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

Abstract

Background: Therapeutic options for mild hidradenitis suppurativa (HS) represent a significant gap in the current treatment landscape, with no U.S. Food and Drug Administration-approved therapies for early-stage HS. Topical Janus kinase (JAK) inhibitors (JAKi) are a compelling option due to the known upregulation of inflammatory JAK signalling in HS lesions and the recent success of systemic JAKi for the treatment of moderate-to-severe HS.

Objectives: To assess the clinical efficacy of ruxolitinib in a pilot cohort and to investigate the underlying biologic mechanisms associated with clinical response.

Methods: This was a pilot single-site open-label prospective 24-week clinical trial of topical ruxolitinib (NCT04414514). Men and women with mild HS (Hurley stage I or II), with active inflammatory nodules, were recruited. All participants were observed for 8 weeks to monitor lesion counts (observational phase); active therapy (treatment phase) was then administered for 16 weeks. Topical ruxolitinib 1.5% 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 taken at the start and end of treatment for downstream mechanistic RNA sequencing and histological analyses.

Results: Ten participants were enrolled in the study; four dropped out before the treatment phase of the trial. Six individuals with Hurley stage I (no tunnels) HS completed the study, five of whom successfully achieved Hidradenitis Suppurativa Clinical Response (HiSCR50) through 16 weeks of therapy. In this interim analysis, differential gene expression and gene set enrichment analyses revealed reduced activation of JAK-dependent interferon, interleukin (IL)-6, IL-2 and epidermal growth factor receptor signalling, and antimicrobial and keratinocyte responses. In contrast, signatures of wound healing and lipid metabolism were increased following JAKi treatment, indicating a return to 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.

Conclusions: Collectively, the broad activity of topical ruxolitinib on inflammatory signalling 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 observed efficacy provides rationale to further investigate topical JAKi and other novel topical treatments in HS.