What are the pros and cons of using Leqembi (lecanemab) in patients with early symptomatic Alzheimer's disease?

From the Guidelines

Leqembi (lecanemab) is a valuable treatment option for patients with early symptomatic Alzheimer's disease, offering a modest but significant slowing of cognitive decline, and its use should be considered in eligible patients after careful evaluation of its benefits and risks. This monoclonal antibody targets amyloid beta plaques in the brain, with clinical trials showing a measurable reduction in amyloid plaques and slowing of cognitive and functional decline, potentially extending patients' independence and quality of life 1. The main benefits of Leqembi include its ability to slow disease progression, which can lead to improved outcomes in terms of morbidity, mortality, and quality of life. However, Leqembi carries significant risks, most notably ARIA (amyloid-related imaging abnormalities) which includes brain swelling and microhemorrhages occurring in about 21% of treated patients, as well as other common side effects such as infusion reactions and headaches 1.

Key Considerations

• The medication is contraindicated in patients on anticoagulants or with significant cerebrovascular disease due to increased bleeding risk.
• Treatment requires regular MRI monitoring, especially in the first few months, and costs approximately $26,500 annually before insurance.
• Patients should understand that Leqembi does not reverse existing damage or cure Alzheimer's but rather slows progression, making early diagnosis and treatment initiation crucial for maximizing benefit.
• The decision to use Leqembi should involve thorough discussion of these factors with patients and caregivers, considering the individual's health status, risk factors, and personal preferences.

Benefits and Risks

• Benefits: slowing of cognitive decline, reduction in amyloid plaques, potential extension of patients' independence and quality of life.
• Risks: ARIA, infusion reactions, headaches, increased bleeding risk in patients on anticoagulants or with significant cerebrovascular disease.
• The use of blood-based biomarkers, such as the Aβ42/40 ratio, phosphorylated tau (p-tau), and neurofilament light-chain (NfL), may help identify patients who are more likely to benefit from Leqembi treatment, and standardization of collection, processing, and storage procedures for these biomarkers is crucial for their effective adoption in clinical and research-based settings 1.

Clinical Implications

• Leqembi should be considered as a treatment option for patients with early symptomatic Alzheimer's disease who have confirmed amyloid pathology and are at risk of rapid cognitive decline.
• Patients should be closely monitored for signs of ARIA and other side effects, and treatment should be adjusted accordingly.
• The use of Leqembi in clinical practice should be guided by evidence-based guidelines and recommendations, taking into account the individual patient's needs and circumstances.

From the FDA Drug Label

LEQEMBI is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E), which can be observed on MRI as brain edema or sulcal effusions, and ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis ARIA can occur spontaneously in patients with Alzheimer’s disease, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy, such as pretreatment microhemorrhage or superficial siderosis. Consider the benefit of LEQEMBI for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with LEQEMBI. Incidence of ARIA Symptomatic ARIA occurred in 3% (29/898) of patients treated with LEQEMBI in Study 2 The risk of ARIA, including symptomatic and serious ARIA, is increased in apolipoprotein E ε4 (ApoE ε4) homozygotes.

The pros of using Leqembi (lecanemab) in patients with early symptomatic Alzheimer's disease include:

• Treatment of Alzheimer’s disease
• Initiation of treatment in patients with mild cognitive impairment or mild dementia stage of disease

The cons of using Leqembi (lecanemab) in patients with early symptomatic Alzheimer's disease include:

• Risk of amyloid related imaging abnormalities (ARIA)
• Increased risk of ARIA in apolipoprotein E ε4 (ApoE ε4) homozygotes
• Risk of intracerebral hemorrhages greater than 1 cm in diameter
• Potential for serious and life-threatening events, including seizure and status epilepticus
• Potential for fatal events

The potential benefits of using Leqembi (lecanemab) in patients with early symptomatic Alzheimer's disease include:

• Slowing down the progression of Alzheimer’s disease
• Improvement in cognitive function

The potential risks of using Leqembi (lecanemab) in patients with early symptomatic Alzheimer's disease include:

• ARIA
• Intracerebral hemorrhages
• Serious and life-threatening events
• Fatal events
• Increased risk of ARIA in ApoE ε4 homozygotes 2, 2 It is essential to weigh the potential benefits and risks of Leqembi (lecanemab) and consider the individual patient's risk factors, such as ApoE ε4 carrier status, before initiating treatment 2.

From the Research

Pros of Leqembi (Lecanemab)

• Leqembi has been shown to reduce amyloid plaque load in the brains of Alzheimer's disease patients 3, 4
• It has been approved for the treatment of early Alzheimer's disease (mild cognitive impairment or mild dementia stage of Alzheimer's disease) in several countries, including the United States and Japan 5, 4
• Clinical trials have demonstrated the efficacy and safety of lecanemab in reducing cognitive decline and amyloid burden in early Alzheimer's disease patients 3, 6
• Leqembi has been found to result in moderately less decline on measures of cognition and function than placebo at 18 months 6

Cons of Leqembi (Lecanemab)

• Adverse events, such as amyloid-related imaging abnormalities (ARIA) and infusion reactions, have been reported in patients receiving lecanemab 5, 3, 6
• ARIA can be asymptomatic, but some cases can be serious or even fatal 5
• Microhemorrhages and rare macrohemorrhages may occur in patients receiving lecanemab, and anticoagulation increases the risk of hemorrhage 5
• Patients who are apolipoprotein E ε4 (APOE4) gene carriers, especially APOE4 homozygotes, are at higher risk for ARIA 5
• Some studies have raised concerns about the therapeutic value of lecanemab, particularly in women and APOE4 carriers 7

Potential Benefits of Leqembi (Lecanemab)

• Leqembi may slow cognitive decline in early Alzheimer's disease patients, which could improve their quality of life and functional abilities 3, 6
• Reduction of amyloid plaque load in the brain may have a positive impact on the progression of Alzheimer's disease 3, 4
• Leqembi may be a valuable treatment option for patients with early Alzheimer's disease who have confirmed brain amyloid pathology 5

Potential Risks of Leqembi (Lecanemab)

• Adverse events, such as ARIA and infusion reactions, may occur in patients receiving lecanemab, which could impact their safety and well-being 5, 3, 6
• The long-term efficacy and safety of lecanemab are not yet fully understood, and longer trials are needed to determine its effects on Alzheimer's disease progression 6
• Leqembi may not be effective in all patient populations, such as women and APOE4 carriers, which could limit its therapeutic value 7