pulmonary disorders
Drug Treatment of Asthma
Immunomodulators
Immunomodulators includeomalizumab, an anti-IgE antibody, 3 antibodies to IL-5 (benralizumab,mepolizumab,reslizumab), and a monoclonal antibody that blocks IL-4 receptor-alpha to inhibit IL-4 and IL-13 signaling (dupilumab). Immunomodulators are used for the management of severe asthma refractory to a combination of step-up asthma therapies, usually high-dose inhaled corticosteroids with a long-acting beta2-adrenergic receptor agonist, and primarily characterized by elevated allergic inflammation biomarkers (serum IgE, blood eosinophil count). Drug selection should be individualized for each patient's clinical scenario based on route, frequency, cost, and collateral atopic disease. For example, a patient with atopic dermatitis and asthma could considerdupilumabbecause it is also used in patients with atopic dermatitis. Omalizumabis indicated for patients with severe, allergic asthma who have elevated IgE levels.Omalizumabmay decrease asthma exacerbations, corticosteroid requirements, and symptoms. Dosing is determined by a dosing chart based on the patient’s weight and IgE levels. The drug is administered subcutaneously every 2 to 4 weeks. Mepolizumab,reslizumab, andbenralizumabwere developed for use in patients with eosinophilic asthma and are monoclonal antibodies that block IL-5 or its receptor, IL-5R. IL-5 is a cytokine that promotes eosinophilic inflammation in the airways. Mepolizumabreduces exacerbation frequency, decreases asthma symptoms, and reduces the need for systemic corticosteroid therapy in patients with asthma who depend on chronic systemic corticosteroid therapy. Based on data from clinical trials, efficacy occurs with blood absolute eosinophil counts > 150/microL (0.15 × 109/L). In patients requiring chronic systemic corticosteroid therapy, the threshold for efficacy is unclear due to the suppressive effects of corticosteroids on blood eosinphil counts , yetmepolizumabhas been shown to reduce or eliminate the need for systemic corticosteroid therapy.Mepolizumabis administered subcutaneously 100 mg every 4 weeks. Reslizumabalso appears to reduce frequency of exacerbations and decrease asthma symptoms. In clinical trials, patients had blood absolute eosinophil counts of about 400/microL (0.4 × 109/L). In patients treated with chronic systemic corticosteroids, the eosinophil count threshold for efficacy is unclear.Reslizumabis administered 3 mg/kg IV over 20 to 50 minutes every 4 weeks. Benralizumabis a monoclonal antibody that binds to IL-5 receptors. It is indicated for the add-on maintenance treatment of severe asthma in patients aged 12 years or older with an eosinophilic phenotype. It has been shown to decrease exacerbation frequency and reduce and/or eliminate oral corticosteroid use. The recommended dose is 30 mg subcutaneously once every 4 weeks for 3 doses, followed by 30 mg once every 8 weeks. Dupilumabis a monoclonal antibody that blocks the IL-4R-alpha subunit, thereby simultaneously inhibiting IL-4 and IL-13 signaling. It is indicated for add-on maintenance treatment of patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma. The recommended dose is an initial dose of 400 mg subcutaneously followed by 200 mg every other week, or an initial dose of 600 mg subcutaneously followed by 300 mg every other week. The higher dosage is recommended for patients requiring concomitant oral corticosteroids for whom dose reductions and cessation of systemic corticosteroids is a goal. Clinicians who give any of these immunomodulators should be prepared to identify and treat Anaphylaxis or Prepare for possible anaphylactic or hypersensitivity reactions in patients being treated withomalizumab,mepolizumab,reslizumab,benralizumab, ordupilumabregardless of how such treatments have been tolerated previously. 