Abstract Details

Title State of the Art Central Review of Brain Magnetic Resonance Imaging (MRI) Scans in Phase 3 Clinical Trials of Intravenous Bapineuzumab

Topic Aging and Dementia

Presentation(s) P06 - (-)

Poster/Presentation
Number 035

Objective

Background BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (with hemosiderin deposition). As ascertainment of ARIA has improved dramatically since initiation of these studies, central review of all safety monitoring MRI scans was conducted retrospectively.

Design/Methods DESIGN/METHODS: A total of 15,713 MRI scans obtained during Study 301 in APOE*E4 non carriers (1,331 patients) and 302 in APOE*E4 carriers (1,121 patients) were reviewed after the subject had completed trial participation. Five pairs of neuroradiologists, blinded to treatment assignment, were trained to recognize and quantify the extent and location of ARIA. Each neuroradiologist pair individually reviewed a patient's series of MRI scans using a sequential, locked process. The differences in the final results were adjudicated by reader pair consensus.

Results RESULTS: ARIA-E was identified in 243 subjects including 76 additional subjects not identified during the study. Compared to the safety monitoring MRI, ARIA-E was not identified in 1 patient or confirmed in 4 patients in this post hoc review. Treatment emergent ARIA-E was higher in bapineuzumab treated APOE*E4 carriers (active 21.2%; placebo 1.1%) than in non carriers (active 7.1 %, 0.6%). The overall agreement for the 5 pairs of neuroradiologists had a kappa 0.69 for the presence of ARIA-H <10mm and 0.73 for the presence of ARIA-E.

Conclusions CONCLUSIONS: ARIA was detected more often in MRI scans when neuroradiologists were trained and the results adjudicated. Additional data will be presented regarding the location and severity of ARIA-E, the quantity and location of ARIA-H and correlations between ARIA-E and ARIA-H in addition to other radiologically significant findings such as age-related white matter disease.

Authors/Disclosures
Nzeera Ketter, MD (Janssen AI) PRESENTER	No disclosure on file
H. R. Brashear, MD, FAAN (UVA)	No disclosure on file
	No disclosure on file
	No disclosure on file
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
Achim Gass, MD (U Hospital Mannheim, U of Heidelberg)	Dr. Gass has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Alasdair Coles, MD, PhD (University of Cambridge)	Dr. Coles has nothing to disclose.
	No disclosure on file
	No disclosure on file

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