Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis A randomized controlled trial

Background: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems. Objective: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD). Methods: A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and post-treatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated. Results: Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P =.02) and lipid (adenosine triphosphate-binding cassette subfamily Gmember 1 and sterol regulatory element binding protein 1c, P <.01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 non-significantly suppressed cellular infiltrates and down-regulated mRNA expression of several TH17/TH22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers. Conclusion: Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities. Trial Registration: clinicaltrials.gov Identifier: NCT02655679. (c) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.