An Updated Reappraisal of Dupilumab in Children and Adolescents with Severe Asthma

Abstract

Severe asthma (SA) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common phenotype in children and adolescents with SA. As a result, anti-inflammatory drugs, mainly corticosteroids (CSs), represent the first choice to reduce type 2 inflammation. However, SA patients may require high inhaled and oral CS doses to achieve and maintain asthma control. Some SA patients, despite the highest CS dosages, can even display uncontrolled asthma. Therefore, the biological era constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing against both IL-4 and IL-13, and has been approved for pediatric severe type 2 asthma. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with SA. There is convincing evidence that dupilumab is a safe and effective option in managing SA as it can reduce asthma exacerbations, reduce CS use, and improve lung function, asthma control, and quality of life, also for caregivers. However, a thorough diagnostic pathway is mandatory, mainly concerning phenotyping. In fact, the ideal eligible candidate is a child or adolescent with a type 2 allergic phenotype.

Keywords: allergic asthma; dupilumab; phenotype; severe asthma; type 2 inflammation.

Figure 1

Pragmatic management of children and adolescents with severe asthma. ACT: asthma control test; ACQ: asthma control questionnaire; COSMA: core outcomes measures for asthma; QoL: quality of life; CRSwNP: chronic rhinosinusitis with nasal polyps; GERD: gastroesophageal reflux disease; OSAS: obstructive sleep apnea syndrome; FeNO: fractional exhaled nitric oxide: AD: atopic dermatitis.