delivery to date, while remaining subject to the limitations of non-randomized design, clinician-directed dosing decisions, and the relatively short follow-up captured in the registry.

Subject of Research: Real-world safety and short-term outcomes of lecanemab in Alzheimer's disease from the Korean JOY-ALZ registry

Article Title: 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)

Article References: Kang, S. H., Jeong, J. H., Lim, J.-S., Park, K. H., Kim, G. H., Koh, S.-H., Yang, D. W., Choi, H., Kim, H. S., Moon, Y., Moon, S. Y., Kim, E.-J., Kwon, J. C., Kang, D., Oh, S., Lee, Y.-G., Lee, E. A., Park, Y. H., Pyun, J.-M., … Choi, S. H. (2026). 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). Alzheimer's Research & Therapy. https://doi.org/10.1186/s13195-026-02232-z

Image Credits: AI Generated

DOI: 10.1186/s13195-026-02232-z

Keywords: lecanemab, Alzheimer's disease, ARIA, JOY-ALZ registry, APOE ε4, amyloid PET, p-tau217, dose titration, infusion-related reactions, real-world evidence, MMSE, superficial siderosis