Novel Biological Therapies in Severe Asthma: Targeting the Right Trait

Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments. Although in most patients the disease can be controlled by some combination of pharmacologic agents, in some 5-10% of patients the disease remains uncontrolled. Several monoclonal antibodies (mAbs) targeting pathogenetic molecules (e.g., IgE, IL-5, IL- 5Rα, IL-4, IL-13, TSLP) are currently available or under development for the treatment of different forms of severe type 2 asthma. The identification of diagnostic and predictive biomarkers (e.g., IgE, blood eosinophil count, FeNO, periostin, etc.) has revolutioned the field of targeted therapy in severe asthma. Monoclonal antibodies targeting Th2-driven inflammation are generally safe in adult patients with moderate-to-severe asthma. The long-term safety of these biologics is a relevant issue that should be addressed. Unfortunately, little is known about non-type 2 asthma. Further studies are needed to identify biomarkers to guide targeted therapies of different forms of non-type 2 asthma.