Initial experiences with amyloid‐related imaging abnormalities in patients receiving aducanumab following accelerated approval

Abstract

AbstractBackgroundAducanumab is the first approved amyloid‐lowering immunotherapy for Alzheimer’s disease (AD). There is little real‐world data to guide the management of amyloid‐related imaging abnormality (ARIA), a potentially serious side‐effect requiring surveillance with serial magnetic resonance imaging (MRI). The current study seeks to characterize the symptoms, clinical course and management of ARIA in memory clinic patients treated with aducanumab.MethodWe conducted a non‐blinded, observational case series of patients who received aducanumab from June 16, 2021 to August 1, 2022 at the Butler Hospital Memory and Aging Program. Inclusion: (1) Clinical diagnosis of mild cognitive impairment (MCI) or mild dementia due to AD, (2) confirmed amyloid positivity (PET/CSF), and (3) Mini Mental State Exam (MMSE) = 20‐30. Exclusions: (1) MRI with > 4 microhemorrhages, > 1 area of superficial siderosis or significant cerebrovascular disease, (2) MRI contraindication, (3) anticoagulation and (4) unstable medical/psychiatric conditions. Participants received monthly aducanumab infusions, titrated to a dose of 10 mg/kg, with ApoE genotyping and enhanced MRI monitoring adapted from the phase 3 trials. The primary outcome of the study was the identification of ARIA‐E by MRI. Secondary outcomes included severity of ARIA, clinical course, and time to resolution.ResultOut of 24 patients treated with aducanumab, we identified ARIA‐E in 6 patients (25%), all ApoE‐ε4 carriers, and 4 of whom had moderate‐severe radiographic severity. Comorbid ARIA‐H occurred in 3 patients, 1 of whom also had new onset of cerebellar metastatic cancer. Symptomatic ARIA occurred in 3 patients and included headache, confusion, gait instability, and word‐finding difficulties. Treatment was discontinued in 4 cases of moderate‐severe ARIA‐E, temporarily held in 1 moderate/asymptomatic case, and dosed through in 1 mild/asymptomatic case. All cases of ARIA‐E resolved without hospitalization or corticosteroids (mean duration = 3 months, range, 1 ‐ 6 months).ConclusionAdditional amyloid‐lowering antibodies, associated with ARIA, may soon become clinically available. These data support the careful patient selection, ApoE genotyping, MRI surveillance and individualized dosing recommended in the updated FDA prescribing information and Appropriate Use Recommendations.