Real-World Characterization of Amyloid-Related Imaging Abnormalities (ARIA) in Lecanemab Treatment at an Academic Health System

BackgroundThe benefits of amyloid-{beta} monoclonal antibodies for Alzheimers disease are tempered by the risk of amyloid-related imaging abnormalities (ARIA). Detailed real-world characterization of ARIA, including incidence, timing, radiologic severity and localization, natural history, and risk factors, is essential to optimize treatment safety. This study provides a comprehensive description of ARIA in a large real-world cohort of patients receiving lecanemab. MethodsIn this retrospective cohort study from the Mass General Brigham Alzheimers Therapeutic Program, we analyzed data from 468 patients with early Alzheimers disease who were at least 90 days from their first lecanemab infusion, including those whose treatment was modified or discontinued. ARIA was monitored using a standardized MRI protocol. High-dimensional analysis of baseline clinical, laboratory, and biomarker variables was performed using univariate correlations and Cox proportional hazards models with data-driven cutpoints. FindingsThe overall incidence of any ARIA was 25.2%, with ARIA-H occurring in 22.4% of patients and ARIA-E in 12.2%. Symptoms developed in 4.5% of all patients. Both subtypes demonstrated significant occipital involvement, with ARIA-H showing additional frontotemporal predominance. ARIA-H was typically mild and persistent with rare radiologic resolution, whereas ARIA-E was transient, resolving with a mean time to resolution of 75.6 days. Key baseline predictors of ARIA-H included CSF A{beta}42 [≤]683.8 pg/mL (HR 6.39), [≥]1 microhemorrhage (HR 2.55), and at least one APOE {varepsilon}4 allele (HR 1.77). ARIA-E was predicted by diastolic blood pressure >75 mmHg (HR 3.12), serum chloride >105 mmol/L (HR 2.79), at least one APOE {varepsilon}4 allele (HR 2.51), and serum sodium >141 mmol/L (HR 1.70). ARIA-Mixed was associated with elevated serum chloride >105 mmol/L (HR 3.92), at least one APOE {varepsilon}4 allele (HR 2.87), and diastolic blood pressure >75 mmHg (HR 2.60). InterpretationThis comprehensive real-world characterization of ARIA, together with the identification of novel modifiable risk factors for ARIA-E, including elevated diastolic blood pressure and high-normal serum electrolytes, enables personalized risk assessment and tailored monitoring, thereby advancing the safe implementation of disease-modifying Alzheimers therapies. FundingFunding for this project was provided by the Mass General Neuroscience Transformative Scholar Award.