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

Tali Czarnowicki; Anders B. Dohlman; Kunal Malik; Diane Antonini; Robert Bissonnette; Tom C. Chan; Lisa Zhou; Huei Chi Wen; Yeriel Estrada; Hui Xu; Catherine Bryson; Jie Shen; Deepak Lala; Avi Ma'ayan; Gerard McGeehan; Richard Gregg; Emma Guttman-Yassky

doi:10.1016/j.anai.2018.03.013

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

Tali Czarnowicki
, Anders B. Dohlman
, Kunal Malik
, Diane Antonini
, Robert Bissonnette
, Tom C. Chan
, Lisa Zhou
, Huei Chi Wen
, Yeriel Estrada
, Hui Xu
, Catherine Bryson
, Jie Shen
, Deepak Lala
, Avi Ma'ayan
, Gerard McGeehan
, Richard Gregg
, Emma Guttman-Yassky

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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 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.

Original language	English
Pages (from-to)	631-640.e11
Journal	Annals of Allergy, Asthma and Immunology
Volume	120
Issue number	6
DOIs	https://doi.org/10.1016/j.anai.2018.03.013
State	Published - Jun 2018

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10.1016/j.anai.2018.03.013

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Czarnowicki, T., Dohlman, A. B., Malik, K., Antonini, D., Bissonnette, R., Chan, T. C., Zhou, L., Wen, H. C., Estrada, Y., Xu, H., Bryson, C., Shen, J., Lala, D., Ma'ayan, A., McGeehan, G., Gregg, R., & Guttman-Yassky, E. (2018). Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial. Annals of Allergy, Asthma and Immunology, 120(6), 631-640.e11. https://doi.org/10.1016/j.anai.2018.03.013

@article{f0f3e9ed6b6144dcb4ffd6f9baa1cb00,

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

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{\textendash}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.",

author = "Tali Czarnowicki and Dohlman, \{Anders B.\} and Kunal Malik and Diane Antonini and Robert Bissonnette and Chan, \{Tom C.\} and Lisa Zhou and Wen, \{Huei Chi\} and Yeriel Estrada and Hui Xu and Catherine Bryson and Jie Shen and Deepak Lala and Avi Ma'ayan and Gerard McGeehan and Richard Gregg and Emma Guttman-Yassky",

note = "Publisher Copyright: {\textcopyright} 2018 American College of Allergy, Asthma \& Immunology",

year = "2018",

month = jun,

doi = "10.1016/j.anai.2018.03.013",

language = "English",

volume = "120",

pages = "631--640.e11",

journal = "Annals of Allergy, Asthma and Immunology",

issn = "1081-1206",

publisher = "American College of Allergy, Asthma and Immunology",

number = "6",

}

Czarnowicki, T, Dohlman, AB, Malik, K, Antonini, D, Bissonnette, R, Chan, TC, Zhou, L, Wen, HC, Estrada, Y, Xu, H, Bryson, C, Shen, J, Lala, D, Ma'ayan, A, McGeehan, G, Gregg, R & Guttman-Yassky, E 2018, 'Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial', Annals of Allergy, Asthma and Immunology, vol. 120, no. 6, pp. 631-640.e11. https://doi.org/10.1016/j.anai.2018.03.013

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

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 -

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

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