New ‘Real World’ Data on Lecanemab Side Effects

Patients with early Alzheimer’s disease (AD) who initiated lecanemab treatment at a specialty memory clinic showed an expected and manageable side-effect profile, new research showed.

“The findings are very reassuring,” Barbara Joy Snider, MD, PhD, professor of neurology, and director of the Memory Diagnostic Center and Knight ADRC Clinical Trials Unit, Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News.

“We found similar rates of side effects in our patient population as were found in the phase 3 studies of lecanemab. Clinical trial volunteer participants tend to be very healthy, so it is not always a given that side effects will be similar in the clinical population, especially in older adults,” Snider explained.

The study was published online on May 12 in JAMA Neurology.

Real World Data

Lecanemab was the first disease-modifying treatment for AD to receive traditional approval from the US Food and Drug Administration (FDA) in July 2023.

However, side effects, including brain swelling and bleeding, which emerged during clinical trials, left some patients and clinicians hesitant to initiate treatment in appropriate patients.

In this real-world analysis, Snider and colleagues took a look back at 234 patients with early symptomatic AD who initiated lecanemab infusions (10 mg/kg intravenous every 2 weeks) in the memory clinic at WashU Medicine over 14 months. Infusion-related reactions occurred in 87 (37%) study participants and were typically mild.

During an average treatment period of 6.5 months, amyloid-related imaging abnormalities (ARIA) were observed in 42 of 194 patients (22%) who received at least four lecanemab infusions and underwent at least one monitoring MRI scan. 

Overall, 29 (15%) patients developed ARIA with edema/effusion, with or without ARIA with hemorrhage/hemosiderin deposition (ARIA-H) and 13 (6.7%) developed isolated ARIA-H.

The majority of ARIA was asymptomatic and radiographically mild and most patients who developed ARIA stayed on treatment. Eleven patients (5.7%) developed symptomatic ARIA; only two patients (1.0%) had clinically severe ARIA. No deaths or microhemorrhages were observed.

“Importantly,” wrote the investigators, patients with mild dementia at baseline (Clinical Dementia Rating [CDR], 1) had a 15-fold higher rate of symptomatic ARIA than patients with mild cognitive impairment or very mild dementia (CDR, 0.5) at baseline (27% vs 1.8%, P < .001).

“We do not know for sure why people with very mild dementia had fewer side effects than people with mild dementia,” Snider told Medscape Medical News.

“Some findings published based on the clinical trials have shown that people with very mild dementia likely get more benefit from these medications, so this emphasizes the importance of diagnosing Alzheimer’s disease when symptoms are very mild. We have a discussion with each patient and their family about the potential risks and benefits of these medications, so this will be part of that discussion,” Snider said.

“We need to gather more information and follow more patients, not only at our site but more broadly through efforts like ALZ-NET [Alzheimer’s Network for Treatment and Diagnostics] to better understand what factors affect the risks and benefits of these medications,” Snider added.

Summing up, Snider said this real-world analysis showed that “recently approved antibodies against amyloid can be used in an outpatient clinical practice, side effects are as expected and can be managed, and only 1%-2% of patients had clinically concerning side effects.”

‘Valuable’ Evidence

Commenting on this study for Medscape Medical News, Ozama Ismail, PhD, director of scientific programs at Alzheimer’s Association, said the findings of this study “support using approved amyloid-targeting treatments in clinical practice.”

Ismail, who wasn’t involved in the study, said this research contributes “valuable evidence” about the side effects of lecanemab and their management and the findings “align with what was seen during clinical trials.”

“That said, this is just one demonstration of how these treatments are being effectively implemented, administered, and managed within a regional population. Every clinic may have a different perspective and will be serving a different patient population,” Ismail cautioned.

He noted that new FDA-approved treatments offer “real hope for people living with early Alzheimer’s, and they are redefining how Alzheimer’s is addressed. Understanding how these therapies work in real-world settings is essential to improving treatment for everyone — this requires robust data collection beyond controlled clinical trials,” Ismail said.

He also noted that Washington University Memory Diagnostic Center, where this work was done, is part of the ALZ-NET — a nationwide network where healthcare providers collect real-world data from patients who are being evaluated for treatment or are receiving treatment with new FDA-approved AD therapies. ALZ-NET now has more than 2000 patients enrolled in nearly 100 locations across the United States.

The study had no commercial funding. Snider reported receiving advisory board fees and grants from Eisai and Eli Lilly outside the submitted work. A complete list of author disclosures is available with the original article. Ismail had no relevant disclosures.