Abstract Details

Title Considerations for the Real-World Management of ARIA From the Aducanumab Phase 3 Studies EMERGE and ENGAGE

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 014

Objective To describe the characteristics of amyloid-related imaging abnormalities (ARIA) that occurred in Phase 3 studies EMERGE (NCT02484547) and ENGAGE (NCT02477800) and to inform effective ARIA monitoring and management in real-world clinical practice.

Background ARIA are a spectrum of imaging findings detected on brain magnetic resonance imaging (MRI) and are associated with the investigational use of amyloid-targeting monoclonal antibodies, including aducanumab, in patients with Alzheimer’s disease.

Design/Methods ARIA risk minimization included dose titration, routine brain MRI monitoring, ad hoc MRI testing as clinically indicated, and in patients who developed ARIA, possible dose suspension or permanent discontinuation. The criteria for dose suspension or discontinuation were based on the radiographic severity of ARIA and presentation of clinical symptoms. Monthly follow-up MRIs were conducted to document radiographic resolution of ARIA-edema (ARIA-E) or stabilization of ARIA-hemorrhage (ARIA-H), which refers to brain microhemorrhages and localized superficial siderosis.

Results A pooled EMERGE and ENGAGE safety data set (N = 2192) consisted of 1105 participants in the aducanumab 10 mg/kg group and 1087 participants in the placebo group. In the 10 mg/kg aducanumab group with ≥1 postbaseline MRI, ARIA-E was the most common adverse event (35%) and occurred more frequently in apolipoprotein ε4 carriers than noncarriers (42% vs 20%, respectively). ARIA-E typically occurred within the first 8 doses of aducanumab treatment and were transient and mostly asymptomatic (76%). Radiographic severity of ARIA-E was characterized as mild (30%), moderate (58%), or severe (13%). The most common symptom of ARIA was headache (13%). For events of radiographically severe ARIA-H microhemorrhage and superficial siderosis, 83% and 92%, respectively, were concurrent with ARIA-E. There were no fatal events due to ARIA.

Conclusions ARIA are mostly asymptomatic; evidence supports the use of routine brain MRI in patients treated with aducanumab to monitor for events in clinical practice.

Authors/Disclosures
Richard W. Hughes, MBBS (Biogen) PRESENTER	Dr. Hughes has received personal compensation for serving as an employee of Biogen. Dr. Hughes has stock in Biogen.
	No disclosure on file
Spyridon Chalkias, MD (Biogen)	Dr. Chalkias has received personal compensation for serving as an employee of Biogen.
	No disclosure on file
Carmen Castrillo-Viguera	Dr. Castrillo-Viguera has received personal compensation for serving as an employee of Biogen. Dr. Castrillo-Viguera has received stock or an ownership interest from Biogen.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Karen Smirnakis	No disclosure on file
Samantha Budd Haeberlein	Samantha Budd Haeberlein has received personal compensation for serving as an employee of Biogen. An immediate family member of Samantha Budd Haeberlein has received personal compensation for serving as an employee of Alkermes. Samantha Budd Haeberlein has received stock or an ownership interest from Biogen.

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