27862 Trifarotene transcriptomics analysis and acne-related gene expression

Abstract

Trifarotene cream, 0.005% is an FDA approved topical retinoid indicated for treatment of facial and truncal acne and has received positive outcome through the European Decentralized Procedure. Trifarotene is the first novel topical retinoid molecule approved for acne treatment in 20 years, and the only approved retinoid that specifically acts through retinoic acid receptor gamma. This study investigated new potential pathways through which trifarotene exerts its efficacy in acne by analyzing the changes in gene expression in the skin of acne patients. Subjects with moderate inflammatory acne of the back were treated with trifarotene 0.005% or vehicle cream on dedicated back areas for 27 days, and 4 biopsies were collected on each subject (non-involved skin, acne papule, trifarotene, and vehicle-treated site). Large-scale gene expression profiling of the biopsies was performed using Affymetrix technology, and treatment specific gene expression profiles were generated using statistical modeling. This analysis highlighted a specific gene expression profile, comprising of 67 genes uniquely driven by Trifarotene treatment with most of these genes known to affect immune responses as well as extracellular matrix reorganization. Interestingly, those genes were downregulated as compared with the papule signature suggesting that trifarotene reverses some inflammatory processes of the papule. Altogether, these results show that trifarotene has a unique action in acne treatment by acting on epidermal differentiation and proliferation (Aubert et al., 2018) as well as on innate and adaptive immune cells in acne pathogenesis.