The safety ( n?=?3285) contains all participants who received at least 1 dose of study treatment (placebo or aducanumab) during the placebo-controlled period

The safety ( n?=?3285) contains all participants who received at least 1 dose of study treatment (placebo or aducanumab) during the placebo-controlled period. GUID:?810EEE9B-1CC2-470A-90CE-4686C5B3EF91 Key Points Question What are the characteristics of amyloid-related imaging abnormalities (ARIA) during aducanumab treatment in individuals with early Alzheimer disease? Findings In an integrated security data set of 2 phase 3 clinical trials (EMERGE and ENGAGE) including 3285 participants, 425 patients (41.3%) in the combined 10 mg/kg aducanumab group (n?=?1029) experienced ARIA; ARIA-edema occurred in 362 patients (35.2%), and 94 of these patients (26.0%) experienced associated symptoms (eg, headache, confusion, dizziness, and nausea). ARIA-microhemorrhage and ARIACsuperficial siderosis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively. Meaning Amyloid-related imaging abnormalities occurred in approximately 40% of participants in the phase 3 studies of aducanumab, and approximately one-quarter of these patients experienced symptoms. Abstract Importance The EMERGE and ENGAGE phase 3 randomized clinical trials of aducanumab provide a strong data set to characterize amyloid-related imaging abnormalities (ARIA) that occur with treatment with aducanumab, an amyloid- (A)Ctargeting monoclonal antibody, in patients with moderate cognitive impairment due to Alzheimer disease or Sutezolid moderate Alzheimer disease dementia. Objective To describe the radiographic and clinical characteristics of ARIA that occurred in EMERGE and ENGAGE. Design, Setting, and Participants Secondary analysis of data from your EMERGE and ENGAGE trials, which were 2 double-blind, placebo-controlled, parallel-group, phase 3 randomized clinical trials that compared low-dose and high-dose aducanumab treatment with placebo among participants at 348 sites across 20 countries. Enrollment occurred from August 2015 to July 2018, and the trials were terminated early (March 21, 2019) based on a futility analysis. The combined studies consisted of a total of 3285 participants with Alzheimer disease who received 1 or more doses of placebo (n?=?1087) or aducanumab (n?=?2198; 2752 total person-years of exposure) during the placebo-controlled period. Main data analyses were performed from November 2019 to July 2020, with additional analyses performed through July 2021. Interventions Participants were randomly assigned 1:1:1 to high-dose or low-dose intravenous aducanumab or placebo once every 4 weeks. Dose titration was used as a risk-minimization strategy. Main Outcomes and Steps Brain magnetic resonance imaging was used to monitor patients for ARIA; associated symptoms were reported as adverse events. Results Of 3285 included participants, the mean (SD) age was 70.4 (7.45) years; Rabbit polyclonal to ADORA1 1706 participants (52%) were female, 2661 (81%) experienced moderate cognitive impairment due to Alzheimer disease, and 1777 (54%) used symptomatic medications for Alzheimer disease. A total of 764 participants from EMERGE and 709 participants from ENGAGE were categorized as withdrawn before study completion, most often owing to early termination of the study by the sponsor. Sutezolid Unless otherwise specified, all results represent analyses from your 10-mg/kg group. During the placebo-controlled period, 425 of 1029 patients (41.3%) experienced ARIA, with serious cases occurring in 14 patients (1.4%). ARIA-edema (ARIA-E) was the most common adverse event (362 of 1029 [35.2%]), and 263 initial events (72.7%) occurred within the first Sutezolid 8 doses of aducanumab; 94 participants (26.0%) with an event exhibited symptoms. Common associated symptoms among 103 patients with symptomatic ARIA-E or ARIA-H were headache (48 [46.6%]), confusion (15 [14.6%]), dizziness (11 [10.7%]), and nausea (8 [7.8%]). Incidence of ARIA-E was highest in aducanumab-treated participants who were apolipoprotein E 4 allele service providers. Most events (479 of 488 [98.2%]) among those with ARIA-E resolved radiographically; 404 of 488 (82.8%) resolved within 16 weeks. In the placebo group, 29 of 1076 participants (2.7%) had ARIA-E (apolipoprotein E 4 service providers: 16 of 742 [2.2%]; noncarriers, 13 of 334 [3.9%]). ARIA-microhemorrhage and ARIACsuperficial siderosis occurred in 197 participants (19.1%) and 151 participants (14.7%), respectively. Conclusions and Relevance In this integrated security data set from EMERGE and ENGAGE, the most common adverse event in the 10-mg/kg group was ARIA-E, which occurred in 362.