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Am Fam Physician. 2022;106(4):462-463

Clinical Question

Is aducanumab (Aduhelm) safe and effective for the treatment of mild cognitive impairment or mild Alzheimer disease?

Bottom Line

This drug was approved by the U.S. Food and Drug Administration (FDA) after its advisory panel voted 10 to 1 against approval, with three members resigning in protest after the FDA decision became public. The drug costs $56,000 per year, which does not include the cost of regular magnetic resonance imaging, physician fees, and the management of complications. This drug has no meaningful impact on symptoms. (Level of Evidence = 1b−)


A report was published on two trials that compared aducanumab with placebo for mild cognitive impairment or mild Alzheimer disease. The studies were the basis for the FDA's approval of the drug over the strong objections of its advisory panel. The EMERGE (n = 1,643) and ENGAGE (n = 1,653) trials identified adults with mild Alzheimer disease or mild cognitive impairment, and evidence of amyloid deposition on positron emission tomography scan. The trials included patients with a Mini-Mental State Examination (MMSE) score between 24 and 30 (30 = normal) and a Clinical Dementia Rating Scale score of 0.5. Patients with evidence of intracranial pathology, including microhemorrhages, hemorrhages, and infarcts, were excluded. Approximately one-fourth of screened patients met these criteria. Patients in each study were randomized to receive placebo, low-dose aducanumab, or high-dose aducanumab, with the dose differing according to the presence or absence of apolipoprotein E4. The trials were halted early for futility, with slightly more than one-half of patients completing the full 75-week follow-up. The authors argue that the trials should not have been stopped, and they presented the data for those patients who completed the full study period. In the report, the results are given for all patients receiving at least one dose of the study drug. The authors found that aducanumab successfully reduced amyloid deposition. Although there were small and sometimes statistically significant changes in the MMSE, Clinical Dementia Rating Scale, and Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-COG) scores, none came close to exceeding the minimum clinically important difference. This is the minimum the score would have to improve before a patient or caregiver is likely to notice improvement.

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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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