Severe Asthma and Biological Therapies: Now and the Future

Abstract

Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.

The Evolution of Scientific Knowledge in Childhood Asthma over Time: A Surprising History

“…In addition, the use of omalizumab in pediatric patients is associated with a decrease in seasonal exacerbations induced by respiratory viruses [20,[22][23][24]. This finding could be explained by the ability of omalizumab to restore the IFN response against viral infections (rhinovirus and influenza), preventing exacerbations [17].…”

“…Plasma half-life time is about 26 days. Moreover, 75 mg and 150 mg prefilled syringes and 150 mg ampoules are currently available, with the possibility of being administered at home [17]. The omalizumab's target is the Fc region of free serum IgE, preventing its binding to FcεR1 receptors on mast cells and basophils, reducing free IgE and inducing the down-regulation of their receptors.…”

“…Indeed, potential predictors of good asthma response to omalizumab treatment are represented by biomarkers such as peripheral eosinophil counts (>260/µL), fractional exhaled nitric oxide (FeNO) (>20 ppb), the presence of allergen-driven symptoms and childhood-onset asthma [14]. On the contrary, children older than 12 years with exacerbations within the last 6 months, a forced expiratory volume in 1 s (FEV 1 ) < 90% of the predicted value, or comorbidities (obesity, gastroesophageal reflux, chronic rhinosinusitis, nasal polyps, and psychological disorders) have a greater risk of poor response to treatment [17]. Boek et al conducted a multicenter, placebocontrolled, three-arm, randomized, parallel-group study on 52 patients aged >18 years, with house dust mite (HDM)-driven asthma.…”

Identification of biomarkers associated with pediatric asthma using machine learning algorithms: A review

“…[6] Although there are some differences in the prescribing criteria for administrative approval between the US Food and Drug Administration and the European Medicines Agency, currently available biologic therapies, such as omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, are widely recognized for the treatment of variant asthma in children. [7] The aim of this study was to find key genes associated with childhood asthma, screen diagnostic biomarkers more comprehensively, efficiently, and accurately, and provide a basis for understanding the mechanism of asthma. This may have significant implications for the diagnosis and treatment of asthma in children.…”

“…[6] Although there are some differences in the prescribing criteria for administrative approval between the US Food and Drug Administration and the European Medicines Agency, currently available biologic therapies, such as omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, are widely recognized for the treatment of variant asthma in children. [7]…”