Effective treatments for Alzheimer disease are needed. The recent approval by the U.S. Food and Drug Administration (FDA) of aducanumab for Alzheimer disease has been controversial, so neurologists, patients and their families are looking for guidance.
The American Academy of Neurology (AAN), the world’s largest association of neurologists with more than 36,000 members, is issuing a position statement for neurologists on decisions with patients and families regarding aducanumab in Alzheimer disease, with recommendations for consent. The statement is published in the November 17, 2021, online issue of Neurology, the medical journal of the American Academy of Neurology, and was developed by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association and Child Neurology Society.
“Aducanumab is not a cure for Alzheimer disease, yet since it has been approved by the FDA, patients are asking their doctors if this is an option for them,” said position statement author Winston Chiong, MD, PhD, of the University of California San Francisco and a member of the AAN’s Ethics, Law, and Humanities Committee. “This is a high-cost drug that was approved by the FDA without convincing evidence of benefits and with known harms, so the purpose of this position statement is to offer ethical guidance on how neurologists can help patients make informed decisions about this treatment.”
The AAN position statement states that aducanumab was approved by the FDA based on two studies that were both stopped prematurely for showing no benefits for study participants. In a later analysis of the data, one of those studies indicated a small benefit, while the other study still showed no benefit. It says that while aducanumab reduces beta-amyloid plaques that are markers of Alzheimer disease in the brain, it remains unclear whether beta-amyloid plaque reduction provides any meaningful benefits to patients.
Ethical guidance in the position statement says it is important to communicate to people that aducanumab does not restore cognitive function. It also says there are insufficient grounds to warrant offering it to people with moderate or advanced dementia, or to those without evidence of beta-amyloid in the brain.
“It is understandable why a new drug for Alzheimer disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” said Orly Avitzur MD MBA FAAN, President of the American Academy of Neurology. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care.”
The position statement says there is a risk of brain inflammation with aducanumab treatment, referred to as amyloid-related imaging abnormalities, which can include brain bleeds. In the studies, aducanumab was associated with brain inflammation and bleeds in one-third of people who received the dose approved by the FDA. The position statement states that neurologists must communicate potential adverse effects and about the need for more frequent monitoring with MRI scans.
Additionally, there was an absence of racial and ethnic diversity in the clinical trials of aducanumab. The statement says this is a significant ethical concern because it deprives people in underserved groups of relevant information about the benefits and harms of the drug for their populations. The position statement says such potential patients should be told about the absence of safety and efficacy data for these groups.
The position statement notes that pricing and coverage of aducanumab may cause financial harm to people taking the drug, depending on how Medicare addresses the individual patient costs. This highly expensive medication has a price tag of $56,000 a year, and that price does not include costs of infusing the drug, repeated imaging and medical management. The position statement says annual costs may exceed $100,000 per year, and Medicare generally covers 80%, so patients and families must be told that the full costs of treatment may not be covered.
While there is hope that aducanumab’s approval will lead to better treatments in the future, the position statement says there are also concerns that its availability may hinder enrollment in clinical trials of more effective interventions.
Source: News Release
American Academy of Neurology
November 17, 2021