Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up).

Background: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed.
Objective: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab.
Methods: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis.
Results: Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed.
Limitations: Open-label study design.
Conclusions: Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.
Competing Interests: Conflicts of interest Dr Blauvelt has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB. He has served as a scientific advisor (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, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor. He has been a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, and Merck. Dr Prajapati has served as an investigator for AbbVie, Amgen, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, UCB Pharma, and Valeant. He has served as a consultant, advisor and/or speaker for AbbVie, Actelion, Amgen, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, LEO Pharma, L’Oreal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB Pharma, and Valeant. Dr Laquer has received honoraria as a consultant from AbbVie, Allos, Aqua, Biogen, Celgene, Eli Lilly, Galderma, Intraderm, LEO Pharma, Mayne, Novartis, and Pfizer. She has served as an investigator for AbbVie, Aiviva, Amgen, Arcutis, Arena, Bellus, Biofrontera, Bristol Meyers Squibb, Cara, Dermavant, Forte, Galderma, Incyte, Kiniksa, Eli Lilly, LEO Pharma, Novan, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB. Dr Fischer has served as a principal investigator for AbbVie, UCB, and Eli Lilly. Dr Eisman has served on the Dermatology Advisory Alopecia Areata Board for Eli Lilly and is or has been an investigator in clinical trials for Pfizer Inc, AbbVie, Arena Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Botanix Pharmaceuticals, Dermira, Eli Lilly, Evelo Biosciences, Immunic Therapeutics, Jansen, Kobiolabs, Kymab Ltd, LEO Pharma, Novartis, TEVA Pharmaceuticals, Tigermed Pharmaceuticals, Suzhou Connect Biopharmaceuticals, and Regeneron Pharmaceuticals. Dr Eyerich has served as a speaker, investigator, and/or advisor for AbbVie, Almirall, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Hexal, Galapagos, Janssen, Eli Lilly, Pfizer, Novartis, Sanofi, and UCB Pharma. Drs Ladizinski, Hu, Wu, Calimlim, Kaplan, Y Liu, Teixeira, and J Liu are full-time employees of AbbVie and may hold AbbVie stock or stock options.
(Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)