Role of biologics targeting type 2 airway inflammation in asthma: what have we learned so far?

Abstract

Severe asthma is a heterogeneous syndrome that can be classified into distinct phenotypes and endotypes. In the type 2 (T2)-high endotype, multiple cytokines are produced that lead to eosinophilic inflammation. These cytokines and their receptors are targets for biologic therapies in patients with severe asthma who do not respond well to standard therapy with inhaled corticosteroids. In the last decade, an increasing number of biologic therapies have been developed targeting T2 inflammation. Clinical trials of therapies targeting immunoglobulin E as well as the T2 cytokines interleukin (IL)-4, IL-5, and IL-13 have demonstrated that these treatments improve asthma-related clinical outcomes and/or have steroid-sparing properties. The use of biomarkers of T2 inflammation can help to identify the subset of patients in whom these therapies may be most efficacious. Multiple biologic agents that are directed at other targets are currently in development, including thymic stromal lymphopoietin (TSLP), prostaglandin (PG)D2 receptor, IL-25, and IL-33. Biologics are emerging as a key component of severe asthma management. In patients with T2-high severe asthma, the addition of treatments targeting immunoglobulin E and IL-5 to standard therapy may lead to improvement in clinical outcomes. Other biologic therapies have shown promising preliminary results and need to be studied in further clinical trials. These biologic therapies in conjunction with biomarkers will lead to tailored therapy for asthma.