The Food and Drug Administration’s approval in 2023 of lecanemab — a novel Alzheimer’s therapy shown in clinical trials to modestly slow disease progression — was met with enthusiasm by many in the field as it represented the first medication of its kind able to influence the disease. But side effects — brain swelling and bleeding — emerged during clinical trials that have left some patients and physicians hesitant about the treatment.
Medications can have somewhat different effects once they are released into the real world with broader demographics. Researchers at Washington University School of Medicine in St. Louis set out to study the adverse events associated with lecanemab treatment in their clinic patients and found that significant adverse events were rare and manageable.
Consistent with the results from carefully controlled clinical trials, researchers found that only 1% of patients experienced severe side effects that required hospitalization. Patients in the earliest stage of Alzheimer’s with very mild symptoms experienced the lowest risk of complications, the researchers found, helping to inform patients and clinicians as they navigate discussions about the treatment’s risks.
The retrospective study, published May 12 in JAMA Neurology, focused on 234 patients with very mild or mild Alzheimer’s disease who received lecanemab infusions in the Memory Diagnostic Center at WashU Medicine, a clinic that specializes in treating patients with dementia.
“This new class of medications for early symptomatic Alzheimer’s is the only approved treatment that influences disease progression,” said Barbara Joy Snider, MD, PhD, a professor of neurology and co-senior author on the study. “But fear surrounding the drug’s potential side effects can lead to treatment delays. Our study shows that WashU Medicine’s outpatient clinic has the infrastructure and expertise to safely administer and care for patients on lecanemab, including the few who may experience severe side effects, leading the way for more clinics to safely administer the drug to patients.”
Lecanemab is an antibody therapy that clears amyloid plaque proteins, extending independent living by 10 months, according to a recent study led by WashU Medicine researchers. Because amyloid accumulation is the first step in the disease, doctors recommend the drug for people in the early stage of Alzheimer’s, with very mild or mild symptoms. The researchers found that only 1.8% of patients with very mild Alzheimer’s symptoms developed any adverse symptoms from treatment compared with 27% of patients with mild Alzheimer’s.
“Patients with the very mildest symptoms of Alzheimer’s will likely have the greatest benefit and the least risk of adverse events from treatment,” said Snider, who led clinical trials for lecanemab at WashU Medicine. “Hesitation and avoidance can lead patients to delay treatment, which in turn increase the risk of side effects. We hope the results help reframe the conversations between physicians and patients about the medication’s risks.”
Hesitation around lecanemab stems from a side effect known as amyloid-related imaging abnormalities, or ARIA. The abnormalities, which typically only affect a very small area of the brain, appear on brain scans and indicate swelling or bleeding. In clinical trials of lecanemab, 12.6% of participants experienced ARIA and most cases were asymptomatic and resolved without intervention. A small percentage — approximately 2.8% of participants treated — experienced symptoms such as headaches, confusion, nausea and dizziness. Occasional deaths have been linked to lecanemab in an estimated 0.2% of patients treated.
The Memory Diagnostic Center began treating patients with lecanemab in 2023 after the drug received full FDA approval. Patients receive the medication via infusions every two weeks in infusion centers. As part of each patient's care, WashU Medicine doctors regularly gather sophisticated imaging to monitor the brain, which can detect bleeding and swelling with great sensitivity. Lecanemab is discontinued in patients with symptoms from ARIA or significant ARIA without symptoms, and the rare patients with severe ARIA are treated with steroids in the hospital.
In looking back on their patients’ outcomes, the authors found the extent of side effects aligned with those of the trials — most of the clinic’s cases of ARIA were asymptomatic and only discovered on sensitive brain scans used to monitor brain changes. Of the 11 patients who experienced symptoms from ARIA, the effects largely resolved within a few months and no patients died.
“Most patients on lecanemab tolerate the drug well,” said Suzanne Schindler, MD, PhD, an associate professor of neurology and a co-senior author of the study. “This report may help patients and providers better understand the risks of treatment, which are lower in patients with very mild symptoms of Alzheimer’s.”
Journal
JAMA Neurology
Method of Research
Experimental study
Subject of Research
People
Article Title
Lecanemab treatment in a specialty memory clinic: feasibility and safety
Article Publication Date
12-May-2025
COI Statement
Paczynski M has served as a site sub-investigator for clinical trials sponsored by Eisai and participated in one scientific advisory board for Eisai. The laboratory of Musiek ES has previously received research funding from Eisai for animal studies related to sleep. Holtzman DM co-founded, has equity, receives royalty income based on technology (stable isotope labeling kinetics and blood plasma assay) and is on the scientific advisory board of C2N Diagnostics, which offers the PrecivityAD2 blood test. He is on the scientific advisory boards of Denali, Genentech, Cajal Neuroscience and Switch therapeutics and consults for Asteroid and Pfizer. Bateman RJ has received research funding from Avid Radiopharmaceuticals, Janssen, Roche/Genentech, Eli Lilly, Eisai, Biogen, AbbVie, Bristol Myers Squibb and Novartis. He co-founded C2N Diagnostics, which offers the PrecivityAD2 blood test. Washington University and Bateman RJ have equity ownership interest in C2N Diagnostics and receive income based on technology (stable isotope labeling kinetics, blood plasma assay, and methods of diagnosing AD with phosphorylation changes) licensed by Washington University to C2N Diagnostics. Bateman RJ receives income from C2N Diagnostics for serving on the scientific advisory board. He serves as an unpaid member on scientific advisory boards for Roche and Biogen. Long JM has served as site sub-investigator for clinical trials sponsored by Eisai and Eli Lilly. He has served on an advisory board related to blood-based biomarker testing for Lucent Diagnostics. He has received compensation for participation on a Data Safety Monitoring Board for Noah Pharmaceuticals. Ghoshal N has participated or is currently participating in clinical trials of anti-dementia drugs sponsored by Bristol Myers Squibb, Eli Lilly/Avid Radiopharmaceuticals, Janssen Immunotherapy, Novartis, Pfizer, Wyeth, Roche, Eisai, SNIFF (The Study of Nasal Insulin to Fight Forget-fulness), and the A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial. She serves as a consultant for BCBSA. Carr DB has served as co-principal investigator for clinical trials sponsored by Biogen, Eisai, Eli Lilly and Hoffman La Roche. He has served as a consultant for the Traffic Injury Research Foundation, Medscape and UpToDate. Dow A is a consultant on the Lecanemab Site of Care Strategic Council for Eisai and his consulting fees are donated to the BJC Employee Assistance Fund. Benzinger TLS has received grants or contracts from Siemens paid to her institution and consulting fees from Biogen, Eli Lilly, Eisai, Bristol Myers Squibb, J&J and Merck. She has participated in a Data Safety Monitoring Board or Advisory Board of Siemens. She has received technology transfer and precursors for radiopharmaceuticals from Avid Radiopharmaceuticals/Eli Lilly, LMI, and Lantheus, as well as a scanner loan from Hyperfine to her institution. Schindler SE has served on scientific advisory boards on biomarker testing and clinical care pathways for Eisai and Novo Nordisk and has received speaking fees for presentations on biomarker testing from Eisai, Eli Lilly, and Novo Nordisk. Snider BJ has served as a site principal investigator for clinical trials sponsored by Biogen, Eisai, Eli Lilly, and Hoffman La Roche. She has served on scientific advisory boards on use of anti-amyloid treatments for Biogen, Eisai and Roche.