• 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).”

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 American Cancer Society. They attach to an antigen – molecules that trigger an immune response.

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.

“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.”

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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