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Am Fam Physician. 2024;109(5):478-479

Clinical Question

Does treatment with monoclonal antibody therapy that targets amyloid improve patient outcomes?

Bottom Line

Amyloid-targeting antibodies for the treatment of Alzheimer disease have failed to demonstrate clinically meaningful benefits. They are associated with concerning risks of harm, most notably cerebral hemorrhage identified on imaging studies (number needed to harm [NNH] = 13). The balance of risk vs. benefit demonstrated so far does not justify the use of these costly drugs (more than $20,000 annually). (Level of Evidence = 1a)


The authors of the systematic review and meta-analysis of randomized controlled trials sought to determine whether monoclonal antibody medications that target amyloid for the treatment of Alzheimer disease provide clinically meaningful, patient-oriented benefits or harms. This is an important question because federal approval of these medications was based on surrogate markers. The authors included 19 studies with 23,202 participants. Inclusion criteria involved the enrollment of adults with cognitive impairment, Alzheimer disease of any severity, or a high risk of Alzheimer disease, and the reporting of an outcome of interest. The authors excluded trials or trial arms that used doses lower than those approved by the U.S. Food and Drug Administration. All studies were industry-funded placebo-controlled trials. Most studies enrolled patients with mild cognitive impairment or mild to moderate Alzheimer disease. Outcomes of interest were well-defined minimum clinically important differences in the results for any of the multiple cognitive scoring tools and potential harms. The drugs used in the trials included in the meta-analysis were solanezumab, aducanumab (Aduhelm), lecanemab (Leqembi), donanemab, and bapineuzumab. Notably, there are no head-to-head trials with other drugs. The summary analysis showed that improvement vs. placebo was small (standardized mean difference = −0.07; 95% CI, −0.10 to 0.04). Although some statistically significant benefits were identified, none were close to reaching a minimum clinically important difference threshold. There was no overall difference between treatment and control groups for all-cause mortality, although bapineuzumab was associated with an increase (relative risk [RR] = 1.76; 95% CI, 1.03 to 3.00; NNH = 102). The harms that were reported most often were amyloid-related imaging abnormalities (ARIA) edema (RR in overall analysis = 10.3; 95% CI, 7.4 to 14.3; NNH = 9), symptomatic ARIA-edema (RR for the three drugs reporting = 24.3; 95% CI, 9.9 to 59.9; NNH = 86), and ARIA-hemorrhage (RR = 1.74; 95% CI, 1.2 to 2.4; NNH = 13).

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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at

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