What is the typical time frame for imaging findings of Amyloid-Related Imaging Abnormalities (ARIA) to occur after initiation of aducanumab (aducanumab) therapy?

Timing of ARIA Imaging Findings After Aducanumab Initiation

Imaging findings of Amyloid-Related Imaging Abnormalities (ARIA) typically occur within the first 8 doses of aducanumab therapy, with approximately 73% of initial ARIA-E events occurring during this early treatment period. 1

Types and Detection of ARIA

ARIA consists of two main types:

1. ARIA-E (edema/effusion):

   • Presents as parenchymal edema and/or sulcal "effusions"
   • Characterized by increased parenchymal T2 signal with potential mass effect
   • Non-suppression of sulcal CSF signal on T2 FLAIR images
   • Occurs in up to 35-36% of patients receiving aducanumab 2

2. ARIA-H (hemorrhage):

   • Manifests as parenchymal microhemorrhages and/or superficial siderosis
   • Incidence ranging from 15-20% in clinical trials 2

Both forms of ARIA are only detectable on noncontrast brain MRI and cannot be reliably detected on CT. 2

Temporal Pattern of ARIA Development

The timing of ARIA development follows a specific pattern:

• Most ARIA-E events (72.7%) occur within the first 8 doses of aducanumab 1
• Symptomatic cases have generally occurred within 4 to 8 weeks after infusion 2
• ARIA tends to be transient and typically occurs early in treatment, with risk decreasing later in treatment 3
• ARIA-E typically resolves radiographically in most cases (98.2%), with 82.8% resolving within 16 weeks 1

Risk Factors for ARIA

Several factors increase the risk of developing ARIA:

• APOE ε4 carrier status: The strongest genetic risk factor 4

  • ε4/ε4 homozygotes: OR = 4.28 for ARIA-E
  • ε3/ε4 heterozygotes: OR = 1.74 for ARIA-E

• Dose of medication: Higher doses associated with increased risk 2

Monitoring Recommendations

Based on clinical guidelines, MRI monitoring should follow this schedule:

• Pretreatment MRI within 12 months of initiation of therapy
• Routine posttreatment MRIs during therapy before the:
  • 5th infusion
  • 7th infusion
  • 14th infusion 2

Additional MRIs should be performed if patients develop clinical signs and symptoms that may indicate ARIA development. 2

Clinical Presentation

ARIA can be symptomatic or asymptomatic:

• Approximately 26% of patients with ARIA-E experience symptoms 1
• Common symptoms include:
  • Headache (46.6%)
  • Confusion (14.6%)
  • Dizziness (10.7%)
  • Nausea (7.8%) 1

Management of ARIA

Management depends on clinical symptoms and MRI grading severity:

• Detection of ARIA may require modification of the antiamyloid MAB therapy:
  • Temporary cessation of treatment
  • Permanent discontinuation in severe cases
  • Possible use of corticosteroids or antiepileptic treatment 2

Important Considerations

• ARIA is primarily detected using specific MRI sequences: DWI, T2 FLAIR, and T2* GRE or SWI 2
• 3T MRI provides greater sensitivity for detection of abnormalities, particularly microhemorrhages 2
• ARIA cannot be reliably detected on CT scans 2
• The main differential diagnosis for ARIA is CAA-ri/ABRA, with the discriminating feature being the history of anti-amyloid MAB therapy 2

Pitfalls to Avoid

1. Relying on CT imaging: ARIA is only reliably detected on MRI
2. Missing the monitoring window: Most ARIA occurs during the titration period
3. Overlooking mild symptoms: Even subtle symptoms during the first 8 doses should prompt evaluation
4. Failing to identify high-risk patients: APOE ε4 carriers require particularly vigilant monitoring
5. Inadequate MRI sequences: Ensure DWI, T2 FLAIR, and T2* GRE or SWI sequences are included

Understanding the typical timeframe of ARIA development is crucial for implementing appropriate monitoring strategies and ensuring patient safety during aducanumab therapy.