The Future of Amyloid-fighting Drugs Alzheimer’s Disease and Radiology

In the next few years, expect amyloid-fighting drugs to treat Alzheimer’s disease to be an emerging category of more commonly-used monoclonal antibodies. Researchers, led by Petrice Cogswell, MD, PhD, of the Mayo Clinic, recommend that both neuroradiologists and general radiologists become familiar with the treatment-related side effects caused by amyloid-related imaging abnormalities (ARIAs). The researchers’ white paper was published in the August edition of the American Journal of Neuroradiology.

Lead researcher, Petrice Cogswell, observes that while the efficacy of the newly-released drug, aducanumab, doesn’t have sufficient evidence for CMS to make national coverage determinations, its introduction has hastened the development of amyloid-busters in the pipeline. The team observed, “Given the large number of AD therapeutic candidates, implementation of treatment and monitoring may greatly increase neuroradiology practice volumes.”

Brain abnormalities may appear on MRI examinations in patients receiving amyloid-fighting drugs. These amyloid-related imaging abnormalities tend to occur as one of two types.

• ARIA-E – demonstrating edema or effusion
• ARIA-H – hemosiderosis (iron buildup) or hemorrhage

The researchers recommend that neuroradiologists and radiology generalists become familiar with how this new class of drugs works on Alzheimer’s patients and how the brains of patients treated with amyloid-fighting drugs look on MRI scans. Their suggestions include:

1. Develop knowledge of the pitfalls and challenges of interpreting ARIAs.
2. Select appropriate imaging protocols.
3. Standardize imaging protocols and develop reporting templates to enhance ARIA detection and help confirm accurate and timely communication with referring physicians and ensure optimal patient care.

Dr. Cogswell, MD, PhD, and her research team used the remainder of their white paper to provide a primer on ARIA.

• The acronym was first used in 2010 by the Alzheimer’s Association Research Roundtable — research was already underway in anti-amyloid trials, and trials were revealing amyloid-related imaging abnormalities.
• Baseline imaging should include the number and location of existing microhemorrhages and superficial siderosis must be tabulated on the baseline examination.
• Reimbursement status remains uncertain, “including the presence and extent of insurance coverage, the results of an anticipated Phase IV confirmatory study required by the FDA, multiple stakeholder preparedness across a wide range of clinical practices and other factors.”
• ARIAs occur with amyloid deposition in vessel walls and may damage vascular integrity, lessen drainage in the vascular wall, or produce microhemorrhages.
• Patient selection is critical — Patients with MR imaging–unsafe devices or other MR imaging contraindications (e.g., metallic foreign body in the eye) would not be able to be imaged. Patients with claustrophobia, unable to undergo MR imaging without anesthesia, may be considered ineligible for treatment with amyloid-fighting drugs.
• Asymptomatic patients are typical — most ARIAs are detected on routine surveillance MR imaging examinations. Symptoms include headaches, visual changes, or confusion if the patient is symptomatic.

Cogswell and her colleagues end their study with guidance for the future, “Monoclonal antibody therapies for AD require both baseline pretreatment brain MR imaging and frequent monitoring MR imaging examinations for the detection of potential subclinical adverse events that may require dose adjustment.”

“Because these new AD therapies are disease-modifying, rather than treating symptoms,” the team commented, “current neurology practice operations and infrastructure may need to rapidly evolve to accommodate emerging therapeutics that have very different profiles (relating to adverse effects, financial and nonfinancial costs, test and visit types, and frequencies for treatment initiation and monitoring) from existing options.”