<scp>Interleukin‐17RA</scp> blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum

Background: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the IL-17 axis. Recently we reported clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS.

Objectives: To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response.

Methods: Ten participants that received 210 mg/1.5mL brodalumab subcutaneously at week 0, 1, 2, 4 and every 2 weeks after were included in this molecular profiling study (NCT03960268). RNA-sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high throughput proteomics of serum at baseline, week 4 and week 12 were assessed.

Results: At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin having no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated Lipocalin-2 (LCN2) in the skin and IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12.

Conclusions: IL-17RA inhibition by brodalumab impacts several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin and IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab