Hidradenitis Suppurativa and Comorbid Disorder Biomarkers, Druggable Genes, New Drugs and Drug Repurposing—A Molecular Meta-Analysis

Abstract

Chronic inflammation and dysregulated epithelial differentiation, especially of hair follicle keratinocytes, have been suggested as the major pathogenetic pathways of hidradenitis suppurativa/acne inversa (HS). On the other hand, obesity and metabolic syndrome have additionally been considered as an important risk factor. With adalimumab, a drug has already been approved and numerous other compounds are in advanced-stage clinical studies. A systematic review was conducted to detect and corroborate HS pathogenetic mechanisms at the molecular level and identify HS molecular markers. The obtained data were used to confirm studied and off-label administered drugs and to identify additional compounds for drug repurposing. A robust, strongly associated group of HS biomarkers was detected. The triad of HS pathogenesis, namely upregulated inflammation, altered epithelial differentiation and dysregulated metabolism/hormone signaling was confirmed, the molecular association of HS with certain comorbid disorders, such as inflammatory bowel disease, arthritis, type I diabetes mellitus and lipids/atherosclerosis/adipogenesis was verified and common biomarkers were identified. The molecular suitability of compounds in clinical studies was confirmed and 31 potential HS repurposing drugs, among them 10 drugs already launched for other disorders, were detected. This systematic review provides evidence for the importance of molecular studies to advance the knowledge regarding pathogenesis, future treatment and biomarker-supported clinical course follow-up in HS.

Pharmacological interventions for hidradenitis suppurativa: a protocol for systematic review and network meta-analysis of randomised trials and non-randomised studies

“… 45 Recent advances in genetic and pharmacological research have identified many new potential HS-associated genes, suggesting that more classes of drugs can be used in HS treatments. 46 Landmark trials, such as the PIONEER I and II—phase 3 trials, have solidified recommendations of pharmacological therapy, that is, the use of adalimumab as a mainstay treatment for refractory HS cases. 12 17 47 Therefore, exploring pharmacological treatment in severe HS cases as a solution alternative to surgery seems worthy of consideration.…”

Molecular analysis of inflammatory diseases

“…Finally, two initiatives are worth to be mentioned; the first one is brightly described in the article of Zouboulis et al 37 It revises through an extensive Metaanalysis, the integrated relationships between Hidradenitis suppurativa related genes, transcriptomes and the available drugs including the most recent and advanced ones. The second one is the very recent bioinformatic pipeline, employing variant enrichment analysis (VEA) to identify common disrupted pathways in PASH and PAPASH patients, simply using WES data 32 .…”

“…Finally, two initiatives are worth to be mentioned; the first one is brightly described in the article of Zouboulis et al 37 It revises through an extensive Metaanalysis, the integrated relationships between Hidradenitis suppurativa related genes, transcriptomes and the available drugs including the most recent and advanced ones.…”

Registries, multicentre and genome‐wide association studies in hidradenitis suppurativa

“…Several factors enable nowadays GWAS, namely (a) the existence of biobanks, (b) the international HapMap Project (identification of common SNPs) and (c) the development of genotyping arrays 25,26 . Current studies have detected both differential gene expression and differential protein topography in HS 27,28 …”

“…25,26 Current studies have detected both differential gene expression and differential protein topography in HS. 27,28 The EHSF e.V. plans in cooperation with a third industry party…”