From the Guidelines
Leqembi (lecanemab) can cause severe ARIA-E (amyloid-related imaging abnormalities with edema), which requires prompt management, and the prognosis is generally favorable with proper treatment, including immediate discontinuation of Leqembi and close monitoring with MRI, as supported by the Alzheimer's Association research roundtable workgroup 1.
Treatment and Management
For severe ARIA-E, the following steps are crucial:
- Immediate discontinuation of Leqembi
- Close monitoring with MRI to assess the resolution of edema
- Corticosteroids, such as dexamethasone or methylprednisolone, may be prescribed in symptomatic cases to reduce inflammation and edema
- Supportive care for symptoms like headache, confusion, or dizziness is essential to improve the patient's quality of life
Prognosis
The prognosis for severe ARIA-E is generally favorable with proper management, with most cases resolving within 4-16 weeks after treatment discontinuation, as observed in studies related to amyloid-modifying therapeutic trials 1. However, Leqembi should not be restarted until complete resolution of ARIA-E is confirmed by MRI. When restarting, physicians may consider a lower dose with gradual titration while monitoring closely for recurrence.
Risk Factors and Monitoring
The risk of ARIA-E is highest in APOE ε4 carriers and during the first few months of treatment, so more frequent MRI monitoring is recommended during this period, as suggested by the characteristics of ARIA-E observed in amyloid-modifying therapeutic trials 1. Patients and caregivers should be educated about symptoms requiring immediate medical attention, including headache, confusion, visual disturbances, and neurological changes.
From the Research
Leqembi Associated Severe ARIA-E Treatment and Prognosis
- Leqembi (Lecanemab) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets soluble aggregated Aβ species, and its use has been associated with amyloid-related imaging abnormalities (ARIA) 2, 3, 4.
- ARIA can cause brain edema (ARIA-E) and hemorrhage (ARIA-H), with ARIA-E being more common and associated with excessive neuroinflammation and saturation of perivascular clearance pathways 2.
- The risk of ARIA-E is higher at treatment initiation, in ApoE4 carriers, with higher dosage, and with >4 microhemorrhages on a baseline MRI 2, 3, 5.
- ARIA-E is generally asymptomatic, mild-to-moderate in severity, and occurs early (<3 months) in patients treated with lecanemab, with a low incidence of <10% and <3% symptomatic cases 4.
- Management of ARIA ranges from continued antibody treatment with monthly MRI monitoring for asymptomatic individuals to temporary or permanent suspension for symptomatic individuals or those with moderate to severe ARIA on MRI 2.
- An exposure-response model developed for lecanemab showed that the probability of ARIA-E was significantly correlated with model-predicted Cmax and predicted to be higher in subjects homozygous for APOE4 5.
- The incidence of isolated ARIA-H was not associated with lecanemab exposure and was similar between placebo and lecanemab-treated subjects 5.
- A brain MRI is required before lecanemab is initiated, before each scheduled dose escalation, and with any new neurologic sign or symptom to monitor for ARIA 2.
- Controlled studies regarding prevention and treatment of ARIA are lacking, but anecdotal evidence suggests that a pulse of intravenous corticosteroids may be of benefit, as well as a course of anticonvulsant for seizures 2.