The monoclonal antibody dupilumab (Dupixent) is used for treating multiple diseases, including moderate to severe atopic dermatitis (AD) - a dysregulation of several immunological pathways characterized by itchy skin lesions. Our study aimed to elucidate downstream effects of dupilumab in AD as well as to describe potential differences in systemic versus local effects. We enrolled 8 subjects with moderate to severe AD and collected blood, lesional skin biopsies, as well as interstitial fluid via dermal open flow microperfusion (dOFM) from lesional as well as non-lesional sites before and after treatment with dupilumab. We analyzed immune cell populations in blood and interstitial fluid using flow cytometry. Cytokines were investigated with targeted MSD assays as well as analysis by OLINK. We found that after treatment and amelioration of lesions several cytokines (ie. IL6, CXCL8, CCL7, IL1B, IL33, OLR1, OSM) trend upwards in interstitial fluid collected from lesional as well as non-lesional skin in contrast to a downwards trend in plasma. Additionally, in diluted interstitial fluid concentrations of some of the mentioned cytokines exceed those found in plasma, again indicating upregulation in skin, but not systemically.
We were able to integrate several new pathways to the currently accepted model of AD pathogenesis and to further deepen our understanding of the complex local and systemic interactions modulated by dupilumab by using a broad analytical approach. By understanding these local mechanisms and treatment effects, it will be possible to identify new topical drugs targeting these pathways and therefore improving ease of treatment.

The monoclonal antibody dupilumab (Dupixent) is used for treating multiple diseases, including moderate to severe atopic dermatitis (AD) - a dysregulation of several immunological pathways characterized by itchy skin lesions. Our study aimed to elucidate downstream effects of dupilumab in AD as well as to describe potential differences in systemic versus local effects. We enrolled 8 subjects with moderate to severe AD and collected blood, lesional skin biopsies, as well as interstitial fluid via dermal open flow microperfusion (dOFM) from lesional as well as non-lesional sites before and after treatment with dupilumab. We analyzed immune cell populations in blood and interstitial fluid using flow cytometry. Cytokines were investigated with targeted MSD assays as well as analysis by OLINK. We found that after treatment and amelioration of lesions several cytokines trend upwards in interstitial fluid collected from lesional as well as non-lesional skin in contrast to a downwards trend in plasma. Additionally, in diluted interstitial fluid concentrations of some of the mentioned cytokines exceed those found in plasma, again indicating upregulation in skin, but not systemically.
We were able to integrate several new pathways to the currently accepted model of AD pathogenesis and to further deepen our understanding of the complex local and systemic interactions modulated by dupilumab by using a broad analytical approach. By understanding these local mechanisms and treatment effects, it will be possible to identify new topical drugs targeting these pathways and therefore improving ease of treatment.

LB033 - Clinical trial using dermal open flow microperfusion (dOFM) elucidates mechanisms of dupilumab (Dupixent) on downstream signal pathways and indicates differences in local and systemic effects

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.