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Monoclonal antibodies targeting amyloid produce minimal cognitive and functional improvements in Alzheimer’s dementia that do not reach clinical significance, while significantly increasing the risk of ARIA-related harms.
A meta-analysis evaluating the clinical impact of monoclonal antibodies targeting amyloid in Alzheimer’s disease reveals only modest cognitive and functional improvements, accompanied by significant risks.
Mark H Ebell and other researchers systematically reviewed PubMed, Cochrane CENTRAL, 5 clinical trial registries, and reference lists to point out randomized controlled trials comparing anti-amyloid antibodies with placebo. Included studies utilized doses consistent with phase 3 trials or those approved by the U.S. Food and Drug Administration and reported at least 1 clinically meaningful benefit or harm. Data from at least 2 independent researchers were extracted for random-effects meta-analysis. The focus was on alteration in functional and cognitive scales and assessing whether these fulfilled the minimal clinically important difference (MCID).
The analysis incorporated 19 publications encompassing 23,202 volunteers and examined 8 different anti-amyloid antibodies. Results revealed minor improvements over placebo in key measures:
Notably, none of these improvements—including those observed with lecanemab, aducanumab, and donanemab—reached the MCID threshold, suggesting limited clinical relevance. The study also highlighted critical safety concerns. Those treated with anti-amyloid antibodies faced markedly heightened risks of:
These findings indicate that while anti-amyloid therapies may offer slight cognitive and functional benefits, the improvements are minimal and overshadowed by clinically meaningful adverse effects. The authors conclude that current monoclonal antibody treatments for Alzheimer’s dementia offer limited clinical benefit and carry substantial risks, emphasizing the requisition for careful patient selection and ongoing evaluation of safety profiles.
Annals of Family Medicine
Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis
Mark H Ebell et al.
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