Funding

The ECZTRA 1 and 2 clinical trials were sponsored by LEO Pharma A/S (Ballerup, Denmark).

Conflict of Interest

Eric L. Simpson reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Benevolent AI Bio Limited ‘BAI’, BiomX Ltd, Bluefin Biomedicine Inc, Boehringer-Ingelheim, Boston Consulting Group, Collective Acumen, LLC (CA), Coronado, Dermira, Eli Lilly, Evidera, ExcerptaMedica, Galderma, GlaxoSmithKline, Forte Bio RX, Incyte Dermatologics, Janssen, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Medscape LLC, Merck, Novartis, Ortho Galderma, Pfizer, Physicians World LLC, Pierre Fabre Dermo Cosmetique, Regeneron, Roivant, Sanofi-Genzyme, SPARC India, Trevi Therapeutics, WebMD and Valeant; and reports grants (or served as Principal Investigator role) from AbbVie, Amgen, Arcutis, Aslan, Castle Biosciences, Inc., Celegene, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Kymab, Kyowa Hakko Kirin, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, and TARGET-DERM. Andrew E. Pink reports personal fees and non-financial support from LEO Pharma, Novartis, and UCB; and personal fees from AbbVie, Almirall, Amgen, BMS, Boehringer Ingelheim, Janssen, La Roche-Posay, Lilly, Pfizer, and Sanofi. Andrew Blauvelt has served as a speaker (received honoraria) for AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, and Sanofi; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Melinda Gooderham has been an investigator, speaker, and/or advisor for AbbVie, Amgen, Akros, AnaptysBio, Aslan, Arcutis, Aristea, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Meiji, Moonlake, Nimbus, Novartis, Pfizer, Reistone, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, and UCB. April W. Armstrong has received research grants and personal fees from Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, and Novartis; received personal fees from Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; and receivedgrants from Dermira, Kyowa Hakko Kirin, and UCB. Margitta Worm reports grants or contracts from ALK-Abelló Arzneimittel GmbH and Mylan Germany GmbH; consulting fees from Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, and Regeneron Pharmaceuticals, Inc.; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ALK-Abelló Arzneimittel GmbH, Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Actelion Pharmaceuticals Deutschland GmbH, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, and Aimmune Therapeutics UK Limited; support for attending meetings and/or travel from Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc; and participation on a Data Safety Monitoring Board or Advisory Board for Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, and Regeneron Pharmaceuticals, Inc. Norito Katoh has received honoraria as a speaker/consultant for Sanofi, Maruho, Abbvie, Ely-Lilly Japan, Taiho Pharmaceutical, Jansen Pharma, Mitsubishi Tanabe Pharma, Abbvie, Kyowa Kirin, Celgene Japan, and LEO Pharma; and has received grants as an investigator from Sanofi, Maruho, Abbvie, Mitsubishi Tanabe Pharma, Ely-Lilly Japan, Kyowa Kirin, Sun Pharma, Taiho Pharmaceutical, and LEO Pharma. Ketty Peris reports grants or personal fees for participation in advisory boards from AbbVie, Almirall, Galderma, Lilly, LEO Pharma, Novartis, Pierre Fabre, Sanofi, Sun Pharma, and Janssen. Luis Puig has received consultancy/speaker’s honoraria from, and/or participated in clinical trials sponsored by, AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, LEO Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB. Sébastien Barbarot is an investigator or speaker for AbbVie, Almirall, Chiesi, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi-Genzyme, and UCB Pharma. Thomas Mark was an employee and stockholder of LEO Pharma A/S when conducting the data analyses for this publication. Ann-Marie Tindberg and Louise Abildgaard Steffensen are employees of LEO Pharma A/S. Andreas Wollenberg has received grants, personal fees, or non-financial support from AbbVie, Almirall, Beiersdorf, Bioderma, BMS, Chugai, Galapagos, Galderma, Glenmark, GSK, Hans Karrer, LEO Pharma, Lilly, L’Oreal, Maruho, MedImmune, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis.

Data Availability

Data will be made available upon request to the study sponsor, following review by the external Patient and Scientific Review Board.

Ethics Approval

The ECZTRA 1 and 2 trials were sponsored by LEO Pharma A/S (Ballerup, Denmark) and conducted in accordance with the ethical principles derived from international guidelines, including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, and in compliance with International Council for Harmonisation guidelines for Good Clinical Practice. The clinical trial was approved by Institutional Review Boards or Ethics Committees at each study site. This trial followed the Consolidated Standards of Reporting Trials reporting guideline.

Consent to Participate

All patients provided written informed consent.

Consent for Publication

Not applicable.

Code Availability

Not applicable.

Author Contributions

Conceptualization: All authors contributed equally. Investigation: All authors contributed equally. Data curation: Thomas Mark (lead). Formal analysis: Thomas Mark (lead), Ann-Marie Tindberg (supporting). Methodology: Thomas Mark (equal), Ann-Marie Tindberg (equal). Visualization: Ann-Marie Tindberg (lead). Writing: All authors contributed equally. Review/editing: All authors contributed equally. All authors read and approved the final version of the manuscript.