Determinants of systemic treatment response in atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczema. Its heterogeneous pathophysiology involves epidermal barrier dysfunction, immune dysregulation, and alterations of the skin microbiome. Despite major advances through targeted therapies, predictors of individual treatment response remain poorly defined. This thesis investigates systemic therapies for AD by integrating real-world registry data, clinical trials, and molecular skin analyses. First, data from the TREATgermany registry were used to compare long-term effectiveness, safety, and drug survival of dupilumab and ciclosporin. Dupilumab showed superior drug survival, a favorable safety profile, and sustained clinical effectiveness under real-life conditions. To extend these findings to pediatric patients, interim data from the TREATkids registry were analyzed. Dupilumab significantly reduced disease severity and improved quality of life in children and adolescents. Proteomic analysis of tape-stripped stratum corneum samples demonstrated reductions in inflammatory and barrier-related proteins, supporting molecular recovery and the feasibility of minimally invasive skin sampling. The third study assessed IL-13 blockade with tralokinumab in adults with moderate-to-severe AD. Treatment led to significant clinical improvement, enhanced barrier function, reduced epidermal spongiosis, and normalization of key structural proteins. Proteomic and microbiome analyses revealed reduced inflammatory signatures and shifts toward a healthier microbial composition. Finally, a Phase IV clinical and translational study examined selective JAK1 inhibition with abrocitinib. Rapid clinical improvement was accompanied by restoration of barrier integrity, downregulation of inflammatory proteins, and normalization of skin physiology and microbial diversity.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Christian-Albrechts-Universität zu Kiel

Year

2026

Author dc:creator

• Sander, Nicole

Contributors dc:contributor

• Weidinger, Stephan
• Holtgrewe Stukenbrock, Eva

• Atopic Dermatitis
• Systemic treatments
• Dupilumab
• Tralokinumab
• Abrocitinib
• Skin barrier

Repository record source_url

https://macau.uni-kiel.de/receive/macau_mods_00007892

OAI identifier oai:identifier

oai:macau.uni-kiel.de:macau_mods_00007892