Pragmatic Clinical Perspective on Biologics for Severe Refractory Type 2 Asthma

Abstract

Patients with severe refractory asthma present a challenging clinical conundrum for practicing clinicians. Biologics that target key mediators in the type 2 inflammation cascade, including IL-4, IL-5, IL-13, and IgE, can be effective strategies for these patients. However, with various biologics available, choosing the optimal one for a particular patient becomes a nuanced decision. We propose a pragmatic algorithm that identifies the optimal biologic class for patients who have specific type 2 disease endotypes. Patients with eosinophilic endotypes fare well with anti-IL-5(rα) medications, comprising mepolizumab, benralizumab, and reslizumab because they have been shown to reduce exacerbations in severe eosinophilic asthma by approximately 50%. In patients with fractional exhaled nitric oxide-high endotypes, anti-IL-4rα such as dupilumab is deemed to be most effective and has demonstrated a 47% reduction in asthma exacerbations. For patients with severe uncontrolled allergic asthma, anti-IgE (omalizumab) is effective and has been shown to confer a 25% reduction in asthma exacerbations. Type 2 comorbidities including chronic rhinosinusitis with nasal polyps, atopic dermatitis, chronic idiopathic urticaria, and eosinophilic esophagitis are important to bear in mind before the prescription of biologics. Further head-to-head studies are indicated to compare biologics in patients with mixed endotypes according to peripheral blood eosinophils, fractional exhaled nitric oxide, and allergic status. The evidence strongly supports endotype-driven prescribing of biologics to achieve clinically relevant outcomes in severe refractory asthma and related comorbidities.

Keywords: Allergy; Asthma; Benralizumab; Dupilumab; Eosinophils; Feno; Mepolizumab; Omalizumab; Type 2 inflammation.