What are the serious side effects of donanemab (anti-amyloid beta antibody) infusions?

Serious Side Effects of Donanemab Infusions

Amyloid-Related Imaging Abnormalities (ARIA) are the most common serious side effects of donanemab infusions, occurring in approximately 24% of patients, with symptomatic cases in about 6% of treated individuals. 1, 2

ARIA (Amyloid-Related Imaging Abnormalities)

ARIA consists of two main types:

• ARIA-E (edema/effusion): Occurs in 24.4% of donanemab-treated patients compared to 1.9% in placebo 2

  • Presents as temporary swelling in areas of the brain
  • Usually resolves over time with monitoring
  • Symptomatic in approximately 5.8% of patients 2

• ARIA-H (hemorrhage): Occurs in 31.3% of donanemab-treated patients compared to 13.0% in placebo 2

  • Presents as microhemorrhages (25%) and superficial siderosis (15%) 1
  • Can occasionally include larger areas of bleeding in the brain 1

ARIA Risk Factors

Several factors increase the risk of developing ARIA:

• APOE ε4 homozygote status (highest risk) 1, 2
• Higher baseline amyloid burden 3, 2
• Presence of microhemorrhages or superficial siderosis on baseline MRI 3, 2
• Elevated mean arterial pressure 2
• Cardiovascular risk factors 3
• Concomitant use of antithrombotic medications 1

ARIA Symptoms

While most ARIA cases are asymptomatic, symptoms may include:

• Headache (most common) 1, 2
• Confusion 1, 2
• Dizziness 1
• Vision changes 1
• Nausea 1
• Aphasia 1
• Weakness 1
• Seizures 1

ARIA Timing

• Most ARIA-E events occur early in treatment, with 58.3% of first events occurring by the third infusion (approximately month 3) 2
• Risk decreases later in the treatment course 4

Other Serious Side Effects

Hypersensitivity Reactions

• Hypersensitivity reactions, including anaphylaxis and angioedema, occurred in 3% of donanemab-treated patients versus 0.7% with placebo 1
• These reactions can be serious and potentially life-threatening 1

Infusion-Related Reactions

• Occur in 9% of donanemab-treated patients versus 0.5% with placebo 1
• Symptoms include chills, erythema, nausea, vomiting, difficulty breathing, sweating, headache, chest pain, and blood pressure changes 1
• More common in patients who develop anti-drug antibodies (10% versus 2% in those without antibodies) 1

Gastrointestinal Complications

• Intestinal obstruction occurred in 0.4% of donanemab-treated patients versus none with placebo 1
• Intestinal perforation occurred in 0.2% of donanemab-treated patients versus 0.1% with placebo 1

Monitoring and Management

• MRI monitoring is required before treatment initiation and periodically during treatment to detect ARIA 1, 4
• Treatment may need to be temporarily or permanently discontinued based on ARIA severity 4
• Patients should be informed about potential symptoms and instructed to report them promptly 1
• APOE ε4 testing is recommended before treatment to assess ARIA risk 1
• Patients should carry information that they are receiving donanemab 1

Clinical Implications

• Benefit-risk assessment should consider that clinical benefit may be reduced in patients with high tau burden 3
• Careful patient selection and monitoring are essential, particularly for those with risk factors 3, 2
• Despite these serious side effects, donanemab has shown significant efficacy in reducing amyloid plaques and potentially slowing disease progression 5, 6

In conclusion, while donanemab offers promising benefits for Alzheimer's disease treatment, clinicians must be vigilant about monitoring for and managing ARIA and other serious side effects to ensure patient safety. 1, 2, 6