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

Ann Allergy Asthma Immunol. 2018 Jun;120(6):631-640.e11. doi: 10.1016/j.anai.2018.03.013. Epub 2018 Mar 19.

Abstract

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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / immunology
  • Administration, Cutaneous
  • Adult
  • Anti-Inflammatory Agents / therapeutic use*
  • Biological Transport / drug effects
  • Biological Transport / immunology
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Double-Blind Method
  • Epidermis / drug effects*
  • Epidermis / immunology
  • Epidermis / pathology
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Immunologic Factors / therapeutic use*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / immunology
  • Keratin-16 / genetics
  • Keratin-16 / immunology
  • Liver X Receptors / agonists*
  • Liver X Receptors / genetics
  • Liver X Receptors / immunology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Middle Aged
  • RNA, Messenger / agonists*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • S100A12 Protein / genetics
  • S100A12 Protein / immunology
  • Severity of Illness Index
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / immunology
  • Treatment Outcome

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Inflammatory Agents
  • IL6 protein, human
  • Immunologic Factors
  • Interleukin-6
  • Intermediate Filament Proteins
  • KRT16 protein, human
  • Keratin-16
  • Liver X Receptors
  • Membrane Proteins
  • RNA, Messenger
  • S100A12 Protein
  • S100A12 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • filaggrin
  • loricrin

Associated data

  • ClinicalTrials.gov/NCT02655679