Pilot study of topical ruxolitinib demonstrates efficacy and blunting of heterogeneous inflammatory processes in mild hidradenitis suppurativa

Therapeutic options for mild hidradenitis suppurativa (HS) represent a significant gap in the current treatment landscape, with no FDA approved therapies for early stage HS. Topical JAnus Kinase inhibitors (JAKi) are a compelling option due to the known upregulation of inflammatory JAK signaling in HS lesions and the recent success of systemic JAKi for moderate to severe HS. This is a pilot, single-site, open-label, prospective 24-week clinical trial with topical ruxolitinib (NCT04414514). The goals of this study were to assess clinical efficacy in a pilot cohort and investigate the underlying biological mechanisms associated with clinical response. Male and female patients with mild HS (Hurley stage I or II), with active inflammatory nodules, were recruited. All subjects were observed for 8 weeks to monitor lesion counts (observational phase), then proceeded with active therapy (treatment phase) for 16 weeks. 1.5% topical ruxolitinib cream was applied twice daily, covering the entirety of each HS-affected body site. Clinician and patient reported outcome measures were recorded throughout the study. Lesional skin punch biopsies were obtained at the start and end of therapy for downstream mechanistic RNA-seq and histological analyses. Ten subjects enrolled in this study, four subjects dropped out of the study before the treatment phase of the trial. Six individuals with Hurley stage I (no tunnels) completed the entire study, with five of six successfully achieving HiSCR through 16 weeks of therapy. In this interim analysis, differential gene expression and gene set enrichment analyses revealed reduced activation of JAK-dependent IFN, IL-6, IL-2, and EGFR signaling, antimicrobial responses, and keratinocyte responses. In contrast, signatures of wound healing and lipid metabolism were increased following JAKi treatment, indicating a return toward homeostasis. Histological analyses revealed that clinically-responsive patients had significantly reduced epidermal and dermal inflammation. Affected inflammatory infiltrate included neutrophils, T cells, and plasma cells, with the predominantly affected cell types specific to the patient. Collectively, the broad activity of topical ruxolitinib on inflammatory signaling processes resulted in promising efficacy, even with heterogeneity in baseline inflammation, in this pilot cohort. Importantly, topical treatment not only resolved epidermal inflammation, but also cleared deeper inflammatory infiltrate. The efficacy ob