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 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
Unknown Impact on Immune Response to Helminth Infections: patients with preexisting helminth infections should complete treatment of the infection prior to initiation of mepolizumab