Biologics and small molecules: the re-evolution in the treatment of atopic dermatitis in children and adolescents. Current state of the art and future perspectives

In recent years, the understanding of atopic dermatitis (AD) pathogenetic mechanisms has expanded and now it is recognized that Th2 immune axis dysregulation is pivotal to AD pathogenesis. The advent of biological drugs and small molecules have marked a revolution in the treatment of AD. Dupilumab, targeting IL-4 and IL-13, has been the first to demonstrate efficacy in treating moderate to severe AD by modulating type-2 inflammation pathways. Increasing knowledge of different immune axis and cytokines has fueled the development of new biologics and small molecules. JAK inhibitors which targets the JAK-STAT pathway, involved in cytokine signaling, represent a promising novel therapeutic strategy, enlarging the treatment options for moderate to severe atopic dermatitis. This comprehensive review aims to provide an updated and critical overview of the drugs currently in use and under investigation for the treatment of moderate to severe AD in children and adolescents, along with addressing the unmet needs and future research perspectives. Biologics and small molecules offer the promise to enlarge the arsenal options for the treatment of AD. As the patient's response to biologics depends on their pheno-endotype of AD, choosing the right is crucial for ensuring therapy success.