New biologics in severe asthma

15 Oct 2022 10:40 11:10
Azza Omar Speaker

The Global Initiative for Asthma (GINA) defines severe asthma as asthma that is not controlled by proper use of high-dose inhaled corticosteroids and long-acting beta-agonists or that worsens when high doses of these drugs are lowered. Severe asthma is a heterogenous disease characterized by multiple phenotypes. The complex and heterogeneous nature of severe asthma and despite recent advances, many patients continue to experience frequent exacerbations, an increased risk of hospitalization and a significantly reduced quality of life.

Research into the pathogenesis of asthma has led to the development of biologics that target cytokines directly involved in causing severe asthma symptoms. These cytokines include interleukin (IL)-4, IL-5 and IL-13, which are responsible for the high levels of eosinophils and immunoglobulin E (IgE) seen in some types of severe asthma.

Severe asthma is classified into three types based on patients’ response to treatment and the presence of certain biomarkers: allergic asthma, eosinophilic asthma, and noneosinophilic asthma.

As of 2021, GINA guidelines for the management of severe asthma include biologics as add-on therapy for severe allergic and eosinophilic asthma. Targeted biologic therapies have revolutionarily changed the management of severe asthma by affecting various clinical outcomes, mainly by reducing exacerbations and the use of maintenance corticosteroids, but also by improving lung function and patient quality of life.

Inhaled corticosteroids are not effective for those with noneosinophilic asthma, and only one of the currently available biologics targets a cytokine active in this type of asthma. That is hymic stromal lymphopoietin (TSLP) blocker is an epithelial cytokine responsible for starting a cascade of inflammation in asthma. Tezepelumab is the first agent with FDA-approved indications for all types of severe asthma, including noneosinophilic asthma, regardless of the presence of biomarkers.

The evolution persists as novel biologics targeting noneosinophilic asthma who do not respond to corticosteroids. Additionally, current biologics consist of injectable agents, many of which must be administered by a healthcare professional. A few companies are investigating new oral drugs and inhalers for use in patients with severe asthma.