Update on biologic and small molecules treatments in pediatric allergic diseases

Biologics have revolutionized the treatment of severe allergic diseases in children that cannot be controlled by conventional treatments. These diseases are commonly driven by dysregulation of immune response, often driven by Type 2 pathways. By targeting them, biologics have the potential for treating one or more allergic diseases. Thus, a "treat to target" strategy is now prioritized, allowing treatment of allergic diseases in a personalized approach. The pioneer anti-IgE monoclonal antibody, omalizumab, was initially indicated for the treatment of moderate to severe allergic asthma and is now indicated for chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), and food allergy (FA), highlighting the ability of biologics to target multiple allergic diseases. Other biologics have been developed in asthma and other allergic diseases, including mepolizumab (anti-IL5), benralizumab (anti-IL5 receptor), dupilumab (anti-IL-4 receptor α), and more recently tezepelumab (anti-TSLP). Clinical trials in children and/or teenagers have demonstrated their efficacy and safety, confirmed by real-life studies, in asthma, atopic dermatitis (AD), CSU, and more recently in eosinophilic esophagitis (EoE) and FA. Beyond biologics, small molecules such as Janus kinase inhibitors target other key pathways and have already been approved in AD, with ongoing clinical trials in other allergic diseases. In the pediatric specific context, these treatments raise questions, particularly regarding the choice of biologics and the goals. In the long term, the sustained efficacy, safety and impact on the natural history of allergic diseases need to be further studied. The aim of this review is to discuss the most recent data in the use of biologics and small molecules in pediatric allergic diseases and to highlight the remaining gaps in knowledge.