Skin clearance, duration of treatment-free interval, and safety of tapinarof cream 1% once daily: Results from ADORING 3, a 48-week phase 3 open-label extension trial in adults and children down to 2 years of age with atopic dermatitis
- PMID: 40383273
- DOI: 10.1016/j.jaad.2025.05.1391
Skin clearance, duration of treatment-free interval, and safety of tapinarof cream 1% once daily: Results from ADORING 3, a 48-week phase 3 open-label extension trial in adults and children down to 2 years of age with atopic dermatitis
Abstract
Background: In 2 pivotal phase 3 trials, tapinarof demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis.
Objective: Assess skin clearance rates, duration of treatment-free intervals, and safety of tapinarof in a phase 3 open-label extension trial.
Methods: Patients from the ADORING 1 and 2 pivotal phase 3 trials, a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients received tapinarof for up to 48 weeks. Treatment was based on Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score. Patients with vIGA-AD≥1 received tapinarof until vIGA-AD=0. Patients achieving vIGA-AD=0 discontinued tapinarof and were monitored for treatment-free interval. Patients with vIGA-AD≥2 were re-treated until vIGA-AD=0.
Results: Seven hundred twenty-eight patients enrolled. Overall, 51.9% achieved vIGA-AD=0, and 81.6% achieved vIGA-AD=0 or 1 at least once. After first achieving complete clearance and discontinuing treatment, the mean first treatment-free interval was 79.8 consecutive days. Tapinarof was well tolerated, with no new safety signals. Most-frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%).
Limitations: Open-label; treatment-free interval potentially underestimated.
Conclusion: Tapinarof was well tolerated and resulted in high skin clearance rates that were maintained off-therapy and consistent safety in patients down to age 2 years.
Keywords: aryl hydrocarbon receptor agonist; atopic dermatitis; complete clearance; long-term efficacy; long-term extension trial; remittive effect; tapinarof cream 1% once daily; treatment-free interval.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflicts of interest Dr Bissonnette is an advisory board member, consultant, speaker, and/or investigator for and received honoraria and/or grants from AbbVie, Alumis, Amgen, Arcutis, Bausch Health, Bristol Myers Squibb/Celgene, Boston Pharma, Dermavant Sciences, Inc, Eli Lilly, Janssen, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, UCB Pharma, VentyxBio, Xencor, and Zai Lab. He is also an employee and shareholder of Innovaderm Research Inc. Dr Gold has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from Amgen, Arcutis, Bristol Myers Squibb, Dermavant Sciences, Inc, Eli Lilly, LEO Pharma, Ortho Dermatologics, Pfizer, and UCB Biopharma. Dr Kircik has served as a consultant, speaker, investigator, or advisory board member for Abbott Laboratories, AbbVie, Ablynx, Aclaris, Acambis, Allergan, Inc, Almirall, Amgen, Inc, Anacor Pharmaceuticals, AnaptysBio, Arcutis Biotherapeutics, Arena Pharmaceuticals, Assos Pharmaceuticals, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Bausch Health, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biogen Idec, BioLife, Biopelle, Bristol Myers Squibb, Boehringer Ingelheim, Breckenridge Pharma, Cassiopea SpA, Centocor, Inc, Cellceutix, Cipher Pharmaceuticals, Coherus BioSciences, Colbar LifeScience, Combinatrix, Connetics Corporation, Coria Laboratories, Dermavant Sciences, Inc, Dermira, Dermik Laboratories, Dow Pharmaceutical Sciences, Inc, Dr Reddy's Laboratories, DUSA Pharmaceuticals, Embil Pharmaceutical Co. Ltd, Eli Lilly, EOS, Exeltis, Ferndale Laboratories, Inc, Ferrer, Foamix Pharmaceuticals, Galderma, Genentech, Inc, GlaxoSmithKline, Glenmark Pharmaceuticals, Healthpoint, Ltd, Idera Pharmaceuticals, Incyte, Intendis, Innocutis, Innovail, ISDIN, Johnson & Johnson, Kyowa Kirin, Laboratory Skin Care Inc, LEO Pharma, L’Oréal, 3M, Maruho Co, Ltd, Medical International Technologies, Merck, Medicis Pharmaceutical Corp, Merz Pharma, NanoBio, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals Corp, Obagi, Onset Dermatologics, Ortho Neutrogena, Pediapharma, Pfizer, Promius Pharma, PuraCap, Pharmaderm, QLT, Inc, Quinnova Pharmaceuticals, Quatrix, Regeneron, Sanofi, Serono (Merck Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Sun Pharma, Taro Pharmaceutical Industries, Toler Rx, Triax Pharmaceuticals, UCB Pharma, Valeant Pharmaceuticals Intl, Warner Chilcott, XenoPort, and ZAGE. Dr Simpson reports grants and fees for participation as a consultant and principal investigator from Eli Lilly and Company, LEO Pharma, Pfizer, and Regeneron; grants for participation as a principal investigator from Galderma and Merck & Co, Inc; and fees for consultant services from AbbVie and Boehringer Ingelheim. Dr Eichenfield has served as a consultant, advisor, or investigator for AbbVie, Amgen, Apogee, Arcutis, Aslan, Bausch, Bristol Myers Squib, Castle Biosciences, Dermavant Sciences, Inc, Eli Lilly, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, and UCB Pharma. Dr Browning has served as an investigator for AbbVie, Acelyrin, Amgen, Arcutis, Dermavant Sciences, Inc, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, UCB Pharma, and Vyne; and as a speaker for Krystal, Pfizer, and Regeneron. Dr Hebert has received research support paid to the medical school from AbbVie, Arcutis, Dermavant Sciences, Inc, and Pfizer; has received honoraria from Arcutis, Dermavant Sciences, Inc, Galderma, Incyte, LEO Pharma, Novan, Ortho Dermatologics, Sun Pharma, and Verrica; and has received honoraria as part of Data Safety Monitoring Boards for Alphyn, GSK, Ortho Dermatologics, and Sanofi-Regeneron. Dr Alexis has served as a consultant, speaker, or advisory board member for AbbVie, Aerolase, Allergan, Almirall, Alphyn, Amgen, Apogee, Arcutis, Avita Medical, Bausch Health, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Canfield, Cara, Castle, Cutera, Dermavant Sciences, Inc, Eli Lilly, EPI Health Inc, Galderma, Genentech, Incyte, Janssen, Johnson & Johnson, L’Oréal, LEO Pharma, Ortho, Pfizer, Regeneron, Sanofi-Genzyme, Sanofi-Regeneron, Swiss American, UCB Biopharma, and VisualDx; has received grants to his institution from AbbVie, Amgen, Arcutis, Castle, Dermavant Sciences, Inc, Galderma, Incyte, and LEO Pharma; royalties from Elsevier, Springer, Wiley-Blackwell, and Wolters Kluwer Health; and equipment from Aerolase. Dr Soong has served as a consultant, speaker, investigator, or advisory board member for AbbVie, Allakos, Amgen, Aslan, AstraZeneca, Celldex, Dermavant Sciences, Inc, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Glenmark, Incyte, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, and UCB Biopharma. Drs Tallman and Brown are employees of Dermavant Sciences, an Organon Company. Drs Piscitelli and Rubenstein are former employees of Dermavant Sciences, Inc. Dr Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant Sciences, Inc, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, TARGET-RWE, Union, and UpToDate; speaker for AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and his institution has received grants from Galderma, Incyte, and Pfizer.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
