Targeting the Aryl Hydrocarbon Receptor to Address the Challenges of Atopic Dermatitis

February 2024 | Volume 23 | Issue 2 | 23 | Copyright © February 2024


Published online January 18, 2024

Lawrence F. Eichenfield MDa,b, Jonathan I. Silverberg MD PhD MPHc, Adelaide A. Hebert MDd, Raj Chovatiya MD PhDe, Philip M. Brown MD JDf, Kimberly A. McHale PhDf, David S. Rubenstein MD PhDf, Anna M. Tallman PharmDf

aUniversity of California San Diego School of Medicine, San Diego, CA
bRady Children’s Hospital, San Diego, CA
cSchool of Medicine and Health Sciences, The George Washington University, Washington, DC
dUTHealth McGovern Medical School and Children’s Memorial Hermann Hospital, Houston, TX
eNorthwestern University Feinberg School of Medicine, Chicago, IL
fDermavant Sciences, Inc., Morrisville, NC

Eligible patients were permitted to enroll in ADORING 3 for a further 48 weeks of treatment based on their vIGA-ADTM score, whereby patients with a vIGA-ADTM score of 0 (clear) discontinue treatment and are monitored for remittive effect (maintaining a vIGA-ADTM score of 0 or 1 when off treatment).

CONCLUSION

AhR signaling has an important role in the regulation of skin health. Clinical trials with tapinarof, an AhR agonist, validate AhR as a therapeutic target for the treatment of inflammatory skin diseases. The targeting of transcription factors such as AhR represents a novel approach to AD therapy, distinct from treatments that target specific cytokines and enzymes.

Tapinarof cream acts locally at sites of application, with minimal-to-no systemic exposure. Tapinarof demonstrated efficacy and favorable tolerability in adults and adolescents with AD and is being evaluated in the ADORING trials in adults and children down to 2 years of age.

DISCLOSURES

L.F.E. has served as a consultant, advisor, or investigator for AbbVie, Almirall, Amgen, Arcutis, Arena, Aslan, Dermavant Sciences, Inc., Eli Lilly, Forte, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, and UCB Pharma. J.I.S. has received honoraria or grants, and/or has served as a consultant, advisory board member, or speaker for Afyx, Aobiome, Arena, Asana, BioMX, Bluefin Biomedicine, Bodewell, Boehringer Ingelheim, Celgene, Dermavant Sciences Inc., Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron, and Sanofi Genzyme. A.A.H. has received research support paid to the medical school from AbbVie, Arcutis, Dermavant Sciences Inc., and Pfizer; honoraria received from GSK, Sanofi Regeneron, and Ortho Dermatologics (as part of a Data Safety Monitoring Board); honoraria received from Dermavant Sciences, Inc., Incyte, LEO Pharma, Pfizer, Arcutis, Sun Pharma, Galderma, Novan, and Verrica. R.C. has served as an advisor, consultant, speaker, and/or investigator for AbbVie, Apogee, Arcutis, Argenx, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant Sciences, Inc., Eli Lilly and Company, Galderma, Genentech, Incyte, LEO Pharma, L'Oreal, Novan Inc., Pfizer Inc., Regeneron, Sanofi, and UCB Pharma. P.M.B., K.A.M., D.S.R., and A.M.T. are employees of Dermavant Sciences, Inc., with stock options.

Funding: Supported by Dermavant Sciences, Inc. Medical writing and editorial assistance were funded by Dermavant Sciences, Inc. 

ACKNOWLEDGMENT

Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom, UK, and was funded by Dermavant Sciences, Inc., in accordance with Good Publication Practice (GPP) guidelines (Ann Intern Med. 2022;175:1298-1304).

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