CEREBROSPINAL FLUID BIOMARKER CONCORDANCE WITH AMYLOID PET IN EMERGE/ENGAGE, PHASE 3 STUDIES OF ADUCANUMAB IN PATIENTS WITH EARLY ALZHEIMER’S DISEASE
- Laura Nisenbaum, United States of America
Abstract
Aims
To assess the use of cerebrospinal fluid (CSF) biomarkers as a valid alternative to positron emission tomography (PET) for amyloid confirmation by conducting a concordance analysis using data from EMERGE (NCT02484547) and ENGAGE (NCT02477800).
Methods
EMERGE and ENGAGE were randomized, double-blind, placebo-controlled, global Phase 3 studies of aducanumab. Participants were 50-85 years old and met clinical criteria for mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease dementia, with a baseline Mini-Mental State Examination score of 24-30 (inclusive) and a CDR global score of 0.5. All enrolled participants had amyloid pathology detected by amyloid PET (visual read) during screening. Participants received an intravenous injection of high-dose aducanumab, low-dose aducanumab, or placebo, randomized 1:1:1, monthly for 18 months. Concordance between CSF biomarkers (amyloid beta [1-42], amyloid beta [1-40], phosphorylated tau [181], total tau, and applicable CSF biomarker ratios; Lumipulse® G immunoassay) and amyloid PET at screening was examined. Positive percent agreement (sensitivity), negative percent agreement (specificity), and overall percent agreement (OPA) using the cutoff value maximizing the Youden J index per biomarker or ratio were determined.
Results
A total of 350 participants (n=308 positive; n=42 negative) provided CSF samples at screening and were included in the analysis. For the CSF Abeta42/Abeta40 ratio, the observed sensitivity of 94%, specificity of 88%, and OPA of 94% in EMERGE and ENGAGE were equivalent to approved PET tracers (sensitivity, 88%-98%; specificity, 80%-95%).
Conclusions
These analyses demonstrate robust concordance between CSF biomarkers and PET amyloid results in EMERGE and ENGAGE.