Genomic and phenotypic characterization of Investigator Global Assessment (IGA) scale based endotypes in atopic dermatitis

ABTRACT Background Atopic dermatitis (AD) is a heritable and heterogeneous inflammatory chronic skin disorder. Utilizing decision tree/supervised learning of extensive clinical, molecular and genetic data, we aimed to define distinct AD endotypes. Methods Deep phenotyping and whole-genome sequencing was performed on samples obtained from participants of EPIONE, a randomized-controlled phase III study in AD patients with severe pruritus comprising mild (23%), moderate (64%) and severe (13%) AD as determined by AD Investigator Global Assessment scale. Three categories of analysis were performed: clinical associations, lab value associations (EOS, IgE, cytokines) and genetic analysis of whole-genome sequencing data Results Based on a decision tree, we found that five clinical features from the SCORing Atopic Dermatitis (SCORAD) Index can accurately differentiate between IGA severities. We observe a significant difference between severity and eosinophil counts (p Conclusion Our results suggest significant differences between severity groups across a number of features appear to constitute distinct endotypes with likely distinct causative factors. Differing underlying pathophysiology’s indicate endotype knowledge is critical to help guide therapeutic approaches to AD. Capsule summary AD is a heritable and heterogeneous skin disorder that makes the ‘one size fits all’ therapeutic approach suboptimal for patients with AD. We attempted to define AD endotypes based on clinical, molecular, and genetic characteristics. Clinical, CBC, and genetic associations all tend to suggest existence of separate endotypes.