OBJECTIVES: Alzheimer’s disease (AD) causes a decline in memory, thinking, learning, and organizing skills. It’s the most common cause of dementia and usually affects people over the age of 65. AD is characterized by the accumulation of beta-amyloid protein in the brain. We reviewed the clinical evidence for lecanemab, a humanized monoclonal antibody that binds with high affinity to soluble amyloid-beta protofibrils, for treating early AD.

METHODS: A systematic search of published literature was performed using Embase^® and MEDLINE^® from database inception to June 2023 to identify the randomized controlled trials assessing lecanemab in early AD. The outcomes of interest included change from baseline in Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), Alzheimer’s Disease Composite Score (ADCOMS), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) at 18 months. The meta-analysis was performed using Stata 17 software.

RESULTS: Two double-blind, placebo-controlled, 18-month trials (Study 201, and Clarity AD) met the inclusion criteria. Both trials were broadly similar in terms of methodological and clinical characteristics. Lecanemab 10 mg biweekly was associated with statistically significantly better efficacy vs. placebo in terms of reduction in CDR-SB (WMD, 95%CI: -0.44, -0.70 to -0.17), ADCOMS (-0.05, -0.07 to -0.03), and ADAS-Cog14 (-1.55, -2.30 to -0.79) scales. A sensitivity analysis performed using data from different analysis types i.e., MMRM, Bayesian, etc., showed similar results.

CONCLUSIONS: Lecanemab demonstrated a decrease in cognitive and functional decline compared to a placebo for the treatment of early-stage AD over an 18-month period. Future meta-analysis studies should also include the safety and tolerability outcomes. Further, longer-term studies are needed to evaluate the effectiveness and safety of lecanemab for the treatment of early-stage AD.