Mepolizumab (Nucala)

Indications

Asthma (see Asthma, [[Asthma]])

  • DREAM Trial in Asthma with Eosinophilic Inflammation (Sputum Eosinophilia, Peripheral Eosinophilia, Increased Exhaled NO, or Decreased Control with Inhaled/Systemic Steroid Taper) (Severe Eosinophilic Asthma) (Lancet, 2012) [MEDLINE]
    • Mepolizumab Decreased Asthma Exacerbations in Severe Eosinophilic Asthma
  • MENSA Trial of Mepolizumab in Asthma with Eosinophilic Inflammation (Severe Eosinophilic Asthma) (Peripheral Eosinophilia) Without Control on High-Dose Inhaled Corticosteroids (NEJM, 2014) [MEDLINE]
    • Mepolizumab (IV, SQ) Decreased Asthma Exacerbations
    • Mepolizumab Improved FEV1
    • Mepolizumab Improved 5-Item Asthma Control Questionnaire Scores (ACQ-5): marker of asthma symptom control
    • Mepolizumab Improved St. George’s Respiratory Questionnaire (SGRQ) Scores
  • SIRIUS Trial in Asthma with Eosinophilic Inflammation (Peripheral Eosinophilia) Treated with Systemic Corticosteroids (NEJM, 2014) [MEDLINE]
    • Mepolizumab Decreased Asthma Exacerbations
    • Mepolizumab had a Significant Glucocorticoid-Sparing Effect
    • Mepolizumab Improved 5-Item Asthma Control Questionnaire Scores (ACQ-5): marker of asthma symptom control

Contraindications

  • Use in Children <12 y/o
  • Use in Acute Asthma Exacerbation/Status Asthmaticus (see Asthma, [[Asthma]])

Pharmacology

  • Humanized Monoclonal Antibody Against Interleukin-5 (IL-5)
    • IL-5 is the main cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils
    • Mepolizumab decreases the production and survival of eosinophils

Metabolism

  • Proteolytic Degradation via Enzymes that are Widely Distributed Throughout Body

Pharmacokinetics

  • Terminal Half-Life: 16-22 days

Administration

  • SQ (Upper Arm, Thigh, Abdomen): 100 mg

Prevaccination

  • Varicella-Zoster Vaccination (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]]): consider prior to mepolizumab

Dose Adjustment

  • Hepatic: no dose adjustment
  • Renal: no dose adjustment

Drug Interactions

  • Corticosteroids (see Corticosteroids, [[Corticosteroids]]): do not abruptly discontinue systemic/inhaled corticosteroids upon initiation of mepolizumab
    • Decrease in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroids

Adverse Effects

Cardiovascular Adverse Effects

  • Hypotension Associated with Hypersensitivity Reaction (see Hypotension, [[Hypotension]]): as below

Immunologic Adverse Effects

  • Hypersensitivity Reaction: typically occur within hours of administration

Infectious Adverse Effects

  • Unknown Impact on Immune Response to Helminth Infections: patients with preexisting helminth infections should complete treatment of the infection prior to initiation of mepolizumab
  • Herpes Zoster Infection (see Varicella-Zoster Virus, [[Varicella-Zoster Virus]])
    • Pre-Mepolizumab Varicella-Zoster Vaccination: should be considered

Neurologic Adverse Effects

  • Headache (see Headache, [[Headache]]): occurs in 19% of cases

Pulmonary Adverse Effects

  • Bronchospasm Associated with Hypersensitivity Reaction (see Obstructive Lung Disease, [[Obstructive Lung Disease): as above

References

  • Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-984 [MEDLINE]
  • Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-659 [MEDLINE]
  • MENSA Trial. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371:1198-1207 [MEDLINE]
  • SIRIUS Trial. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371:1189 [MEDLINE]