II. Indications

  1. Third-line agents for refractory, Type 2 Asthma (Allergic Asthma or Eosinophilic Asthma, represents 50% of Asthma)
    1. Despite long acting Bronchodilator and Inhaled Corticosteroids
  2. One of the following findings present
    1. Blood Eosinophils >150/uL
    2. Sputum Eosinophils >2%
    3. Ferrous Nitrous Oxide >20 parts per billion
    4. Maintenance oral Corticosteroids required

III. Adverse Effects

  1. Anaphylaxis risk with all agents (several of the agents have a reported 0.2% risk)
    1. Consider prescribing Epinephrine injector

IV. Disadvantages

  1. $2500 to $4500 per month

V. Preparations: Interleukin-5 Antagonist (alpha-directed cytolytic Monoclonal Antibody, IgG1 Kappa)

  1. General
    1. May be used in age >=12 years old U.S. (>=18 years old Canada)
  2. Benralizumab (Fasenra)
    1. Dose 30 mg SQ every 4 weeks for 3 doses, then every 8 weeks
    2. Uncommon Headache, Pharyngitis
  3. Mepolizumab (Nucala)
    1. Dose 100 mg SQ q 4 weeks
    2. Common Headache, uncommon injection site irritation, back pain ,Fatigue
  4. References
    1. Ortega (2014) N Engl J Med 371(13): 1198-207 [PubMed]

VI. Preparations: Interleukin-5 Antagonist (Monoclonal Antibody, IgG4 Kappa)

  1. General
    1. May be used in age >=18 years old
  2. Reslizumab (Cinqair)
    1. Dose 3 mg/kg IV infusion over 20-50 min every 4 weeks
    2. Uncommon Pharyngitis
  3. References
    1. Nair (2017) N Engl J Med 376(25): 2448-58 [PubMed]

VII. Preparations: Interleukin-4 Alpha Receptor Antagonist

  1. General
    1. Use previously limited to age >= 6 years old
    2. As of 2022, approved for use down to age 6 years for moderate to severe Eczema
    3. Costs $3400/month in 2022, U.S.
    4. Live Vaccines are best completed at least 4 weeks before starting agent
  2. Indications
    1. Moderate to severe refractory, persistent Asthma
      1. High Eosinophil Counts or on chronic Systemic Corticosteroids
    2. Other Indications
      1. Eosinophilic Esophagitis
      2. Severe Atopic Eczema
      3. Chronic Sinusitis with Nasal Polyps
  3. Adverse Effects
    1. Eye (Conjunctivitis, Dry Eyes)
    2. Alopecia
    3. Arthralgias
    4. Rash
  4. Dupilumab (Dupixent)
    1. Adult Dose: 600 mg SQ once, then 300 mg SQ every 2 weeks
  5. References
    1. Castro (2018) N Engl J Med 378(26):2486-96 [PubMed]
    2. Rabe (2018) N Engl J Med 378(26): 2475-85 [PubMed]
    3. (2022) Presc Lett 29(7): 40-1

VIII. Preparations: Anti-IgE Antibody

  1. General
    1. May be used in age >=6 years old (if positive skin test or RAST to perennial allergen)
  2. Omalizumab (Xolair)
    1. Dose 75 to 375 mg SQ every 2-4 weeks (variable dose based on age, weight, serum IgE)
    2. Uncommon Arthralgias

IX. Management: Monitoring

  1. Re-evaluate every 3-6 months
  2. Taper off oral Corticosteroids and other add-on management

XI. References

Images: Related links to external sites (from Bing)

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Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
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Ontology: reslizumab (C1869620)

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Ontology: benralizumab (C2982078)

Definition (NCI) An afucosylated, humanized monoclonal antibody against the alpha chain of the interleukin-5 receptor (IL-5Ra), with potential anti-asthmatic activity. Upon administration, benralizumab binds to IL-5Ra and elicits an antibody-directed cell cytotoxicity (ADCC) against IL-5Ra-expressing cells. This induces apoptosis in IL-5Ra-expressing cells and may reduce asthmatic episodes. IL-5Ra, expressed on both eosinophils and basophils, plays a key role in asthma.
Concepts Immunologic Factor (T129) , Pharmacologic Substance (T121)
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