Thesis defense Celeste Boesjes

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Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. Until recently, adequate systemic treatment options for patients with moderate-to-severe AD were limited. Due to the increased understanding of the underlying pathophysiology of AD in the past decade, more targeted therapies for moderate-to-severe AD have been developed that address this unmet need. The advent of these new advanced systemic drugs since 2017, including biologics (i.e. dupilumab and tralokinumab) and Janus kinase (JAK)-inhibitors (i.e. baricitinib, upadacitinib and abrocitinib), therefore represents an important advancement in the therapeutic landscape for AD. In this thesis, including data from the real-life Dutch BioDay registry, we demonstrate that dupilumab treatment resulted in a significant improvement of clinical and patient-reported outcomes together with a significant decrease in severity-associated serum biomarkers and alterations in the skin microbiome moving it towards healthy skin. Effectiveness of dupilumab sustained even in the long-term use in both pediatric, adult and elderly patients as well as patients with or without pathogenic filaggrin variants, while the majority of patients was able to prolong their dosing interval. The JAK-inhibitors also showed to be effective treatment options for adult patients with moderate-to-severe AD, with upadacitinib and abrocitinib providing the highest effectiveness rates based on both physician and patients’ perspectives. Safety assessments showed that dupilumab has a favorable long-term safety profile, while the JAK-inhibitors still need to prove their safety in the long-term use.