Alzheimer's: Real-world data shows lecanemab side effects are rare

Medical News Today

16-05-2025

The FDA approved lecanemab for Alzheimer's disease in 2023. Jakob Lagerstedt/Stocksy The medication lecanemab was approved by the U.S. FDA to treat Alzheimer's disease in 2023.
Like all medications, lecanemab comes with the potential for side effects, including amyloid-related imaging abnormalities (ARIA), such as the presence of swelling or bleeding in the brain.
The Clarity AD phase 3 clinical trial, published in 2022, reported very low percentages of participants experiencing ARIA.
A new study reconfirms the Clarity AD findings by reporting that significant adverse events, such as ARIA, were rare and manageable in real-world use of lecanemab for people within the earliest stages of Alzheimer's disease.
While there is currently no cure for a type of dementia called Alzheimer's disease, over the last few years, new medications have been introduced to help manage disease symptoms and slow its progression.
Like all medications, lecanemab has the potential for side effects, including headaches, dizziness, muscle aches, and blurred vision, as well as a very serious side effect known as amyloid-related imaging abnormalities (ARIA), such as the presence of swelling or bleeding in the brain.
In November 2022, scientists published the results of the Clarity AD phase 3 clinical trial aimed at determining the safety and efficacy of lecanemab in people with early Alzheimer's disease. In that study, researchers found 0.8% of participants experienced ARIA-E (edema/effusion) and 0.7% showed signs of ARIA-H (hemorrhage/hemosiderin deposition).
Now, a new study recently published in JAMA Neurology reconfirms the Clarity AD findings by reporting that significant adverse events — such as ARIA — were rare and manageable in 'real-world' use of lecanemab for people with very mild or mild Alzheimer's disease.
For this study, researchers recruited 234 people with early symptomatic Alzheimer's disease, with an average age of about 74, who received lecanemab at the outpatient specialty memory clinic, Washington University Memory Diagnostic Center.
'Lecanemab is an antibody, a kind of protein normally made in your body by your immune system,' Barbara Joy Snider, MD, PhD, a professor of neurology at WashU Medicine and affiliated with the Knight Alzheimer's Disease Research Center, and co-senior author of this study, explained to Medical News Today . 'Antibodies like lecanemab are designed to have specific targets and are manufactured, then administered to patients. Antibodies are used for many different conditions.' Lecanemab and amyloid proteins
'Lecanemab was designed to recognize certain types of amyloid protein . This is a protein that is made in your body and can become misfolded. When this happens, it can interfere with brain activity and can form clumps called amyloid plaques . This is what happens in Alzheimer's disease. Amyloid misfolding is not the only thing that happens in the brain in Alzheimer's disease, but it may be one of the first steps in the disease process that leads to memory loss and dementia.'
— Barbara Joy Snider, MD, PhD
'In a large clinical trial, people who were treated with lecanemab for 18 months had about 25-30% less decline in their memory and thinking than did people who did not get the medication,' Snider said.
'It is important to note that the people treated with lecanemab did have a loss in their memory and thinking, so the drug did not reverse or completely stop the memory loss, but it did significantly slow it down. Imaging studies showed that the lecanemab also reduced and sometimes cleared the amyloid plaques in the brain,' she added.
At the study's conclusion, researchers found that 1.8% of participants at the earliest stage of Alzheimer's disease showed symptoms of ARIA, compared to 27% of participants with mild Alzheimer's disease.
'This finding emphasizes the importance of early diagnosis. The clinical trial results showed that people with very mild symptoms likely benefit more from medications like lecanemab (40-50% slowing of decline instead of 25-30%), so people with very mild symptoms have more benefit and fewer side effects. This is also when it is hardest to be sure someone has Alzheimer's disease, so it is very important that we continue to work to improve access to diagnosis for people with very mild symptoms.'
— Barbara Joy Snider, MD, PhD
Snider and her team also discovered that of the 11 participants who experienced ARIA symptoms, the effects mostly disappeared within a few months, and no patients died.
'This is very similar to what was seen in the clinical trial,' Snider commented. 'This is very reassuring and tells us that these drugs can be used safely in a 'real world' clinic population.'
'We will continue to follow our patients and hope to learn more about side effects of these medications and about how much they slow down memory loss,' she continued. 'We look forward to sharing this information with other providers and to seeing larger studies through groups like Alz-Net. We are encouraged by our experience of providing amyloid-targeting treatments to appropriate patients and we look forward to the next generation of treatments for Alzheimer's disease.'
MNT spoke with John Dickson, MD, PhD, a neurologist at Massachusetts General Hospital, about this study. Dickson commented that the study's findings are generally in line with what he has observed at his center.
'While ARIA does occur in patients treated with lecanemab, it has been manageable in our sub-specialty treatment program,' he explained. 'The risk of ARIA is often the most significant consideration in eligible patients' decisions about whether to pursue treatment with anti-amyloid therapy or not.' Lecanemab or donanemab?
'Further research to identify patients at increased risk for ARIA, especially serious ARIA with concerning symptoms or radiographic features, could help clinicians advise patients with more personalized recommendations regarding treatment based on individual patients' risk profiles. This may help patients make more informed decisions regarding their treatment options. These treatment decisions include whether or not to pursue treatment with anti-amyloid therapy, and if so, whether lecanemab or donanemab would be a better option.'
— John Dickson, MD, PhD
Dickson said that for future research, these findings should be examined in a larger patient sample and that the observation time should be extended.
'In general, the risk of ARIA is highest in the first six months of treatment,' he explained. 'While some of the patients included in this study had more than six months of treatment, some patients were observed for a shorter period of time. Thus, the results of this study may underestimate the number of patients who will develop ARIA from the study population.'
'While the approval of lecanemab offers a glimmer of hope for Alzheimer's patients, the potential for serious side effects makes it a complex decision for prescribing physicians,' Parulekar said. 'Careful patient selection, monitoring, and open communication about the benefits and risks are essential.'
'The benefit offered by lecanemab is a modest slowing of decline, not a cure or a dramatic reversal. It is important to weigh its benefit against the potential for serious side effects for each individual patient. This requires careful consideration of the patient's disease stage, overall health, and other risk factors.'
— Manisha Parulekar, MD, FACP, AGSF, CMD
'Identifying patients who are most likely to benefit from lecanemab and least likely to experience serious side effects is crucial,' Parulekar added. 'Additional safety data and 'real world' experience [are] helpful for this process.'
Alzheimer's / Dementia
Clinical Trials / Drug Trials
Seniors / Aging
Drugs