#AAN2022 – MRI Protocol to Monitor for ARIA With Aduhelm’s Use Detailed
A standardized MRI protocol to screen for brain imaging abnormalities in people with Alzheimer’s who are being treated with Aduhelm in a large observational study was described in a presentation at the 2022 American Academy of Neurology (AAN) annual meeting.
“Consistency in MRI acquisition is important for efficient and treatment and to overcome [variation] in the generation of real-world evidence,” Tammie Benzinger, MD, PhD, a professor of radiology and neurological surgery at Washington University, said in making the presentation, part of the April meeting’s virtual portion.
“This proposed [protocol] will facilitate monitoring and assessment of [imaging abnormalities] with aducanumab treatment in real-world clinical practice, harmonize the collection of longitudinal data in the real world and inform the aducanumab benefit-risk profile, and lay a foundation for overcoming the existing [variation] of data collection in clinical practice,” Benzinger said.
Her talk was titled, “Defining a Standardized MRI Acquisition Protocol to Be Proposed to ICARE AD Sites for ARIA Monitoring.”
Aduhelm (aducanumab), by Biogen and Eisai, is an antibody-based therapy designed to clear amyloid plaques — the atypical protein clumps characteristic of Alzheimer’s — from the brain. Aduhelm has been shown to lower amyloid levels in clinical trials; however, two large Phase 3 trials found inconsistent results as to whether it could slow cognitive decline.
Based on the early data of amyloid clearance, the U.S. Food and Drug Administration (FDA) approved Aduhelm last year to treat early Alzheimer’s through its accelerated approval pathway.
The initial FDA approval sparked controversy, and access to Aduhelm remains a hotly contested issue. Most recently in the U.S., a decision that Medicare will only cover the therapy for patients in clinical trials has drawn outrage. Meanwhile, Biogen announced that it would no longer be seeking approval of Aduhelm in the European Union after regulatory agencies indicated that available data were not enough to support approval.
In addition to controversies surrounding its efficacy, Aduhelm’s safety has raised concerns. In particular, the medication can cause swelling or bleeding in the brain, a condition referred to as ARIA, which was reported in over 40% of Aduhelm-treated participants in large Phase 3 trials.
“ARIA, or amyloid-related imaging abnormalities, represent a spectrum of imaging findings detected on brain MRI, and are associated with the use of amyloid-targeting monoclonal antibodies including aducanumab,” Benzinger said.
ARIA does not usually cause overt symptoms, but it can lead to symptoms like headache, confusion, dizziness, and nausea. In rare instances, severe reactions like seizures and pronounced bleeding have been reported in patients who develop ARIA while on Aduhelm.
Biogen is sponsoring an observational study called ICARE AD-US (NCT05097131) to collect long-term data on the efficacy and safety of Aduhelm in approximately 6,000 people with Alzheimer’s.
During this trial, in line with FDA guidelines, participants will undergo MRI scans to check for ARIA and to evaluate other changes, like brain atrophy or shrinkage.
Scans are scheduled for the trial’s start (a baseline measure), and again after the seventh treatment infusion (at about six months) and the twelfth infusion (at about 10 months). Scans also will be conducted if clinically indicated.
To detect ARIA and other changes on MRI scans, it is important to have a clear baseline scan against which to make comparisons. It is also critical that all scans be done using a similar setup, so that comparisons can be made easily across scans.
“The current state is that MRIs are typically included in the diagnostic workup of patients for dementia, but we don’t necessarily acquire them in a standardized method in clinical practices,” Benzinger said.
“This consistency, though, is going to be really important both for routine care and research in this patient population. Detecting the change over time, that [swelling or bleeding] associated with ARIA, is really facilitated by having a prior scan that’s comparable with similar parameters,” she added.
In addition to being important in the clinic, Benzinger noted that better standardization will also make it easier to do research, since it will be easier to make comparisons.
MRI works by using powerful magnets and radio waves to detect water molecules within the body. The protocol that will be used in ICARE AD includes four different sequences (combinations of settings to take different types of images): a 3D T2-weighted FLAIR, a 2D T2-weighted gradient-recalled echo, diffusion-weighted imaging, and a 3D T1-weighted gradient-recalled echo.
Each sequence is particularly suited for detecting specific abnormalities. For example, FLAIR is especially useful in identifying brain swelling, while T2-weighted gradient-recalled echo is well-suited to identifying bleeding in the brain. In total, this protocol takes about 20 minutes.
Benzinger noted that this proposed and standardized MRI protocol will facilitate the monitoring and assessment of ARIA with Aduhelm treatment in real-world clinical practice, while harmonizing the collection of data needed to better understand the treatment’s benefits and risks.
Note: The Alzheimer’s News Today team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting.
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