An expert panel has released the first recommendations on the appropriate use of aducanumab (Aduhelm), the controversial anti-amyloid drug that was approved by the US Food and Drug Administration (FDA) in June for adults with early Alzheimer's disease (AD).
"There are incredible gaps between the FDA label and what most of us in the field feel need to happen in terms of detailed guidance on using this drug," panel member Alireza Atri, MD, PhD, director of the Banner Sun Health Research Institute (Banner Health), in Sun City, Arizona, told Medscape Medical News.
"This is a first-in-class drug where the vast majority of clinicians have no experience with it and patients and their caregivers are already asking for it and there are some really important conversations to be had ― not only about who may qualify to begin with and also about potential effectiveness and safety," Atri added.
The aducanumab recommendations were published online July 27 in The Journal of Prevention of Alzheimer's Disease to coincide with their presentation at the Alzheimer's Association International Conference (AAIC) 2021.
A separate article outlining the key recommendations was published in Alzheimer's and Dementia: Translational Research and Clinical Interventions.
The panel recommends that aducanumab only be used for patients with clinical features similar to those of the patients who took part in the clinical trials that led to the drug's approval ― patients with mild cognitive impairment (MCI) due to AD and mild AD dementia who have brain amyloid, as confirmed on amyloid positron-emission tomography (PET) or with cerebrospinal fluid (CSF) findings consistent with AD.
"You're giving a drug that's been approved on accelerated status for lowering amyloid, so amyloid status needs to be verified either by an amyloid PET scan or spinal fluid," said Atri.
The panel also recommends that patients under consideration for aducanumab treatment have no psychiatric problems; that they be medically stable with no cardiovascular or cardiopulmonary conditions; that they are not taking anticoagulants; that they have no organ failure; and that they have no active cancer except for low-grade basal and squamous cell carcinomas. Current treatment with cholinesterase inhibitors and memantine is acceptable.
Atri noted that the prescribing label for the drug provides "broad strokes about titration." The panel recommends that the drug be titrated to the highest dose to maximize opportunity for efficacy.
Monthly infusions should begin with a dose of 1 mg/kg for the first and second infusions. They should be increased to 3 mg/kg for infusions three and four and to 6 mg/kg for the fifth and sixth infusions. The intended dose of 10 mg/kg should be administered on the seventh infusion. The target dose level of 10 mg/kg should then be continued for the foreseeable future, the panel notes.
Safety monitoring is critically important. The panel recommends structured monitoring for amyloid-related imaging abnormalities of the effusion (ARIA-E) or hemorrhagic (ARIA-H) type. Patients should undergo MRI at least 1 year before aducanumab treatment is initiated or at baseline if there are any suggestions of a focal brain event since the last MRI. MRI should again be conducted before the fifth, seventh, and 12th infusions.
The panel says the "best practice" for providing aducanumab therapy is to adopt a patient-centered focus.
"Not a Cure"
"There should be comprehensive discussions and clear communication with the patient and care partner regarding the requirements for therapy, the expected outcome of therapy, potential risks and side effects, and the required safety monitoring, as well as uncertainties regarding individual responses and benefits," said Atri.
"Patients need to know that this is not a cure. It's not going to actually make their cognition better, but by removing amyloid, there is a reasonable chance it's going to slow down clinical decline," he added.
"You could have two identical twins who would qualify and when you have this discussion with them, based on the risk and reward calculus, one may reasonably decide this is not for me, and that's really important," Atri added.
He cautioned that these initial recommendations are "a starting point, not a finishing point," and will be updated as needed.
"This paper takes no stance on advocating for this treatment. But now that it's available, let's put up some guardrails and use it appropriately and safety," Atri said.
"Clinicians are requesting clarity and more specific information about the appropriate use of this new treatment," Rebecca Edelmayer, PhD, senior director of scientific engagement, the Alzheimer's Association, told Medscape Medical News.
These first appropriate-use recommendations are "a first step and will certainly evolve over time as the medication is prescribed," Edelmayer said.
The research had no specific funding. Atri has received honoraria for consulting; participating in independent data safety monitoring boards; providing educational lectures, programs, and materials; or serving on advisory boards for AbbVie, Acadia, Allergan, the Alzheimer's Association, Axovant, AZ Therapies, Biogen, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Lundbeck, Merck, Roche/Genentech, Novo Nordisk, Sunovion, and Suven. Edelmayer has disclosed no relevant financial relationships.
J Prev Alz Dis. Published July 27, 2021. Abstract
Alzheimer's Association International Conference (AAIC) 2021.
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Cite this: First Guidance on Appropriate Use of Controversial Alzheimer's Drug - Medscape - Jul 27, 2021.