Alterations to the Hidradenitis Suppurativa Serum Proteome with Spleen Tyrosine Kinase Antagonism: Proteomic Results from a Phase 2 Clinical Trial

Hidradenitis Suppurativa (HS) is a disease in great need of novel therapies. Given the heterogeneous nature of the disease and the variable response to therapies, biomarkers are essential to predict response to therapies and increase our understanding of disease pathogenesis. Our recent Phase 2 clinical trial of Spleen Tyrosine Kinase antagonism using Fostamatinib in Hidradenitis Suppurativa demonstrated a 75% clinical response with the greatest benefit in individuals with elevated serum inflammation and Immunoglobulin G. We herein present results of an in-depth serum proteomic analysis in this patient cohort identifying downregulation of IL-12B, as well as B-cell associated proteins CCL19 and CCL20, and Interferon-gamma mediated proteins CXCL10 and CX3CL1. Clinical responders demonstrated greater reduction in serum IL-17A, IL-6, IL-8 and CX3CL1 compared to clinical non-responders. Baseline levels of CCL28 were associated with clinical response to fostamatinib therapy at week 12. Overall, this suggests that Fostamatinib, by targeting b cell receptor and Fc receptor activity in B cells, monocytes and macrophages has significant molecular impact on the inflammatory serum proteome of HS. Additional, potential therapeutic biomarkers may aid in patient selection for targeted therapy.