Pediatric Atopic Dermatitis: Unmet Needs and Real-World Outcomes of Dupilumab Treatment

Abstract

Atopic dermatitis (AD) imposes a substantial burden on pediatric patients and their families, which increases with disease severity. For decades, systemic treatment for moderate-to-severe pediatric AD relied on the off-label use of conventional immunosuppressants. The approval of dupilumab, a monoclonal antibody targeting IL-4 and IL-13 signaling, marked the introduction of the first targeted therapy for patients aged six months and older with (moderate-to) severe AD. This thesis aims to deepen understanding of the unmet needs and real-world outcomes of dupilumab treatment in pediatric AD. It explores the broad impact of AD on children and their families, including economic and humanistic burdens, and highlights the variability in treatment goals and preferences among young patients and their caregivers. It also examines the prevalence of physician-diagnosed atopic comorbidities, such as asthma, allergic rhinitis, and the often under-recognized ocular surface disease, in pediatric patients with (moderate-to) severe AD. Subsequently, this thesis investigates the real-world effectiveness and safety of dupilumab in comparison to conventional systemic therapies. It explores the incidence and risk factors of dupilumab-associated ocular side effects and assesses both local and systemic immune responses using serum and tape strip sampling. Finally, it examines the effects of dupilumab on type 2-mediated comorbidities, including changes in food- and aeroallergen-specific IgE levels and pulmonary outcomes. By addressing the multidimensional burden of pediatric AD and evaluating the clinical and immunological effects of dupilumab, this thesis contributes to optimizing treatment strategies and advancing a more personalized approach to managing pediatric AD and improving patient outcomes.