Efficacy and Safety of Lecanemab in Early Alzheimer's Disease: A Meta-analysis of Clinical Trials
Marianna Leite1, Anderson M. Pereira da Silva2, Anderson Corin3, Abhishek Goyal4, João Vitor Fernandes5, Mariana Letícia Maximiano6, Diogo Haddad Santos7, Carolina Moura7
1School of Public Health, Department of Epidemiology, University of São Paulo, São Paulo, Brazil. Santa Marcelina School of Medicine, São Paulo, Brazil, 2Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE, Brazil, 3Federal University of Pelotas, 4JFK University Medical Center, Edison, New Jersey, USA, 5Medical Sciences Center, Federal University of Paraíba, João Pessoa, Brazil, 6Federal Fluminense University, 7Santa Casa de Misericórdia de São Paulo, SP, Brazil
Objective:
This meta-analysis aims to synthesize evidence from clinical trials to quantify Lecanemab's efficacy on key cognitive, functional, and biomarker outcomes, and to determine the pooled incidence of its primary safety concerns, ARIA-E and ARIA-H.
Background:
Lecanemab, an anti-amyloid monoclonal antibody, has emerged as a promising disease-modifying therapy for early Alzheimer's disease. Clinical trials have evaluated its impact on various outcomes, including cognitive and functional decline, measured by CDR-SB, ADAS-Cog 14 and ADCOMS; amyloid plaque burden - Amyloid PET, and safety, particularly the incidence of and Amyloid-Related Imaging Abnormalities ARIA-E and ARIA-H. However, a consolidated view of its effect size across studies is essential for clinical context.
Design/Methods:
We performed a random-effects meta-analysis on published clinical trials reporting outcomes for Lecanemab versus placebo. We analyzed the mean difference (MD) for efficacy outcomes and the pooled proportion for safety events. Heterogeneity was assessed using the I² statistic.
Results:
Six studies including 4,862 patients were analyzed. Lecanemab significantly slowed cognitive decline with low heterogeneity on the CDR-SB (MD -0.48, 95% CI: -0.80 to -0.15, p<0.05, I²=0%), ADAS-Cog 14 (MD -1.36, 95% CI: -1.79 to -0.94, p<0.01, I²=0%) and ADCOMS (MD -47.92, 95% CI: -53.59 to -42.24, p < 0.01, I² = 98%). It also showed a substantial reduction in amyloid plaque burden on PET scans (MD -54.58, 95% CI: -150.94 to 41.78, p = 0.13, I² = 96%). The pooled incidence of ARIA-E was 13% (95% CI: 11% to 14%) with low heterogeneity (I²=10%), while the incidence of ARIA-H was 11% (95% CI: 7% to 15%) with high heterogeneity (I²=86%).
Conclusions:
This meta-analysis confirms that Lecanemab provides statistically significant clinical benefits in slowing cognitive decline and reducing amyloid pathology in patients with early Alzheimer's disease. These benefits must be weighed against a notable risk of ARIA, highlighting the critical need for careful patient selection and safety monitoring.
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