Systematic review finds more clinical harm than benefits in Alzheimer’s “treatments” lecanemab, aducanumab, and donanemab
Study questions benefit of new Alzheimer’s drug (UGA Today):
Last summer, the U.S. Food and Drug Administration fully approved the first drug shown to slow the progress of Alzheimer’s. But new research from the University of Georgia suggests that patients and caregivers may not experience any benefit from the drug in their daily lives.
The drug, Leqembi, became eligible for coverage through Medicare, making it more affordable for the millions of Americans in the early stages of the disease. But experts remained skeptical that the drug provided enough benefit to justify the cost and potential harms of the drug.
A new study from UGA’s Mark Ebell systematically reviewed 19 publications with over 23,000 participants that evaluated eight monoclonal antibodies, including Leqembi.
“We focused very clearly on patient-centered outcomes,” said Ebell, who is a physician and professor of epidemiology and biostatistics in UGA’s College of Public Health. “We found that even after 18 to 24 months of treatment, the differences in function and cognition between treated and untreated patients were so small that a patient or their caregiver generally wouldn’t notice the difference,” said Ebell. “For example, the Mini-Mental State test has 30 possible points, but the difference seen in the studies was less than a third of a point. To be noticeable to a patient or their family, that difference would have to be at least 1 to 3 points.”
The study suggests the drug’s hefty cost, time burden, and potential side effects, which include brain swelling and brain bleeds, may not be worth the minimal benefit for most patients … “The potential benefit always has to be weighed against any potential harms,” said Ebell. “And it’s not by any means a clear-cut choice.”
Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis (The Annals of Family Medicine). From the Abstract:
- PURPOSE: We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia.
- METHODS: We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies … Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID).
- RESULTS: We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies … None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema, ARIA-hemorrhage, and symptomatic ARIA-edema.
- CONCLUSIONS: Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
The Study in Context:
- Should doctors prescribe lecanemab (Leqembi) to women? The answer, given available evidence, is probably No
- First, do no harm? Six reasons to approach anti-amyloid drug Aduhelm cautiously, if at all
- Report: 35% of worldwide dementia cases could be prevented by modifying these 9 modifiable risk factors