Lecanemab's real-world effects in Alzheimer's patients are infrequently observed, according to empirical data.
Alzheimer's disease, a type of dementia, is a challenging disease without a cure as of now. However, recent years have seen the introduction of new medications to alleviate symptoms and slow its progression. One such promising treatment is lecanemab, known as Leqembi in the market.
FDA approved lecanemab in 2023, joining the battle against Alzheimer's disease. This medication is not without its drawbacks, but it can help manage the disease's symptoms and potentially slow down the disease's progression.
Much like any other medicine, lecanemab carries the risk of side effects. While common side effects like headaches, dizziness, muscle aches, and blurred vision are relatively mild, there's a severe side effect to watch out for - amyloid-related imaging abnormalities (ARIA). Signs of ARIA may include swelling or bleeding in the brain.
Back in 2022, researchers conducted the Clarity AD phase 3 clinical trial to examine lecanemab's safety and effectiveness. The study displayed that only around 0.8% of participants faced ARIA-E (edema/effusion), and 0.7% presented ARIA-H (hemorrhage/hemosiderin deposition).
Recent research has reaffirmed the findings from the Clarity AD trial. According to this new study, ARIA instances were uncommon and easy to manage in real-world use of lecanemab for people with early-stage Alzheimer's disease.
Getting to know lecanemab
Lecanemab is essentially a special antibody designed to recognize specific types of amyloid proteins. These proteins can become misshapen in the body and, once they do, they can interfere with brain activity, forming clumps called amyloid plaques. In Alzheimer's disease, amyloid misfolding might be one of the initial steps leading to memory loss and dementia.
The alliance of lecanemab and amyloid plaques
Barbara Joy Snider, MD, PhD, a professor of neurology at WashU Medicine, explained, "Lecanemab, an antibody, is created to target specific proteins in the body. In the case of lecanemab, it recognizes certain types of amyloid proteins. When these proteins become misshapen, they can interfere with brain activity and form clumps called amyloid plaques. This process happens in Alzheimer's disease."
Snider continued, "In a large clinical trial, people who were treated with lecanemab for 18 months revealed approximately 25-30% less decline in their memory and thinking compared to those who didn't get the medication. Imaging studies showed that lecanemab reduced and sometimes cleared the amyloid plaques in the brain."
The occurrence of ARIA in early-stage Alzheimer's patients
In the recent study, 234 patients with early-symptomatic Alzheimer's disease, with an average age around 74, were enrolled to receive lecanemab at the Washington University Memory Diagnostic Center's outpatient specialty memory clinic. The research found that 1.8% of patients at the earliest stage of Alzheimer's disease experienced symptoms of ARIA. In comparison, 27% of patients with mild Alzheimer's disease displayed ARIA symptoms.
Snider emphasized that the early stages of Alzheimer's disease are critical for getting the most benefits from medications like lecanemab and reducing side effects. She stated, "The clinical trial results indicated that people with very mild symptoms are likely to gain more from medications like lecanemab (40-50% slowing of decline instead of 25-30%). This is also the phase when it is most challenging to be certain someone has Alzheimer's disease. Therefore, it is crucial that we continue to work on improving access to diagnosis for people with very mild symptoms."
The researchers noticed that out of the 11 participants who experienced ARIA symptoms, the effects disappeared in a matter of months for most patients, and no fatalities were reported. Snider added, "This is quite similar to what was observed during the clinical trial. This is very reassuring as it suggests that such drugs can be used securely in real-world clinical settings."
Deeper research into ARIA risk
John Dickson, MD, PhD, a neurologist at Massachusetts General Hospital, agreed with the study's findings, stating that ARIA instances, while occurring in patients treated with lecanemab, are generally manageable in specialized treatment programs.
Dickson acknowledged that further research is required to identify patients at an increased risk of ARIA, particularly those with concerning symptoms or radiographic features. "By doing so, we can provide more personalized recommendations for treatments based on each patient's individual risk profile," stated Dickson.
Deciding between lecanemab and other treatments like donanemab could become easier with more research like this.
Weighing benefits against side effects for lecanemab
Manisha Parulekar, MD, FACP, AGSF, CMD, the director of the Division of Geriatrics at Hackensack University Medical Center, addressed the delicate balance between the benefits provided by lecanemab and the potential for severe side effects: "The approval of lecanemab may bring some optimism to Alzheimer's patients, but it requires careful consideration due to the risk of serious side effects that calls for cautious prescribing by physicians."
Patient selection, monitoring, open communication about benefits, and risks are essential to making informed decisions regarding lecanemab use. "Identifying patients who are most likely to gain from lecanemab and least likely to experience severe side effects is crucial," stated Parulekar. "Access to additional safety data and real-world experience will help in this regard."
- Alzheimer's disease, a neurological disorder and a type of dementia, is a challenging medical-condition without a cure as of now, but recent years have seen the introduction of new drugs like lecanemab, a promising treatment for Alzheimer's disease.
- As a special antibody, lecanemab, known as Leqembi in the market, is designed to recognize specific types of amyloid proteins, which can become misshapen and form clumps called amyloid plaques in Alzheimer's disease, interfering with brain activity and potentially leading to memory loss and dementia.
- In a large clinical trial, people who were treated with lecanemab for 18 months showed approximately 25-30% less decline in their memory and thinking compared to those who didn't get the medication, and imaging studies showed that lecanemab reduced and sometimes cleared the amyloid plaques in the brain.
- In the recent study, 1.8% of patients at the earliest stage of Alzheimer's disease experienced symptoms of amyloid-related imaging abnormalities (ARIA), a severe side effect to watch out for with lecanemab use, while 27% of patients with mild Alzheimer's disease displayed ARIA symptoms.
- By conducting deeper research into ARIA risk, it's possible to identify patients at an increased risk of ARIA, enabling more personalized recommendations for treatments, such as lecanemab or other therapies and treatments for neurological disorders, based on each patient's individual risk profile.
