From the Guidelines
Leqembi (lecanemab) treatment for early Alzheimer's disease (AD) requires careful management of amyloid-related imaging abnormalities (ARIA), which can cause brain swelling or microhemorrhages in approximately 13% of patients, as reported in studies such as 1 and 1.
Key Considerations
- Treatment involves biweekly intravenous infusions of 10 mg/kg, with patients requiring baseline MRI screening and APOE genotyping before starting therapy, as suggested by 1 and 1.
- Management includes regular MRI monitoring for ARIA, with a focus on detecting edema (ARIA-E) and microhemorrhages (ARIA-H), as discussed in 1 and 1.
- If ARIA occurs, treatment may need to be temporarily suspended until symptoms resolve, as recommended by 1 and 1.
- Prognosis with Leqembi shows modest benefits, with clinical trials demonstrating approximately 27% slowing of cognitive decline over 18 months compared to placebo, as reported in 1 and 1.
Risk Factors and Monitoring
- The presence of Apolipoprotein E ε4 allele is a significant risk factor for the development of ARIA-E, as found in studies such as 1 and 1.
- Regular MRI monitoring is essential to detect ARIA, with a focus on frequent scanning in early clinical development, as suggested by 1 and 1.
- The timing of MR scans in relation to dosing should be considered, taking into account pharmacodynamic effects and pharmacokinetic levels, as discussed in 1 and 1.
Comprehensive Care
- Treatment requires specialized centers with MRI capabilities and should be integrated with comprehensive care, including cognitive stimulation, lifestyle modifications, and caregiver support, as recommended by 1 and 1.
- Patients should be counseled about realistic expectations, as the medication slows progression rather than reverses symptoms, as noted in 1 and 1.
From the FDA Drug Label
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) and ARIA with hemosiderin deposition (ARIA-H) ARIA is usually asymptomatic, although serious and life-threatening events can occur. ARIA can be fatal. Serious intracerebral hemorrhages greater than 1 cm have occurred in patients treated with this class of medications. ARIA-E can cause focal neurologic deficits that can mimic ischemic stroke. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. Recommendations for dosing in patients with ARIA-E depend on clinical symptoms and radiographic severity. Recommendations for dosing in patients with ARIA-H depend on the type of ARIA-H and radiographic severity. Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E. Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI.
Lequembi Associated ARIA Treatment, Prognosis, and Management:
- Treatment:
- Clinical evaluation and MRI scanning if symptoms suggestive of ARIA occur
- Dosing recommendations depend on clinical symptoms and radiographic severity of ARIA-E and ARIA-H
- Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E
- Prognosis:
- ARIA can be fatal
- Serious and life-threatening events can occur
- Serious intracerebral hemorrhages greater than 1 cm have occurred in patients treated with this class of medications
- Management:
- Baseline brain MRI and periodic monitoring with MRI are recommended
- Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI
- Consider pre-medication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids for infusion-related reactions 2 2 2
From the Research
Leqembi Associated ARIA Treatment, Prognosis, and Management
- Leqembi (lecenemab) is approved for the treatment of Alzheimer's disease (AD) and has been associated with amyloid-related imaging abnormalities (ARIA) 3, 4, 5, 6.
- ARIA can be asymptomatic or symptomatic, and its incidence is higher in apolipoprotein E4 (APOE4) homozygous carriers 3, 5.
- The management of ARIA involves monitoring and temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment 4.
- Lecanemab can be administered without titration with a modest incidence of ARIA, and its use requires clinician and institutional preparedness, as well as protocols for management of serious events 3, 5.
- The prognosis of patients with ARIA is generally good, with most cases being transient and asymptomatic, but some cases can be serious or fatal 3, 4.
Risk Factors for ARIA
- APOE4 homozygous carriers are at higher risk for ARIA 3, 5.
- Anticoagulation increases the risk of hemorrhage, and patients requiring anticoagulants should not receive lecanemab until more data regarding this interaction are available 3.
- Maximum lecanemab serum concentration is correlated with ARIA-E incidence 5.
Monitoring and Management of ARIA
- Monitoring guidelines for ARIA are detailed in the Appropriate Use Recommendations (AURs) for lecanemab 3.
- Simple magnetic resonance imaging (MRI) sequences are likely sufficient for effective detection of ARIA cases 4.
- Increased awareness and education of ARIA among clinicians and radiologists is vital 4.
- Treatment should be continued with caution and regular monitoring in the event of ARIA 4.