Does crenezumab improve measures of cognition in adults with Alzheimer disease?
These studies provide additional evidence of the inability of amyloid-directed therapies to improve outcomes in adults with mild Alzheimer disease. A recent study reports that lecanemab slows the rate of cognitive loss as measured by various scales. However, improvement in clinically relevant outcomes have not yet been reported. 1b
Randomized controlled trial (double-blinded)
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.
Henry C. Barry, MD, MS
Michigan State University
East Lansing, MI