Aducanumab Appropriate Use for Alzheimer Disease Treatment Recommendations Updated
An update to appropriate clinical use of aducanumab (Aduhelm; Biogen, Cambridge, MA and Eisai, Woodcliff Lake, NJ) for treatment of Alzheimer disease (AD) was published in the Journal of Prevention of Alzheimer's Disease and presented in a panel discussion at the Alzheimer Association International Conference 2022 (AAIC2022) in San Diego, CA and online.
The update is based on evidence from real-world use of aducanumab and intended to improve risk mitigation, safety monitoring, patient selection, and shared decision-making. Recommendation updates include genetic testing for the apolipoprotein E ε4 (APOE ε4) allele, MRI monitoring before and during treatment, and screening for comorbid conditions that may make the adverse event amyloid-related imaging abnormalities (ARIA) more likely. Additionally, considerations for treatment of ARIA and discontinuation of aducanumab when ARIA is recurrent are provided.
Regarding patient selection, it is recommended that aducanumab be used only in people, age 50 to 85, with mild cognitive impairment due to AD or mild AD. Patients should have confirmed brain amyloid pathology on positron emission tomography (PET) or a profile of cerebrospinal fluid (CSF) biomarkers consistent with amyloid pathology using amyloid (Aβ42), total-tau (t-tau), and phosphorylated-tau (p-tau).
Candidates for aducanumab therapy should have no other neurologic disorders, no autoimmune/inflammatory comorbidities or bleeding disorders (including the use of anticoagulants), and no history of seizures. All other chronic conditions should be stable, including cardiovascular disease. Use in individuals over age 85 could be considered if all other selection criteria are met. Concomitant use of memantine or cholinesterase inhibitors is considered acceptable.
Laboratory studies prior to treatment for risk assessment and patient selection should include vitamin B12, thyroid stimulating hormone (TSH), metabolic panel and liver function tests (LFT), complete blood count (CBC), comprehensive clotting studies and platelet count, erythrocyte sedimentaton rate (ESR) and C-reactive protein (CRP).
As noted, APOE ε4 genotyping should also be done to assess for risk of ARIA. In clinical trials, 66% of participants who had 2 copies of APOE ε4 and 36% of participants with 1 copy of APOE ε4 had ARIA.
Neuroimaging with MRI should occur before treatment initiation to rule out risk factors for ARIA, including acute or subacute macrohemorrhage, more than 4 microhemorrhages, lacunar or cortical infarction larger than 1.5 cm, more than 1 area of superficial siderosis, or extensive white matter disease indicative of ischemic injury. During titration of aducanumab, MRI should be performed before the 5th, 7th, 9th, and 12th infusions to improve detection of ARIA, which can be asymptomatic. It is strongly recommended that MRI be done with the same equipment throughout treatment as much as possible.
Most cases of ARIA are transient and treatable. The recommendations provide guidance for additional MRI monitoring when symptoms of ARIA occur as well as guidance for treatment of ARIA and when ARIA warrants discontinuation of treatment with aducanumab. Preparedness of hospital systems and emergency department protocols are also discussed
Finally, the panel emphasized the importance of individualized risk assessment based on clinical evaluation, patient education and counseling, and shared decision-making. It was also noted that equitable access to treatment is needed.