A novel Alzheimer's therapy approved by the FDA in 2023 has demonstrated a manageable safety profile outside of clinical trials, according to new research from Washington University School of Medicine in St. Louis. The study, published May 12 in JAMA Neurology, found that significant adverse events associated with lecanemab were rare and could be effectively managed in a specialty clinic setting.
Researchers analyzed data from 234 patients with very mild or mild Alzheimer's disease who received lecanemab infusions at WashU Medicine's Memory Diagnostic Center. Only 1% of patients experienced severe side effects requiring hospitalization, consistent with findings from controlled clinical trials.
"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, professor of neurology and co-senior author of the study. "But fear surrounding the drug's potential side effects can lead to treatment delays."
Treatment Benefits and Risk Stratification
Lecanemab, an antibody therapy that clears amyloid plaque proteins from the brain, has been shown to extend independent living by approximately 10 months. The medication is specifically recommended for people in the early stages of Alzheimer's disease.
A key finding from the study was the significant difference in adverse event rates based on disease severity. 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," explained Dr. 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."
Understanding ARIA and Safety Monitoring
Much of the hesitation surrounding lecanemab stems from a side effect known as amyloid-related imaging abnormalities, or ARIA. These abnormalities appear on brain scans and indicate swelling or bleeding, typically affecting only a small area of the brain.
In clinical trials of lecanemab, 12.6% of participants experienced ARIA, with most cases being asymptomatic and resolving without intervention. Approximately 2.8% of treated participants experienced symptoms such as headaches, confusion, nausea, and dizziness. Rare deaths have been linked to lecanemab in an estimated 0.2% of treated patients.
The Memory Diagnostic Center began treating patients with lecanemab in 2023 following FDA approval. Patients receive the medication via infusions every two weeks. As part of standard care, doctors regularly perform sophisticated brain imaging to monitor for potential complications.
Real-World Outcomes
The retrospective analysis found that the extent of side effects in the clinic setting aligned closely with those observed in clinical trials. Most cases of ARIA were asymptomatic and only discovered through routine monitoring scans.
Of the 11 patients who experienced symptoms from ARIA, the effects largely resolved within a few months, and no patients died. The protocol at WashU Medicine includes discontinuing lecanemab in patients with symptomatic ARIA or significant asymptomatic ARIA, with severe cases treated with steroids in the hospital.
"Most patients on lecanemab tolerate the drug well," said Suzanne Schindler, MD, PhD, associate professor of neurology and 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."
Clinical Implications
The findings suggest that specialized memory clinics have the infrastructure and expertise to safely administer lecanemab and manage potential side effects. This could help alleviate concerns among patients and healthcare providers about implementing this treatment option.
The study also reinforces the importance of early diagnosis and treatment of Alzheimer's disease, as patients with very mild symptoms not only showed better tolerance to the medication but are also likely to experience greater clinical benefit.
As more healthcare facilities gain experience with administering lecanemab, these real-world data may help inform treatment decisions and optimize patient selection, potentially expanding access to this disease-modifying therapy for appropriate candidates.
