番茄社区

Not all physicians who treat Alzheimer's disease will prescribe the new Alzheimer's drug aducanumab (Aduhelm) -- major hospital systems like the Cleveland Clinic and Mount Sinai in New York City, for example, -- but those who will offer the drug need more information about how to use it, a panel of neuroscientists said.

At the 2021 Alzheimer's Association International Conference (AAIC), a group of physicians and researchers, some of whom were involved in Biogen's aducanumab's trials, issued recommendations for what they consider appropriate use. Their proposal discusses choosing the right patients, managing them, monitoring safety, and communicating with patients and families.

The recommendations emerge amid a flurry of marketing activity designed to encourage people to locate an aducanumab specialist after answering a on a Biogen-sponsored website. The aducanumab campaign includes an on the New York Times' website, a Facebook page, and other promotions.

The treatment suggestions, presented at AAIC and published simultaneously in the (JPAD), aim to give clinicians information about "real-world implementation of this treatment," said author Jeffrey Cummings, MD, ScD, of University of Nevada Las Vegas, who presented the recommendations at AAIC.

A critical part of the guidance is who should not be treated with aducanumab, Cummings emphasized. "How to choose appropriate patients, safely scale up to the full dose, monitor side effects, and assess effectiveness are all described," he said.

A major discussion point in the recommendations -- one not addressed in the aducanumab prescribing instructions -- is proving the presence of amyloid before the drug is administered, Cummings added.

An earlier meeting "highlighted the urgent need for a consensus protocol for clinicians around the country," noted Maria Carrillo, PhD, Alzheimer's Association chief science officer, who was not an author on the paper.

"This is an important starting point, and this JPAD article, and the constructive response to it from the field, will be the basis for additional tools to educate and support clinicians, both primary care physicians and dementia specialists," Carrillo said.

In clinical trials, the most common adverse event, occurring in 41% of people on high-dose aducanumab (the approved maintenance dose), was amyloid-related imaging abnormalities (), including brain edema (ARIA-E) and hemorrhage (ARIA-H), Cummings and colleagues noted.

ARIA-E was seen most commonly in people who were APOE4 gene carriers (43%) and least often in those without APOE4 (20.3%), opening the door to discussions with patients about genotyping, even though aducanumab prescribing information does not require it, the panelists suggested.

"These guidelines have been written despite the current lack of peer-reviewed publications about the phase III pivotal studies so changes may be required once all the data is available in the public domain," observed Serge Gauthier, MD, and Pedro Rosa-Neto, MD, PhD, both of McGill University in Montreal, in a JPAD .

While the recommendations discuss in detail when aducanumab should be started, when to stop treatment isn't clear, they pointed out.

"There has been an effort at defining 'stop rules,' including severe symptoms in the presence of ARIA, inability to reach therapeutic dose, loss of access to clinical and brain imaging monitoring, but the authors stopped short of stating that this treatment should be stopped when reaching a moderate stage of dementia," Gauthier and Rosa-Neto wrote.

"This will likely be a requirement from payers and the next set of use guidelines may operationally define moderate dementia such as global score of 2, lower than 19 at least twice, having lost autonomy on key instrumental activities of daily living," they added.

"Future recommendations could address the need of confirmatory data on clinical efficacy, taking advantage of the FDA requirement for another placebo-controlled study: it is an opportunity to establish if anti-amyloid therapy can be stopped once the amyloid load has been rectified, through a repeat PET amyloid scan after 12 or 18 months, followed by randomization to continuation of aducanumab, to placebo, to an anti-tau drug or a combination of the two drug class," they added.

The panelists' recommendations are a first step, Cummings noted. "We're going to learn so much over the next months and years and these criteria will need revision, for sure," he said.

"But we felt that they were urgently needed for the immediate application, because the drug is here and people need to know how to use it safely. This provides a bridge to the transitions and revisions that will follow."