Aducanumab: A Tentative Position

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Aducanumab’s recent approval by the US Food and Drug Administration (FDA) for Alzheimer disease has been controversial. In response, the American Academy of Neurology (AAN) issued a position statement for mental health professionals, covering decisions with patients and families regarding aducanumab in the treatment of Alzheimer disease, strongly recommending consent.¹

“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 one of the authors, 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.”

The AAN position statement stresses that it is ethically important to communicate that aducanumab does not restore cognitive function. Although 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. Additionally, there are insufficient grounds to warrant offering it to patients 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 notes that there is a risk of amyloid-related imaging abnormalities with aducanumab treatment, including brain bleeds. During research, aducanumab was associated with brain inflammation and bleeds in a third of the individuals who received the FDA-approved dose. Physicians need to communicate potential adverse effects when discussing this treatment option with patients.

Another ethical concern the position statement noted is the absence of racial and ethnic diversity in the clinical trials of aducanumab. Minority populations are thus deprived of relevant information about the benefits and harms of the drug for their specific populations.

Finally, pricing and coverage of aducanumab may cause financial harm to patients receiving the drug, depending on how Medicare decides to address individual patient costs. With a price of $56,000 a year—not including costs of infusing the drug, repeated imaging, and medical management—aducanumab could end up costing patients and families significant amounts annually. The position statement recommends physicians discuss how full costs of treatment may not be covered by Medicare.

Helen Lavretsky, MD, MS, a professor in-residence in the Department of Psychiatry at the University of California, Los Angeles, and Psychiatric Times^TM editorial board member, concurred with the AAN. “I am very much in agreement with the very cautious statement that emphasizes the limited evidence for significant cognitive or functional improvement, the lack of promise to reverse or even slow Alzheimer disease progression, the very high cost of the drug and monitoring protocols, and the exuberant cost of the drug to the Medicare that would triple the cost of AD care, even if only 10% [of individuals] with Alzheimer disease receive the drug, along with the lack of data on long-term safety outcomes warrant a very careful approach and recommendation for the patients and families.”

“The decision should be made by doctors together with patients and [after] full disclosure of incurring costs of treatment, most often not covered by the insurances, that can only offer limited benefits for cognition along with high likelihood of brain inflammation, and complicated protocols for safety monitoring with costly expensive brain scans. The administration of the drug will also require collaborative care model between primary care and geriatric neurology and psychiatry,” said Lavretsky further.

Lavretsky also wished to draw attention to a viewpoint by Salloway and Cummings,² who noted that the approval and implementation of aducanumab is justified and will open a new era in the treatment of Alzheimer disease.

The full statement is published in the online issue of Neurology.

References

1. Chiong W, Tolchin BD, Bonnie RJ, et al. Decisions with patients and families regarding aducanumab in Alzheimer disease, with recommendations for consent: AAN position statement. Neurology. November 17, 2021. Accessed November 22, 2021. https://n.neurology.org/content/early/2021/11/17/WNL.0000000000013053

2. Salloway S, Cummings J. Aducanumab, amyloid lowering, and slowing of Alzheimer disease.Neurology. 2021;97(11):543-544.