Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

• DOI: 10.1001/jamaneurol.2021.4161
• Publication Date: 2021-11-22T16:01:13Z
• Authors: Stephen Salloway; Spyros Chalkias; Frederik Barkhof; Patrick Burkett; Jerome Barakos; Derk Purcell; Joyce Suhy; Fiona Forrestal; Ying Tian; Kimberly Umans; Guanfang Wang; Priya Singhal; Samantha Budd Hae...; Karen Smirnakis
• Keywords: Male; Clinical Trials as Topic; Amyloid beta-Peptides; Antibodies, Monoclonal, Humanized; 16. Peace & justice; Magnetic Resonance Imaging; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Alzheimer Disease; Humans; Female; Original Investigation; Aged

The EMERGE and ENGAGE phase 3 randomized clinical trials of aducanumab provide a robust data set to characterize amyloid-related imaging abnormalities (ARIA) that occur with treatment aducanumab, an amyloid-β (Aβ)-targeting monoclonal antibody, in patients mild cognitive impairment due Alzheimer disease or dementia. To describe the radiographic characteristics ARIA occurred ENGAGE. Secondary analysis from trials, which were 2 double-blind, placebo-controlled, parallel-group, compared low-dose high-dose placebo among participants at 348 sites across 20 countries. Enrollment August 2015 July 2018, terminated early (March 21, 2019) based on futility analysis. combined studies consisted total 3285 who received 1 more doses (n = 1087) 2198; 2752 person-years exposure) during placebo-controlled period. Primary analyses performed November 2019 2020, additional through 2021. Participants randomly assigned 1:1:1 intravenous once every 4 weeks. Dose titration was used as risk-minimization strategy. Brain magnetic resonance monitor for ARIA; associated symptoms reported adverse events. Of included participants, mean (SD) age 70.4 (7.45) years; 1706 (52%) female, 2661 (81%) had disease, 1777 (54%) symptomatic medications disease. A 764 709 categorized withdrawn before study completion, most often owing termination by sponsor. Unless otherwise specified, all results represent 10-mg/kg group. During period, 425 1029 (41.3%) experienced ARIA, serious cases occurring 14 (1.4%). ARIA-edema (ARIA-E) common event (362 [35.2%]), 263 initial events (72.7%) within first 8 aducanumab; 94 (26.0%) exhibited symptoms. Common 103 ARIA-E ARIA-H headache (48 [46.6%]), confusion (15 [14.6%]), dizziness (11 [10.7%]), nausea (8 [7.8%]). Incidence highest aducanumab-treated apolipoprotein E ε4 allele carriers. Most (479 488 [98.2%]) those resolved radiographically; 404 (82.8%) 16 In group, 29 1076 (2.7%) (apolipoprotein carriers: 742 [2.2%]; noncarriers, 13 334 [3.9%]). ARIA-microhemorrhage ARIA-superficial siderosis 197 (19.1%) 151 (14.7%), respectively. this integrated safety ENGAGE, group ARIA-E, 362 (35.2%) least postbaseline MRI scan, experiencing symptom headache. ClinicalTrials.gov Identifiers: NCT02484547, NCT02477800.