Anti-Amyloid Beta Plaque Monoclonal Antibody

Aka: Anti-Amyloid Beta Plaque Monoclonal Antibody, Anti-Aß mAb, Humanized Immunoglobulin Gamma 1 Monoclonal Antibody, Aducanumab, Aduhelm, Lecanemab, Leqembi, Donanemab, Kisunla

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II. Indications

  1. Alzheimer's Disease with Amyloid Beta Plaque
    1. Mild Cognitive Impairment or Dementia (MMSE 20-28) AND
    2. Confirmed amyloid beta related findings

III. Contraindications

  1. Bleeding risk
  2. Concurrent Anticoagulation or antiplatelet agents

IV. Mechanism

  1. Selectively bind amyloid beta Plaques in the CNS

V. Precautions

  1. Aducanumab, the prototype, was FDA approved in 2021 with much controversy
    1. FDA over-rode its own advisory committee's vote (10 against and 1 in favor) to not approve
  2. Lecanemab was FDA approved via the accelerated approval pathway in 2023, with little better evidence than Aducanumab
  3. Adverse effects may significantly impact emergency department care
    1. ARIA-E (cerebral edema and effusions)
    2. ARIA-H (cerebral Hemorrhages)
    3. May present as CVA mimic (Altered Mental Status, Dizziness, confusion, Ataxia)
    4. Anti-amyloid MAB agents are considered contraindications to CVA Thrombolysis
    5. Stop Anti-amyloid MAB agents if Anticoagulation (or antiplatelet agents) are needed (e.g. Venous Thromboembolism)

VI. Medications

  1. Aducanumab (Aduhelm)
    1. Monoclonal Antibody infused IV every 4 weeks at a cost of $28,200 to $56,000 per year
      1. May reduce amyloid beta Plaque, but does not appear to improve cognitive function
      2. Risk of CNS microhemorrhages and edema requiring 3 MRIs in first year of use
      3. FDA approved, over-riding its own advisory committee's vote (10 against and 1 in favor) to not approve
    2. Infused over 45 to 60 minutes
      1. Start: 1 mg/kg for first 2 infusions
      2. Next: 3 mg/kg for next 2 infusions
      3. Next: 6 mg/kg for next 2 infusions
      4. Then: 10 mg/kg for maintenance
    3. References
      1. (2021) Presc Lett 28(8): 43
      2. Walsh (2021) BMJ 374:n1682 [PubMed]
  2. Lecanemab (Leqembi)
    1. Infusion dose: 10 mg/kg over 60 minutes
    2. Monoclonal Antibody infused IV every 2 weeks at a cost of $26,500 per year
      1. Risk of CNS microhemorrhages (NNH 15) and edema requiring 3 MRIs in first 18 months of use
      2. May reduce amyloid beta Plaque, but does not appear to improve cognitive function
      3. As with Aducanumab, FDA approved via the accelerated approval pathway
    3. References
      1. (2023) Presc Lett 30(4): 24
  3. Donanemab (Kisunla)
    1. Infused IV weekly over 30 minutes starting at 700 mg for the first 3 weeks, then increase to 1400 mg

VII. Efficacy

  1. May reduce amyloid beta Plaque, but does not appear to improve cognitive function
  2. No significant clinically meaningful benefit, high risk of harm, and at cost >$20,000 per year
    1. Ebell (2024) Ann Fam Med 22(1): 50-62 [PubMed]

VIII. Adverse Effects

  1. Adverse effect frequency varies by agent
    1. This list represents a composite of similar mechanism agents
  2. Infusion Reaction (20% of patients)
    1. Fever
    2. Chills
    3. Headache
    4. Rash
  3. Amyloid-Related Imaging Abnormalities (ARIA)
    1. Risk of CNS microhemorrhages and edema (NNH 13)
    2. May present with Altered Mental Status, Dizziness, confusion, Ataxia (may mimic CVA)
    3. Requires 3 MRIs in first 12 to 18 months of use (including baseline)
      1. Microhemorrhages are not visible on CT, making these agents a contraindication to Thrombolytics
    4. ARIA-E (cerebral edema and effusions)
    5. ARIA-H (cerebral Hemorrhages)
  4. Neurologic symptoms associated with Amyloid-Related Changes on Imaging (3% of patients, NNH 36)
    1. Increased risk with APOE-4 Homozygotes
    2. Headache
    3. Mental Status Changes
    4. Confusion
    5. Tremor
    6. Gait Disturbance
  5. Seizures (0.7% of patients)

IX. Drug Interactions

  1. Anticoagulants or antiplatelet agents
    1. Stop Anti-amyloid MAB agents if Anticoagulation is initiated
  2. Thrombolytics
    1. Contraindicated in patients taking Anti-amyloid MAB agents

X. References

  1. (2023) Presc Lett 30(4): 24
  2. (2021) Presc Lett 28(8): 43
  3. Hull (2025) Am Fam Physician 111(6):549-50 [PubMed]
  4. Walsh (2021) BMJ 374:n1682 [PubMed]
  5. Rech (2025) Ann Emerg Med 85(6): 526-36 +PMID: 39818674 [PubMed]

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