TY - JOUR
T1 - Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis
T2 - A randomized controlled trial
AU - Czarnowicki, Tali
AU - Dohlman, Anders B.
AU - Malik, Kunal
AU - Antonini, Diane
AU - Bissonnette, Robert
AU - Chan, Tom C.
AU - Zhou, Lisa
AU - Wen, Huei Chi
AU - Estrada, Yeriel
AU - Xu, Hui
AU - Bryson, Catherine
AU - Shen, Jie
AU - Lala, Deepak
AU - Ma'ayan, Avi
AU - McGeehan, Gerard
AU - Gregg, Richard
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2018 American College of Allergy, Asthma & Immunology
PY - 2018/6
Y1 - 2018/6
N2 - 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 H 17/T H 22-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.
AB - 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 H 17/T H 22-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.
UR - https://www.scopus.com/pages/publications/85048098486
U2 - 10.1016/j.anai.2018.03.013
DO - 10.1016/j.anai.2018.03.013
M3 - Article
C2 - 29567358
AN - SCOPUS:85048098486
SN - 1081-1206
VL - 120
SP - 631-640.e11
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 6
ER -