Newly approved drugs treating Alzheimer’s disease (AD) including monoclonal antibodies to remove amyloid-β plaques in the brain are giving new and better treatment options to patients suffering from the disease. Now, the American Academy of Neurology (AAN) has provided new guidance for neurologists to discuss early AD options with patients and their caregivers, via an “Emerging Issues in Neurology” article published this week in the journal Neurology. Emerging Issues in Neurology articles are published to provide updated guidance on issues that have immediate implications for patient care, though the evidence base is still developing.
“Neurologists care for millions of people with Alzheimer’s disease and many people with early forms of dementia are eager to learn if these new therapies could help them,” said AAN president Carlayne E. Jackson, MD. “To help neurologists provide the highest quality care, experts with the American Academy of Neurology have summarized the available evidence on anti-amyloid monoclonal antibodies so that neurologists, patients, and their caregivers can make informed decisions together about possible treatment with these therapies.”
While AAN notes that the published article in not meant to be a formal clinical practice guideline, it is nonetheless intended to provide the most up-to-date information on three monoclonal antibodies that have been approved for the treatment of AD: lecanemab, aducanumab, and donanemab.
Vijay K. Ramanan, MD, PhD, of the Mayo Clinic in Rochester, MN, the author of the article notes that new data on lecanemab and other monoclonal antibodies that target amyloid-β proteins make them very likely to be included in the treatment regimens provided by neurologists for their patients. “While the formal evidence base is still evolving,” he noted, “this article was created with expert consensus until there is enough evidence on these therapies to inform evidence-based recommendations.”
Of the three monoclonal antibodies discussed in the article, only two have been approved by the FDA—aducanumab received accelerated approval in June, 2021 and lecanemab was approved earlier this month. Donenemab is expected to receive approval from the agency later this year.
The focus of the article is to highlight which patients are eligible to receive the treatments. In the cases of lecanemab, it is intended for the treatment of patients with early symptomatic forms of AD—mild cognitive impairment or mild dementia due to AD.
It also provides important information for patients who should not receive these drugs, based on either specific genetic risk factors, or those who have a history of certain kinds of strokes. These patients have a heightened risk of developing a serious side effect called ARIA (amyloid-related imaging abnormalities), which is characterized by swelling and bleeding in the brain that could result in death. In addition, patients taking certain anticoagulants may also not be eligible for these treatments.
The incidence of ARIA can run as high as 40 percent of treated patients in the early approved monoclonal antibodies for AD treatment and three patient deaths have been linked to lecanemab—at least two of the people who died were given anticoagulants while on the AD treatment.
The article further notes that while these therapies’ removal of the amyloid-β slows disease progression, they are not a cure for AD and also points out that the reduction in cognitive decline rates seen over 18 months may not be apparent to those taking the drugs. The authors also highlight that in clinical studies to date of these drugs, Black and Hispanic populations have been underrepresented and advocates that future studies include these populations. This is especially important for Black and Hispanic patients who have shown a higher incidence rate of dementia than found within the white population.
“There is much optimism that anti-amyloid monoclonal antibodies may facilitate slowing of the disease process in some people with Alzheimer’s disease,” concluded Ramanan. “Additional research is needed to further determine who may be most likely to benefit from these therapies, as well as to find ways to improve outcomes for people using them and enable future advances in this new era of Alzheimer’s disease care.”