Treating early Alzheimer's disease patients with lecanemab (Leqembi) was feasible and most patients tolerated the drug well, a retrospective study at one specialty memory clinic showed.
Infusion-related reactions occurred in 37% of 234 Alzheimer's patients treated with lecanemab and typically were mild, according to Suzanne Schindler, MD, PhD, of Washington University School of Medicine in St. Louis, and co-authors.
Amyloid-related imaging abnormalities (ARIA) emerged in 42 of 194 people (22%) who received at least four lecanemab infusions and had at least one MRI, the researchers reported in JAMA Neurology.
Overall, 29 people (15%) had ARIA with brain edema or effusion (ARIA-E) -- with or without ARIA with brain hemorrhage or hemosiderin deposition (ARIA-H), including microhemorrhages and superficial siderosis -- and 13 people had isolated ARIA-H (6.7%).
Most ARIA cases were asymptomatic (74%) and radiographically mild (62%). Eleven patients (5.7%) developed symptomatic ARIA; two (1.0%) were patients with clinically severe ARIA symptoms. No patients developed a macrohemorrhage or died.
Patients with mild dementia at baseline had a 15-fold higher rate of symptomatic ARIA compared with those with mild cognitive impairment or very mild dementia (27% vs 1.8%, P<0.001), Schindler and colleagues noted.
"Most patients on lecanemab tolerate the drug well," Schindler said in a statement. "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."
Lecanemab, approved by the FDA in 2023 to treat early Alzheimer's disease, is a monoclonal antibody that binds with high affinity to amyloid-beta soluble protofibrils. In the phase III CLARITY-AD clinical trial, 12.6% of lecanemab-treated participants had ARIA-E and 17.3% had ARIA-H. Recent data from the open-label extension study updated those figures and reported that three deaths concurrent with ARIA or intracerebral hemorrhage occurred.
Lecanemab and donanemab (Kisunla), another anti-amyloid treatment, won approval based on evidence that they slowed cognitive decline in people with early symptomatic Alzheimer's, defined as mild cognitive impairment, very mild dementia, or mild dementia due to Alzheimer's disease.
Both drugs carry a boxed warning for ARIA, especially for people who are APOE4 homozygotes. A recent analysis suggested lecanemab and donanemab may extend independent living by 10 to 13 months for some Alzheimer's patients.
Schindler and colleagues conducted a retrospective analysis of 234 consecutive patients who started lecanemab treatment between August 2023 and October 2024 at the outpatient specialty memory clinic at Washington University. The 234 patients accounted for 5.9% of 3,938 memory clinic patients seen during that period.
Patients were treated with 10 mg/kg lecanemab intravenously every 2 weeks. Mean baseline age was 74 and 50% of patients were female; nearly all (98%) treated patients were white.
Compared with the CLARITY-AD study, a lower percentage of lecanemab-treated patients in the Washington University study were APOE4 homozygotes (8.5% vs 16%, P=0.004). Nine Washington University patients (3.8%) were receiving anticoagulant medications and 83 patients (35%) were taking antiplatelet agents including aspirin and/or clopidogrel (Plavix) at baseline.
Infusion-related reactions, which were mostly mild or moderate, were more frequent in the Washington University study than in CLARITY-AD (37% vs 26%, P=0.002). In mid-July 2024, the Washington University treatment protocol was changed to include pretreatment with an antihistamine and acetaminophen before initial infusions; the rate of infusion-related reactions dropped to 27% after this change.
No patients with fewer than four infusions developed symptomatic ARIA or had ARIA findings on urgent MRI scans. Patients at risk for ARIA were treated for an average of 6.5 months.
"Of the 194 patients at risk for ARIA during the study period, 44 patients (23%) had at least one microhemorrhage and/or superficial siderosis before lecanemab treatment was initiated," Schindler and co-authors noted.
"Of note, patients with a greater burden of microhemorrhages and/or superficial siderosis were excluded from treatment and, therefore, 23% is an underestimate of the prevalence of these findings in patients with early symptomatic Alzheimer's disease," the researchers pointed out. "This suggests that a proportion of ARIA-H that develops during the course of treatment is unrelated to anti-amyloid antibody treatment."
Overall, 23 of 234 (9.8%) patients in the study withdrew from lecanemab treatment for various reasons, including 10 (4.3%) people who withdrew due to ARIA.
A study limitation and important concern was the very low diversity of patients being treated with lecanemab, Schindler and colleagues said. While this study showed how anti-amyloid antibodies can be provided in a specialty memory clinic with rich resources, these treatments could be used in other clinics using a variety of strategies, they added.
Disclosures
Funding for this study included support from the Barbara Morriss trust.
Schindler reported personal fees from Eisai, Eli Lilly, and Novo Nordisk outside the submitted work. Her employer, Washington University, has a stake in C2N Diagnostics. Co-authors reported multiple relationships with industry and other agencies.
Primary Source
JAMA Neurology
Source Reference: Paczynski M, et al "Lecanemab treatment in a specialty memory clinic" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.1232.
https://www.medpagetoday.com/neurology/alzheimersdisease/115551
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