Selection of biologic agents for treatment of severe asthma in adolescents and adults

IgE: immunoglobulin E; IL: interleukin; ICS: inhaled glucocorticoid (aka inhaled corticosteroid); LABA: long-acting beta-agonist; LAMA: long-acting muscarinic antagonist; FeNO: fraction of exhaled nitric oxide; EGPA: eosinophilic granulomatosis with polyangiitis; ABPA: allergic bronchopulmonary aspergillosis; BEC: blood eosinophil count; BMI: body mass index; IV: intravenous; GCs: glucocorticoids.

* Severe poorly controlled asthma includes both of the following: 1) Demonstrated variable airflow limitation based on historical or current spirometry or bronchoprovocation testing without an alternative explanation and 2) Frequent symptoms (eg, cough, wheezing, or dyspnea more than twice a week, activity limitation, night-time wakening) AND/OR frequent exacerbations (≥1 hospitalization or ≥2 exacerbations requiring systemic glucocorticoids per year) despite optimized inhaled therapies including high-dose ICS plus LABA. Appropriate use of an asthma action plan, avoidance of environmental and medication triggers, and assessment and mitigation of common comorbidities (including potential helminthic infection) should be performed prior to initiating biologic therapy. Please refer to UpToDate topics on the management of severe asthma for further details.

¶ Glucocorticoids can mask elevations in eosinophils, FeNO, and IgE, so data obtained during steroid tapers or on chronic oral GCs are not as reliable. For patients who currently use chronic oral GCs, please refer to alternative algorithm "Selection of biologic agents for treatment of oral glucocorticoid-dependent severe asthma in adolescents and adults."

Δ We define childhood-onset asthma as asthma occurring before the age of 12 years. Childhood-onset asthma correlates with poor performance of anti-IL5/5R therapies.

◊ BEC and FeNO thresholds are not absolute, but are used to indicate a predominant signal. They have not been fully established in the literature and should be used along with clinical judgment. Patient response to biologics should be considered along a similar continuum.

§ In the absence of nasal polyposis, benralizumab is often preferred by patients given its every 2-month dosing regimen. Mepolizumab appears to show greater efficacy in the treatment of nasal polyposis. Reslizumab is less often used due to its IV formulation.

¥ Please refer to UpToDate content on hypereosinophilic syndromes for further discussion of specific causes of hypereosinophilia and their treatment.