Two studies: another amyloid-directed therapy (crenezumab) does not improve cognition in early Alzheimer disease

Reference

Ostrowitzki S, Bittner T, Sink KM, et al. Evaluating the safety and efficacy of crenezumab vs placebo in adults with early Alzheimer disease: two phase 3 randomized placebo-controlled trials. JAMA Neurol Nov 1 2022;79(11):1113-1121.

Synopsis

These authors report the findings of 2 separate multinational randomized trials (CREAD and CREAD2), each of which randomized adults with prodromal or mild Alzheimer disease to receive monthly infusions of 60 mg/kg crenezumab (n = 811) or placebo (n = 808) for up to 100 weeks. The participants had to have an increased beta-amyloid burden (confirmed by cerebrospinal fluid analysis or amyloid-specific positron emission tomography), a Mini-Mental State Examination (MMSE) score of 22 or higher, and lower scores on other measures of cognition. After 2 years of follow-up, there was no difference in the degree of change in measures of cognition between groups. The overall rate of adverse events was similar (13% and 18%) for each group in both studies. In other studies, 35% of patients taking aducanumab experienced amyloid-related imaging abnormalities. These abnormalities were found in only 3 participants taking crenezumab, all of whom experienced resolution in 4 weeks.