Many patients with asthma have type 2 inflammation. Type 2 inflammation, also known as T2-high asthma, is driven by presence of interleukin (IL)-4, IL-5, IL-13, eosinophils, and allergic inflammation.
Severe, persistent asthma is classified as having symptoms most days, waking with asthma once per week or more, and having low lung function despite use of medium- to high-dose inhaled corticosteroid treatment. Type 2 inflammation should be considered if a patient has evidence of elevated blood or sputum eosinophils, elevated fractional exhaled nitric oxide test, or asthma that seems to be allergen-driven. If these patients have evidence of T2 inflammation and continue to have uncontrolled symptoms, phenotypic assessment and perhaps starting targeted treatment with a biologic should be considered.
Omalizumab is an anti-immunoglobulin (Ig) E monoclonal antibody indicated in moderate to severe allergic asthma in patients aged 6 years or older. The indicated dose is dependent on patient’s IgE level and weight, and is given every 2 or 4 weeks via subcutaneous injection. Omalizumab is most effective in patients with a total IgE level ≥30 kU/L. Patients on omalizumab have been shown to have fewer exacerbations, require less steroids, and have a mild improvement in lung function.
Dupilumab is an anti–IL-4 and anti–IL-13 targeted monoclonal antibody. It is indicated in patients aged 12 years and older with moderate to severe eosinophilic or steroid-dependent asthma. Dupilumab is most effective in patients with eosinophil levels ≥150 cells/mcL. It is administered every 2 weeks via subcutaneous injection and can be given at home. Dupilumab has been shown to result in reduced exacerbations, less steroid use (by up to 75% or more), and moderate improvements in lung function.
Finally, there are three biologics that inhibit IL-5. Mepolizumab and reslizumab block the IL-5 pathway; benralizumab has a slightly different mechanism of action and blocks the IL-5 receptor on the surface of the eosinophil. Mepolizumab is approved for severe eosinophilic asthma in patients aged 6 years and older. Based on study data, it is most effective in patients with an eosinophil count of ≥150 cells/mcL. Mepolizumab is administered every 4 weeks via subcutaneous injection. Reslizumab is indicated for severe eosinophilic asthma in patients aged 18 years and older. It is most effective in patients with eosinophil count of ≥400 cells/mcL. The intravenous administration of reslizumab allows for weight-based dosing, and it can be considered in obese patients. Finally, benralizumab is indicated in severe eosinophilic asthma in patients aged 12 years and older. It is typically used in patients with eosinophil levels ≥300 cells/mcL. Benralizumab is given via subcutaneous injection every 4 weeks initially, then every 8 weeks for maintenance. Both benralizumab and mepolizumab can be administered at home. All of the anti–IL-5 therapies have been shown to reduce exacerbations and steroid use and improve lung function.
With further research, more targeted biologic therapies will become available for patients. It is important for providers to know that these medications are available and to appropriately refer patients with moderate to severe asthma to an allergist or pulmonologist.