CHICAGO, Ill. -- By Kim Yun-mi/Korea Biomedical correspondent - Biogen’s Alzheimer’s disease treatment Aduhelm (ingredient: aducanumab) is being used in patient care after obtaining marketing approval in the U.S. earlier this year.
Still, researchers have yet to solve the problem of monitoring and managing amyloid-related imaging abnormalities (ARIA), an adverse reaction of the drug.
Neuroradiology is one of the hottest fields discussed at the Radiological Society of North America’s 107th Scientific Assembly and Annual Meeting (RSNA 2021) in Chicago that runs through Wednesday.
In particular, Alzheimer’s is drawing much attention because Aduhelm targeting amyloid-beta is already used in clinical scenes, and other anti-amyloid candidates with the same action mechanism report ARIA as a common adverse reaction in late-stage clinical trials.
ARIA was reported in 41 percent of Aduhelm-treated patients, but it was not Aduhelm’s specific problem but a common side effect seen in anti-amyloid agents.
Most patients with ARIA are asymptomatic, and doctors should manage and control it through regular monitoring of medical images.
In a phase 3 trial of Aduhelm, 76 percent of patients who reported ARIA did not show any symptoms.
At the radiology forum, experts proposed making a protocol where clinicians identify ARIA, judge the severity, and manage the patient’s status before anti-amyloid drugs become popular in clinical settings.
Professor Tammie S. Benzinger of radiology and neurological surgery at Washington University School of Medicine in St. Louis, who is working on trials of Alzheimer’s treatments being developed by Biogen, Roche, Lilly, J&J, and Eisai, presented the imaging and severity criteria for ARIA based on a clinical trial protocol at RSNA 2021.
In an online session hosted by Biogen on Monday, Benzinger said ARIA had two types.
One is ARIA-E, commonly discovered by FLAIR, one of MRI sequences, and the other is ARIA-H, mainly found by GRE/T2. ARIA-E shows sulcal abnormalities and ARIA-H, hemosiderin deposition, she explained.
She also presented the criteria for the severity of ARIA, used in clinical trials.
In ARIA-E, if there is one legion and less than 5cm, ARIA was deemed “mild”; multiple legions and less than 5cm or one/several legions and between 5 and 10cm, “moderate”; and one/several legions and 10cm or bigger, “severe.”
In ARIA-H, the severity is classified into micro-hemorrhages and superficial siderosis. In the case of micro bleeding, if there are less than four, it is classified as “mild”; five to nine, “moderate”; and more than 10, “severe.” Hemosiderin deposition was classified as “mild” if there was one lesion, “moderate” with two lesions, and “severe” with three or more.
However, Benzinger emphasized that it is essential to distinguish it from other causes of the disease when diagnosing ARIA.
When a new legion was found in the clinical trials, researchers thoroughly reviewed to rule out the possibility of causes of the disease other than ARIA, she said.
Patients suspected of ARIA should go through strict clinical review before the diagnosis, she added.
Benzinger also said that dose increasing and APOE4 gene were risk factors of ARIA and that in ARIA-E, most patients had mild to moderate ARIA and no symptoms.
Most ARIA cases are transient and occur mainly in the early stages of the drug administration, she said.
At a debate that followed, however, experts pointed out the limitations of the proposed protocol.
They questioned whether regular MRI monitoring was possible in reality.
In clinical trials, regular MRI monitoring was performed to verify the drug’s effect and safety.
However, in reality, it is almost impossible for ordinary people to receive MRI scans often.
Experts discussed whether alternatives such as PET could help detect or monitor ARIA, but they said PET was more inaccurate than MRI.
They also questioned whether the proposed ARIA diagnosis and severity criteria could be applied identically to all patients.
Such protocol was carried out in a strictly controlled environment during clinical trials.
However, if patients are suspected of ARIA in real clinical settings, it will not be easy to distinguish it from other disease causes, critics said.
Benzinger admitted the limitations of the protocol, saying that more use of anti-amyloid agents in clinical scenes will lead us to more questions in the future.