Positioning of Tezepelumab in severe asthma

Abstract

Asthma is one of the most common chronic diseases, and the estimated prevalence of severe asthma is 3-10% of the total asthmatic population. There is a need for additional biologic treatments that have high efficacy across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit one or two specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 inflammation cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal antibody immunoglobulin G2λ (IgG2λ) directed against the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial-derivate cytokine, preventing the binding of TSLP to its receptor and reducing the immune stimuli that TSLP can perform in different endotypes of asthma. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5 and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualised asthma exacerbation rate in patients with either high or low levels of T2 inflammation biomarkers, although the effect was greater among those with high levels, and it has been shown to improve asthma control, quality of life and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used in the whole spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, members of the SEAIC Asthma Committee.