Abstract Details

Title Clinical Correlates of Amyloid-Related Imaging Abnormalities (ARIA) in Phase 3 Studies of Bapineuzumab in Alzheimer's Disease (AD)

Topic Aging and Dementia

Presentation(s) S44 - (-)

Poster/Presentation
Number 002

Objective

Background ARIA have been reported in multiple trials with anti-amyloid treatments for AD, and include ARIA-E, characterized by effusion or edema seen on FLAIR sequences, and ARIA-H, characterized by hemosiderin deposition see on gradient echo sequences on brain MRI.

Design/Methods APOE ?4 carriers (n=1121; 0.5mg/kg bapineuzumab IV vs. placebo) and non-carriers (n=1331; 0.5; 1.0; or 2.0mg/kg vs. placebo) with mild to moderate AD (MMSE 16-26) received up to 6 infusions of bapineuzumab or placebo over 18 months. ARIA were monitored by MRI at baseline and after each infusion via centralized neuroradiological reads. Clinical (ADAS-Cog, DAD, MMSE) and ARIA-E-related symptoms were assessed by the site investigators.

Results ARIA-E were observed in 0.8% of placebo and 15.8% of bapineuzumab-treated subjects overall. Risk factors for ARIA-E were dose, ?4 allele, female gender, and baseline ARIA-H, but not age or disease severity. Symptoms associated with ARIA-E (eg. headache, confusion, and gait abnormalities) occurred in 2.5% of treated subjects overall, but increased to 7.8% in the 2.0mg/kg group leading to early termination of the high dose arm. Most episodes of ARIA-E occurred prior to the 3rd infusion, without a clear regional predilection. 15% of subjects had a recurrence if dosing was re-initiated after ARIA-E resolved, but remained asymptomatic. There was no difference in the rate of decline on ADAS-Cog, MMSE or DAD observed in ARIA cases compared with non-ARIA bapineuzumab-treated patients.

Conclusions These results confirm risk factors for ARIA observed in Phase 2 studies, and the relationship between ARIA-H and ARIA-E. There is a spectrum of clinical symptomatology associated with ARIA, but no evidence of deleterious effects on long-term clinical outcomes.

Authors/Disclosures
Reisa A. Sperling, MD (Brigham and Women'S Hospital) PRESENTER	Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nervgen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oligomerix. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vaxxinity. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Sperling has received research support from Eli Lilly. The institution of Dr. Sperling has received research support from Eisai. The institution of Dr. Sperling has received research support from NIH.
Stephen P. Salloway, MD, MS (Brown Medical School)	Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lilly. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NovoNordisk. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prothena. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurophet. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kisbee. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CognitionRX. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Icometrix. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck.
Christopher van Dyck, MD (Yale School of Medicine)	Christopher van Dyck, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Christopher van Dyck, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. An immediate family member of Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supurnus. An immediate family member of Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Polaris Management Partners. The institution of Christopher van Dyck, MD has received research support from Roche/Genentech. The institution of Christopher van Dyck, MD has received research support from Eli Lilly. The institution of Christopher van Dyck, MD has received research support from Biogen. The institution of Christopher van Dyck, MD has received research support from Biohaven. The institution of Christopher van Dyck, MD has received research support from Eisai. The institution of Christopher van Dyck, MD has received research support from UCB. The institution of Christopher van Dyck, MD has received research support from Cerevel. The institution of Christopher van Dyck, MD has received research support from Janssen.
H. R. Brashear, MD, FAAN (UVA)	No disclosure on file
Nzeera Ketter, MD (Janssen AI)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Michael H. Arrighi, PhD	No disclosure on file
	No disclosure on file
	No disclosure on file

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