Baseline Clinical, Hormonal and Molecular Markers Associated with Clinical Response to IL-23 Antagonism in Hidradenitis Suppurativa. Baseline Clinical, Hormonal and Molecular Markers Associated with Clinical Response to IL-23 Antagonism in Hidradenitis Suppurativa

Background: Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. Clinical trials of IL-23 antagonism have shown high variability leading to abandonment of various clinical trials. IL-23 is known to interact with sex hormones in. monocytes, dendritic cells, and T cells. Relationships of IL-23 clinical response in HS to hormonal and molecular markers of inflammation has not been previously assessed. Objectives: To assess whether baseline clinical, hormonal, or molecular markers are associated with clinical response to IL-23 antagonism with Risankizumab in Hidradenitis Suppurativa. Methods: 26 individuals with Hurley Stage 2/3 disease were administered Risankizumab 150mg Week 0,4,12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Results: Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone, and decreased levels of FSH. nCounter gene expression identified consistent differential expressed genes to previously published RNAseq datasets. Stratification by clinical responders/non responders identified differentially expressed genes included TRAT1, TPSAB1/2, LTA, IL17A, CXCR1 as well as hormonally responsive genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to non-responders. CD11c+ cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Overall design: Baseline Data, Nanostring nCounter Human Fibrosis V2.0 Panel