Baseline Clinical, Hormonal and Molecular Markers Associated with Clinical Response to IL-23 Antagonism in Hidradenitis Suppurativa: A Prospective Cohort Study

Abstract

Background: Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. 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: 18 of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone, and decreased levels of FSH. Stratification by clinical responders/non responders identified differentially expressed 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. Conclusions: Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c+ cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.