Biologic Therapies in Pediatric Asthma

Abstract

Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced and very promising treatment alternative, eventually directing toward a successful precision medicine approach. The application of currently approved add-on treatments for severe asthma in children, namely omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab have been shown to be effective in terms of asthma control and exacerbation rate. However, to date, information is still lacking regarding its long-term use. As a result, data are frequently extrapolated from adult studies. Thus, the selection of the appropriate biologic agent, the potential predictors of good asthma response, and the long-term outcome in the pediatric population are still to be further investigated. The aim of the present study was to provide an overview of the current status of the latest evidence about all licensed monoclonal antibodies (mAbs) that have emerged and been applied to the field of asthma management. The innovative future targets are also briefly discussed.

Biologics and severe asthma in children

“…In deciding between these two, consideration of comorbidities may influence the decision, as dupilumab can also be used in patients with allergic comorbidities of eosinophilic esophagitis, atopic dermatitis, and chronic rhinosinusitis with nasal polyposis [4]. Dupilumab should not be used in patients with eosinophils !1500 cells/ml [13], suggesting that mepolizumab be considered in patients with eosinophils !1500 cells/ml, following careful consideration of other disorders that lead to eosinophilia. Some children and their families may prefer the dosing schedule for mepolizumab compared to dupilumab (every 4 weeks for mepolizumab doses rather than every 2 weeks for most dupilumab doses).…”

“…Its suppression of FeNO, eosinophils, and IgE suggests an upstream interruption of multiple inflammatory cascades through the blockade of TSLP effects [16 ▪▪ ]. Tezepelumab was overall well tolerated, with the most frequent adverse effects noted to be pharyngitis, arthralgias, and back pain [3 ▪ ,13].…”

Comparison between clinical trials and real-world evidence studies on biologics for severe asthma

“…The most evident is that patients are selected according to restrictive inclusion and exclusion criteria, which leads to select groups that do not always reflect the patients who are indeed eligible for a biologic, with heterogeneous characteristics considered exclusion criteria for pivotal studies (e.g., smoking habit, advanced age, comorbidities, and previous treatments). The rigidity of clinical protocols increases adherence to therapies, 119 which does not occur at this level in real practice, leading to an impact on asthma control that must be considered regardless of the effectiveness of the investigated agent. 120 Another limitation of clinical studies is the duration, which generally does not exceed 52 weeks except in extension studies, in which the duration may even reach 96 weeks (as in the recent TRAVERSE study on dupilumab).…”

“…In general, there are fewer studies involving children, and the extrapolation of the data from adult studies does not assume that the data completely overlap. 119 For these reasons, RWE studies will also be able to support research in this area, with the added benefit of evaluating long-term effectiveness and safety.…”

“…The target trial approach can be especially advantageous for improving the quality of big data. 118 , 119 …”