Table 1.

Immunomodulatory Biologic Agents Approved for Use in Asthma

Pathway	IgE	IL-4 and IL-13	IL-5
Mechanism	Blocks IgE-mediated immune stimulation	Binds to IL-4R alpha subunit and blocks IL-4 and IL-13 cytokine-induced inflammatory responses	Block IL-5 binding to the receptor and reduces survival of eosinophils
Medication	Omalizumab	Dupilumab	Mepolizumab	Benralizumab	Reslizumab
Target	Anti-IgE monoclonal antibody	Anti-IL-4R alpha monoclonal antibody	Anti-IL-5 monoclonal antibody	Anti-IL-5 alpha monoclonal antibody	Anti-IL-5 receptor monoclonal antibody
Considerations	Elevated IgE	Atopic dermatitis and/or eosinophilia	Eosinophilia	Eosinophilia	Eosinophilia
Indications	Add-on therapy for patients ≥ 6 y old with moderate-to-severe persistent asthma inadequately controlled on ICS and a total serum IgE level between 30 and 700 units/mL and a positive allergen test	Moderate to severe asthma in patients ≥ 12 y old; oral corticosteroid-dependent asthma or asthma with severe atopic dermatitis or chronic rhinosinusitis with nasal polyps	Severe asthma in patients ≥ 12 y old with eosinophilia	Severe asthma in patients ≥ 12 y old with eosinophilia	Severe asthma in patients ≥ 18 y old with eosinophilia
Dosing route	Subcutaneous	Subcutaneous	Subcutaneous	Subcutaneous	IV
Dosing interval	Every 2-4 wk depending on pretreatment serum IgE level	Every 2 wk	Every 4 wk	Every 4 wk for the first three doses, then once every 4 or 8 wk	Every 4 wk
Outcomes observed in clinical trials	Reduced exacerbations by approximately 25%-50% in subjects with an FEV1 between 40% and 80% predicted	Reduced exacerbations by approximately 50% in patients with severe asthma compared with placebo and improvement in FEV1 Among patients on oral glucocorticoids, 70% had a reduction in the dose, compared with 42% in placebo	Fewer exacerbations compared with placebo and reduced corticosteroid dose in patients requiring maintenance corticosteroids	Reduced exacerbation rate in moderate or severe asthma. In patients with eosinophil counts ≥ 300 cells/μL, rate ratio of < 0.55 for both dosing regimens and improved prebronchodilator FEV1. Reduced glucocorticoid use with an odds of reduction of 4.09 compared with placebo	Decreased asthma exacerbations by as much as 59%. Improvement in lung function. Improvement in asthma symptoms and asthma-related quality of life
Common (> 3%) or severe side effects	Headache (6%-12%) Arthralgias (3%-8%) Anaphylaxis (0.3%) – black box warning Serum sickness-like reaction Cardiovascular events, including transient ischemic attack and ischemic stroke Eosinophilic granulomatosis and polyangiitis	Injection site reaction (10%-18%) Oral herpes simplex infection (4%) Antibody response with neutralizing activity (2%-4%) Conjunctivitis (10%) Eosinophilic granulomatosis with polyangiitis and eosinophilic pneumonia Hypersensitivity reactions	Headache (19%) Injection site reaction (8%-15%)	Antibody response with neutralizing activity (12%) Headache (8%) Pharyngitis (5%)	Antibody to medication (5%) Transient increased creatine phosphokinase (20%) Oropharyngeal pain (3%) Increased malignancies observed at 6 mo (diverse types) Anaphylaxis (0.3%) – black box warning

Serious side effects are in bold font.