Armstrong, April

Bissonnette, Robert

Rubenstein, David S

Stein Gold, Linda F

Tallman, Anna M

English

Henry Ford Health System Scholarly Commons

Henry Ford Health System Henry Ford Health System Scholarly Commons Dermatology Articles Dermatology 3-4-2021 Folliculitis with tapinarof, when it occurs, is generally mild, self-limiting, and rarely interferes with therapy Robert Bissonnette Linda F. Stein Gold David S. Rubenstein Anna M. Tallman April Armstrong Follow this and additional works at: https://scholarlycommons.henryford.com/dermatology_articles JAAD ONLINE: NOTES & COMMENTSTapinarof-associated folliculitis isgenerally mild, self-limiting, andrarely interferes with therapyTo the Editor: We thank Konstantinou et al1 for theirinterest in our article on the mechanism of action oftapinarof. We appreciate the opportunity to clarifyand share information on folliculitis observed intapinarof clinical trials, as this is completely differentfrom dioxin-induced chloracne or hidradenitissuppurativa.Konstantinou et al1 draw associations betweentapinarof and dioxin-like compounds based on theiraryl hydrocarbon receptor (AhR)-binding activity.However, since AhR is a ligand-dependenttranscription factor, any downstream effects arehighly dependent on the molecule to which it binds.Therefore, the mechanisms underlying the efficacyand safety of tapinarof in psoriasis are distinct fromdioxins and other AhR-binding ligands.Tapinarof is a naturally identified topicaltherapeutic AhR modulating agent, thus differentfrom pathologic AhR modulating agents, such as themanmade toxin, dioxin. Tapinarof and dioxins bindat distinctly different sites on the AhR complex,modulate different genes and pathways, and causevastly different downstream effects.2,3 Moreover,tapinarof has limited systemic exposure asdemonstrated by maximal use pharmacokineticstudies.4Information on folliculitis has been obtained frommore than 2200 patients in 18 tapinarof clinical trials.Across all trials, the incidence, morphology, andseverity of folliculitis have remained consistent. Inthe most recent, pivotal, phase 3 psoriasis trials in1025 patients,3 the adverse event associated withtapinarof was folliculitis, which was mostly mild,resulted in a low incidence of study discontinuation(\1.8%), was localized to the hair follicle, and wasnot associated with a higher frequency in areasprone to acne. Therefore, localized folliculitis inthese studies was not analogous to hidradenitissuppurativa5 or the lesions seen in chloracne, whichinvolve the sebaceous glands. Sebaceous glandatrophy has never been observed with tapinarof inany preclinical in vivo studies, regardless of the routeof delivery, including chronic exposure.In summary, evidence with tapinarof is notsupportive of the associations proposed byKonstantinou et al,1 and the clinical data demon-strates that tapinarof-associated folliculitis is generallymild, self-limiting, and rarely interferes with therapy.Robert Bissonnette, MD,a Linda Stein Gold, MD,bDavid S. Rubenstein, MD, PhD,c Anna M. Tall-man, PharmD,d and April W. Armstrong, MD,MPHeFrom the Innovaderm Research Inc, Montreal,Quebec, Canada,a Henry Ford Health System,Detroit, Michigan,b Dermavant Sciences, Inc,Durham, North Carolina,c Dermavant SciencesInc, Long Beach, California,d and Keck School ofMedicine of the University of SouthernCalifornia, Los Angeles, California.eFunding sources: Editorial and medical writingsupport under the guidance of the authors wasprovided by ApotheCom, UK, and was funded byDermavant Sciences, Inc in accordance withGood Publication Practice (GPP3) guidelines(Ann Intern Med. 2015;163:461e464).IRB approval status: Not applicable.Reprints not available from the authors.Correspondence to: Robert Bissonnette, MD,Innovaderm Research, 3530 St-Laurent, Suite300, Montreal, QC H2X 2V1, CanadaE-mail: rbissonnette@innovaderm.comConflicts of interestDr Bissonnette is a consultant with honoraria for BauschHealth Companies Inc and Boston Pharmaceuticals; aninvestigator with grants/research funding for AbbVie Incand Escalier Biosciences, Inc; an advisor with honoraria andan investigator with grants/research funding for BMS,Boehringer Ingelheim, Eli Lilly and Company, and PfizerInc; a consultant with honoraria and an investigator withgrants/research funding for Janssen-Ortho Inc, SiennaBiopharmaceuticals, Inc, and Valeant PharmaceuticalsNorth America LLC; and an advisor, a consultant withhonoraria, and an investigator with grants/research fundingfor Dermavant Sciences, Inc.Dr Gold is an investigator, consultant, and speaker withhonorarium for Leo Pharma; an investigator with honorar-ium for Incyte; a consultant and speaker with honorariumfor Mayne Pharma and Taro Pharmaceutical Industries; aninvestigator and consultant for Ortho Dermatologics andSun; and a consultant with honorarium and an investigatorfor Dermavant Sciences, Inc.Dr Rubenstein is an employee of Dermavant Sciences,Inc with stock options.Dr Tallman is an employee of Dermavant Sciences, Incwith stock options.Dr Armstrong has served as a research investigator orscientific advisor to AbbVie, BI, BMS, EPI, Incyte, Leo,UCB, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun,J AM ACAD DERMATOL n 2021 e1Dermavant Sciences, Inc, Dermira, Sanofi, Regeneron,Pfizer, and Modmed.REFERENCES1. Konstantinou MP, Jendoubi F, Hegazy S, et al. Tapinarof-in-duced folliculitis: the paradigm of activation of the arylhydrocarbon signaling pathway. J Am Acad Dermatol. 2021Mar 4;S0190-9622(21)00486-2.2. Smith S, McHale K, Creech K, et al. Differential ligand bindingdistinguishes therapeutic from pathologic aryl hydrocarbonreceptor (AhR) modulating agents: implications for inflamma-tory skin disease. J Infect Dis. 2020;140:581-595.3. Lebwohl M, Stein Gold L, Strober B, et al. Tapinarof cream 1%QD for the treatment of plaque psoriasis: efficacy and safety intwo pivotal phase 3 trials. J Skin. 2020;4(6):s75.4. Jett J, McLaughlin M, Lee M, et al. Maximal use study oftapinarof cream 1% in subjects with extensive plaque psori-asis. J Skin. 2020;4(6):s74.5. Alikhan A, Sayed C, Alavi A, et al. North American clinicalmanagement guidelines for hidradenitis suppurativa: a pub-lication from the United States and Canadian HidradenitisSuppurativa Foundations: part I: diagnosis, evaluation, and theuse of complementary and procedural management. J AmAcad Dermatol. 2019;81(1):76-90.https://doi.org/10.1016/j.jaad.2021.03.006J AM ACAD DERMATOLn 2021e2 Notes & Comments

Folliculitis with tapinarof, when it occurs, is generally mild, self-limiting, and rarely interferes with therapy

https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?article=1553&context=dermatology_articles

Folliculitis with tapinarof, when it occurs, is generally mild, self-limiting, and rarely interferes with therapy

Abstract

Similar works

Full text

Available Versions

Henry Ford Health System Scholarly Commons