Hidradenitis suppurativa (HS) was an inflammatory skin disease caused by IL-17 axis dysfunction. Brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, was shown to be effective in patients with moderate-to-severe HS. For a study, the researchers sought to find indicators of treatment response and characterize the molecular response to brodalumab in HS skin and serum. The molecular profiling outline included 10 subjects who received 210 mg/1.5mL brodalumab subcutaneously at weeks 0, 1, 2, 4, and every 2 weeks after that (NCT03960268). At baseline, week 4, and week 12, RNA-sequencing and immunohistochemistry of nonlesional, perilesional, and lesional HS skin biopsies, as well as Olink high throughput proteomics of serum, were evaluated. Brodalumab decreased overall inflammation and improved psoriasis, keratinocyte, and neutrophil-related pathways by week 12. Despite the fact that there were no differences in gene expression between perilesional and lesional skin at the start, treatment response was best assessed in perilesional skin. Brodalumab therapy reduced the pathways implicated in neutrophil inflammation in serum. As evaluated in skin biopsies at week 12, patients with higher baseline expression of neutrophil-associated Lipocalin-2 (LCN2) in the skin and IL-17A in the blood had more significant declines in HS-related inflammatory cytokines. Brodalumab inhibited IL-17RA, which affected multiple pathogenic inflammatory axes in HS. Perilesional skin allowed for a reliable and valid evaluation of treatment response. LCN2 expression in the skin and IL-17A in the blood could have been employed as biomarkers to identify patients with a better molecular response to brodalumab.