- Researchers
are reporting that the risk of using monoclonal antibody treatments to
treat Alzheimer’s disease might outweigh the benefits they provide.
- Scientists have developed monoclonal antibodies
for people with Alzheimer’s based on the theory that amyloid deposits
might contribute to the disease and that these treatments can clear the
deposits.
- Although the researchers noted improvements in
laboratory tests with these treatments, they said there were only minimal
improvements in people and the potential risks outweighed those
improvements.
The risks of monoclonal antibody treatments for people
with Alzheimer’s disease might outweigh the
benefits, according to a meta-analysis completed by researchers
from the American Academy of Family Physicians.
The researchers located 19 publications that evaluated
the effects of eight monoclonal antibodies with 23,202 participants.
They reported that neither the overall nor day-to-day
functioning of people using the treatments showed evidence of improvement
beyond minimal differences.
“This is a very important article because as new treatments for Alzheimer’s disease
emerge, it is vital for patients and their families to understand whether these
treatments apply to them and what their potential benefits and harms are,” said Dr. Mike Gorenchtein, a
physician at Northwell Health specializing in geriatric medicine who was not
involved in the study.
“This meta-analysis looked at eight different
monoclonal antibodies, which work slightly differently from each other and have
demonstrated variable levels of beneficial responses and side effects,”
Gorenchtein told Medical News Today. “The U.S. Food and Drug
Administration (FDA) has approved the use of lecanemab and aducanumab for Alzheimer’s disease,
preferably for patients with mild cognitive impairment (memory decline
with overall functional independence) and early
dementia (more severe memory deficits with functional
dependence).”
What are
monoclonal antibodies?
Monoclonal antibodies
were developed based on the theory that amyloid deposits are part of the causal
pathway in the development of Alzheimer’s
disease.
These drugs are meant to reduce the amyloid deposits.
Antibodies are proteins created to help
fight disease, according to the
When scientists identify the antigen that is
responsible for Alzheimer’s or other diseases, they can redesign antibodies
that target a certain antigen. Once they attach to the antigen, they can help
the immune system attack other cells containing the antigen.
Potential
risks with monoclonal antibodies
“The most common side
effects of monoclonal antibody treatment are amyloid-related imaging
abnormalities (ARIA), of which brain edema and intracerebral
bleeding are the most serious and life-threatening,”
Gorenchtein said. “The incidence of these side effects differs among the
monoclonal antibodies.”
The researchers reported that monoclonal antibodies
can cause cerebral edema and hemorrhage.
These health hazards were tied to specific drugs.
- The
drug
bapineuzumab was associated with a significant increase in mortality. - The
drugs lecanemab, aducanumab, and donanemab were
associated with ARIA-H, cerebral microhemorrhages, minor bleeding in the
brain, and hemosiderosis.
- ARIA-E,
with symptoms such as headache, confusion, vomiting, and visual or gait disturbances,
was significantly increased in those who received lecanemab and donanemab.
The FDA approved these drugs based primarily on improvements
to laboratory measurements such as medical imaging and biomarkers.
However, researchers said the monoclonal antibodies
provided only small benefits on cognitive and
functional abilities, far below what would be considered clinically
significant.
“Based on this research, I would not recommend
monoclonal antibodies be used to treat Alzheimer’s,” Dr. Mark
Ebell, a professor at the University of Georgia and one of the lead
authors of the study, told Medical News Today. “But I do think it is important
that patients and their caregivers are fully informed of the limited benefits,
significant potential harms, and high cost of these medications. It should be
clear that on average, after 18 to 24 months, most patients and their
caregivers would not notice the benefit.”
Gorenchtein disagrees. He said the treatments can be
helpful sometimes. In the appropriate circumstances, he said patients should be
informed about all types of available treatments.
“I would, therefore, discuss these therapy options
with patients whose cognitive impairment is mild, who are
largely functionally independent, and who can actively participate in the
treatment decision-making process,” he said. “Strong social support, realistic expectations,
adherence to the treatment schedules, and close monitoring are equally
imperative. I would not recommend these treatments to patients with advanced cognitive decline and who are
largely functionally dependent on their caregivers.”
However, he points out that the study could have
provided additional information.
“Currently, monoclonal antibody treatment is largely
recommended for patients with mild cognitive impairment or early stages of
Alzheimer’s disease for optimal benefit,” Gorenchtein said. “It may have added
further value if this meta-analysis focused specifically on these patients for greater
relevance to the clinically treated population.”
Research and
current treatments for Alzheimer’s disease
The researchers said
that previous reviews of monoclonal antibody treatments had significant flaws.
For example, they noted that some reviews included
phase 1 and 2 trials that used different doses from those in later trials. The
researchers from the earlier reviews also did not interpret the findings using
minimal clinically significant differences in patient outcomes.
“There are several medications that may help slow the rate of
cognitive decline. Three of these medications are cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) – they are often the first line
for patients with mild cognitive impairment and mild to moderate dementia,” the
researchers wrote.
“Since there is currently no cure for Alzheimer’s
disease, management is largely through a combination of patient and caregiver
education, supportive services, behavioral and lifestyle modifications, and
medications to improve the quality of life,” Gorenchtein said. “In some people,
they can cause side effects such as nausea, vomiting, diarrhea, weight loss,
and slow heart rate.”
“Memantine is
another medication that works through a different mechanism and can be added to
cholinesterase inhibitors in cases of more advanced dementia or if patients
cannot tolerate cholinesterase inhibitors,” Gorenchtein added. “It can cause
dizziness and worsening confusion in some people.”
“Treatment of the behavioral problems in Alzheimer’s
disease, which are often more troubling than the cognitive symptoms, is usually
a combination of behavioral therapy, family and caregiver education, and
medications,” he said. “Non-pharmacological approach is preferred to limit pill
burden and medication side effects. If patients develop severe behavioral
symptoms such as depression, multiple classes of anti-depressant
medications such as selective serotonin reuptake inhibitors (SSRIs)
can be used.”
“In advanced dementia stages, patients can develop agitations and delusions, which are treated with behavioral
modifications, and in certain cases, medications for the delusions,”
Gorenchtein added.
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