How to manage symptomatic Amyloid-Related Imaging Abnormalities with Edema (ARIA-E) in patients undergoing Lecanemab (aducanumab) infusion therapy?

Management of Symptomatic ARIA-E in Lecanemab Infusion Therapy

Symptomatic ARIA-E in patients receiving lecanemab requires temporary suspension of treatment and may necessitate corticosteroid therapy, with treatment decisions based on symptom severity and MRI grading.

Understanding ARIA-E

• ARIA-E (Amyloid-Related Imaging Abnormalities with Edema) presents as parenchymal edema and/or sulcal "effusions" characterized by increased parenchymal T2 signal with potential mass effect and non-suppression of sulcal CSF signal on T2 FLAIR images 1
• ARIA-E occurs in approximately 12.6% of patients undergoing lecanemab therapy in clinical trials 1
• ARIA-E typically occurs early in treatment course, with risk decreasing later in treatment 2

Clinical Presentation of Symptomatic ARIA-E

• Common symptoms include headache, confusion, visual disturbances, dizziness, and gait difficulties 1, 3
• More severe presentations may include seizures (including electrographic seizures without overt clinical manifestations) 3, 4
• In rare cases, ischemic strokes have been reported as a potential feature of ARIA 4

Risk Factors for ARIA-E

• APOE ε4 carrier status, particularly homozygotes (33% of ε4/4 homozygotes vs. 4.3% of non-carriers developed ARIA-E in clinical trials) 1, 5
• Higher doses of anti-amyloid antibody therapy 1
• Pre-existing cerebrovascular pathology 6
• Presence of multiple microhemorrhages (≥4) 7, 5

Diagnostic Approach

• MRI is mandatory for detection of ARIA-E, as it cannot be reliably detected on CT 1
• Required MRI sequences include:
  • T2 FLAIR (for edema detection) 1
  • DWI (to assess for acute ischemia) 1
  • T2* GRE or SWI (for detection of microhemorrhages) 1
• 3T MRI provides greater sensitivity for detection compared to 1.5T 7, 6

Management Algorithm for Symptomatic ARIA-E

Step 1: Immediate Actions

• Temporarily suspend lecanemab infusions 1, 2
• Perform urgent brain MRI if not already done 1
• Grade ARIA-E severity based on MRI findings 1

Step 2: Symptomatic Management

• For mild symptoms (e.g., mild headache):

  • Symptomatic treatment with analgesics 2, 3
  • Monitor closely with repeat MRI in 2-4 weeks 1

• For moderate to severe symptoms (confusion, visual disturbances, gait difficulties):

  • Consider intravenous corticosteroid treatment (methylprednisolone) 1, 3, 8
  • Monitor for potential seizure activity, including subclinical seizures 4, 8
  • Consider anticonvulsant therapy (e.g., levetiracetam) if seizures are present or suspected 3, 8

Step 3: Blood Pressure Management

• Control hypertension if present, as malignant hypertension has been reported with ARIA 8
• Consider nicardipine or other antihypertensive agents if needed 8

Step 4: Follow-up Monitoring

• Perform regular follow-up MRIs until resolution of ARIA-E 1
• Most cases resolve within 4-16 weeks 2, 3

Step 5: Decision on Treatment Continuation

• For resolved asymptomatic ARIA-E: consider resuming treatment at the same or lower dose with careful monitoring 2
• For resolved symptomatic ARIA-E: consider permanent discontinuation of treatment, especially if symptoms were severe 1, 3
• For persistent ARIA-E or recurrent symptomatic episodes: permanently discontinue treatment 1

Important Caveats and Pitfalls

• ARIA-E may be accompanied by ARIA-H (hemorrhage), which requires separate management considerations 1
• Symptoms may not correlate with radiographic severity; asymptomatic patients may have extensive ARIA-E while symptomatic patients may have minimal findings 1, 2
• Differential diagnosis for ARIA-E includes posterior reversible encephalopathy syndrome, posterior multifocal leukoencephalopathy, subacute infarcts, meningitis, and vasculitis 1
• Limited data exist on the long-term clinical outcomes of patients with symptomatic ARIA-E, but preliminary analyses suggest that asymptomatic cases may not have significant impact on cognitive function 1
• Regular MRI monitoring is essential even after resolution to detect potential recurrence 1

Prevention Strategies

• Consider APOE ε4 testing before treatment to identify high-risk patients 1, 5
• Implement regular MRI monitoring as recommended (before the fifth, seventh, and fourteenth infusions) 1
• Perform immediate MRI for any new neurological symptoms during treatment 1