Pragmatic clinical perspective on biologics for severe refractory type 2 asthma

Patients with severe refractory asthma present a challenging clinical conundrum for practising clinicians. Biologics that target key mediators in the type 2 (T2) 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 which identifies the optimal biologic class for patients who have specific T2 disease endotypes. Patients with eosinophilic endotypes fare well with anti-IL5(rα) medications, comprising mepolizumab, benralizumab and reslizumab as they have been shown to reduce exacerbations in severe eosinophilic asthma by approximately 50%. In patients with FeNO-high endotypes, anti-IL4rα such as dupilumab is deemed to be most effective and has demonstrated a 47% reduction in asthma exacerbations although a recent indirect treatment comparison suggests further promising results. For patients with severe uncontrolled allergic asthma, anti-IgE (omalizumab) is effective and has been shown to confer a 25% reduction in asthma exacerbations. T2 comorbidities including chronic rhinosinusitis with nasal polyps, atopic dermatitis, chronic idiopathic urticaria and eosinophilic esophagitis are important to bear in mind prior to the prescription of biologics. Further head-to-head studies are indicated to compare biologics in patients with mixed endotypes according to peripheral blood eosinophils, FeNO and allergic status. The evidence strongly supports endotype-driven prescribing of biologics in order to achieve clinically relevant outcomes in severe refractory asthma and related comorbidities.