Raising the Clinical Bar Beyond Current Biologics in Uncontrolled Persistent Asthma: Translating Emerging Data in Future Clinical Decisions

Abstract

Asthma is a heterogeneous disease with multiple phenotypes, caused by a complex interplay of inflammatory pathways. Up to 70% of patients with asthma have Type 2 inflammation, characterised by the presence of interleukin (IL)-4, IL-5, and IL-13. Uncontrolled persistent asthma represents a considerable disease burden associated with a higher rate of exacerbations, more frequent hospitalisations, greater oral corticosteroid (OCS) use, more impaired lung function, reduced health-related quality of life (QoL), and Type 2 inflammatory comorbidities versus controlled asthma. There remains an unmet need for new therapies for patients with uncontrolled persistent asthma. Several agents targeting mediators of Type 2 inflammation are in clinical development for severe asthma, including prostaglandin D2 receptor 2 (DP2)/chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) antagonists and monoclonal antibodies (mAb) that specifically bind IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and IL-4 receptor (IL-4Rα). Dupilumab blocks signalling of IL-4 and IL-13 and is under investigation in various diseases driven by Type 2 inflammation. In Phase III clinical trials in patients with uncontrolled, persistent asthma, dupilumab was well tolerated and demonstrated significant efficacy versus placebo in reducing the rate of asthma exacerbations, and improving lung function, asthma symptoms, and QoL. This article summarises the proceedings of a symposium held at the European Academy of Allergy and Clinical Immunology (EAACI) 2018 Congress, which brought together an international faculty of experts to explore current understandings of asthma pathophysiology, with particular focus on Type 2 inflammatory pathways, and to provide an overview of current therapies, unmet medical needs, and the potential role of emerging biologics in the treatment of uncontrolled persistent asthma.