Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.
| Autor: | Czarnowicki T; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York., Dohlman AB; Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, BD2K-LINCS Data Coordination and Integration Center, Icahn School of Medicine at Mount Sinai School, New York, New York., Malik K; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; College of Medicine, SUNY Downstate, Brooklyn, New York., Antonini D; Vitae Pharmaceuticals Inc, an Allergan affiliate, Irvine, California., Bissonnette R; Innovaderm Research Inc, Montreal, Quebec, Canada., Chan TC; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Zhou L; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Wen HC; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Estrada Y; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Xu H; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Bryson C; Vitae Pharmaceuticals Inc, an Allergan affiliate, Irvine, California., Shen J; Allergan plc, Irvine, California., Lala D; Vitae Pharmaceuticals Inc, an Allergan affiliate, Irvine, California., Ma'ayan A; Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, BD2K-LINCS Data Coordination and Integration Center, Icahn School of Medicine at Mount Sinai School, New York, New York., McGeehan G; Vitae Pharmaceuticals Inc, an Allergan affiliate, Irvine, California., Gregg R; Vitae Pharmaceuticals Inc, an Allergan affiliate, Irvine, California., Guttman-Yassky E; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Electronic address: emma.guttman@mountsinai.org. |
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| Jazyk: | angličtina |
| Zdroj: | Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology [Ann Allergy Asthma Immunol] 2018 Jun; Vol. 120 (6), pp. 631-640.e11. Date of Electronic Publication: 2018 Mar 19. |
| DOI: | 10.1016/j.anai.2018.03.013 |
| Abstrakt: | 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 posttreatment 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 G member 1 and sterol regulatory element binding protein 1c, P < .01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several T 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. (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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