Abstract
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized. Objectives: Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate-to-severe AD and evaluate the kinetics of recovery on rescue treatment. Methods: Data from a phase 2b randomized, placebo-controlled trial (NCT02925117) of upadacitinib in patients with moderate-to-severe AD were analysed. Patients were randomized 1:1:1:1 to receive upadacitinib 7.5 mg, 15 mg, 30 mg or placebo, and then at Week 16, patients were re-randomized 1:1 to receive the same dose of upadacitinib (upadacitinib 30 mg for patients initialized to placebo) or placebo. From Week 20, those who experienced loss of response defined as Eczema Area and Severity Index <50% improvement from baseline (EASI 50) received rescue treatment with upadacitinib 30 mg. Results: Patients who withdrew from upadacitinib experienced a rapid loss of skin clearance response, while those who switched from placebo to upadacitinib gained response. Loss of skin clearance response occurred within 4 weeks and worsening of itch occurred within 5 days. In patients who originally received placebo or a lower dose of upadacitinib leading to a loss of EASI response, rescue treatment with upadacitinib 30 mg resulted in rapid recovery or improvement of both skin and itch responses; most patients who were re-randomized to placebo achieved EASI 75 and IGA 0/1 by 8 weeks of rescue treatment. No new safety risks were observed. Conclusions: Continuous treatment with upadacitinib is suggested to maintain skin clearance and antipruritic effects.
| Original language | English |
|---|---|
| Journal | Journal of the European Academy of Dermatology and Venereology |
| Volume | 37 |
| Issue number | 12 |
| Pages (from-to) | 2558-2568 |
| Number of pages | 11 |
| ISSN | 0926-9959 |
| DOIs | |
| Publication status | Published - 12.2023 |
Funding
EG‐Y is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Amgen, AnaptysBio, Aslan, Bristol‐Meyers Squibb, Boehringer Ingelheim, Cara Therapeutics, Concert, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, Pfizer, RAPT, Regeneron Pharmaceuticals, Sanofi and UCB. She is a consultant for AbbVie, Almirall, Amgen, Aslan Pharmaceuticals, AstraZeneca, Biolojic Design, Boehringer Ingelheim, Bristol‐Meyers Squibb, Cara Therapeutics, Connect Pharma, DBV Technologies, Eli Lilly, EMD Serono, Evidera, Galderma, Gate Bio, Genentech, Incyte, Inmagene, Janssen Biotech, Kyowa Kirin, LEO Pharma, Merck, Pfizer, Q32 Bio, RAPT Therapeutics, Regeneron, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB and Ventyx Biosciences. JIS has received honoraria as a consultant and/or advisory board member for AbbVie, Afyx, Aobiome, Arena, Asana, Aslan, BioMX, Biosion, Bluefin, Bodewell, Boehringer Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi‐Genzyme, Shaperon, Sidekick Health and Union. He has served as a speaker for AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi‐Genzyme and has received institutional grants from Galderma and Pfizer. DT is an advisor, speaker and/or consultant for AbbVie, Almirall, Amgen, Asana Biosciences, Biogen Idec, Boehringer Ingelheim, Bristol‐Myers Squibb, Janssen‐Cilag, Kyowa Kirin, LEO Pharma, Lilly, Merck Sharp & Dohme, Novartis, Regeneron, Sanofi‐Aventis, Pfizer and UCB. His institution received grants from LEO Pharma and Novartis. KAP is an advisor, speaker, consultant, steering committee member and/or researcher for AbbVie, Akros, Amgen, Anacor, Arcutis, Bausch Health (Valeant), Baxalta, Boehringer Ingelheim, Bristol‐Myers Squibb, Can‐Fite, Coherus, Dermira, Dow, Forward Pharma, Galderma, Genentech, Gilead, GlaxoSmithKline, InflaRx, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Meiji Seika Pharma, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi‐Genzyme, Takeda and UCB. SS is an investigator for Celldex, Clexio, Dermasence, Galderma, GSK, Incyte, Kiniksa, Novartis, Sanofi and Trevi Therapeutics. She is a consultant and/or member of advisory boards for AbbVie, Almirall, Beiersdorf, Benevolent, Bionorica, Cara Therapeutics, Celgene, Clexio Biosciences, DS Biopharma, Eli Lilly, Escient, Galderma, Grünenthal, Kiniksa, Klinge Pharma, Leo Pharma, Maruho, Menlo Therapeutics, P.G. Unna Academy, Perrigo, Pfizer, Sanofi, Symbio Research, Trevi Therapeutics, Vanda, Vifor and WebMD. LAB received honoraria as a consultant for Allakos, Arena Pharmaceuticals, DermTech, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Numab Therapeutics, Pfizer, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi‐Genzyme, Sanofi‐Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, Xencor and Yuhan Corp. She has received grants for clinical trials from AbbVie, Allakos, AstraZeneca, DermTech, Kiniksa, Pfizer, Regeneron, Ribon Therapeutics and Sanofi. She is a data monitoring committee member for Novartis. BK has served as a consultant for 23andMe, AbbVie, ABRAX Japan, Almirall, Amagma Therapeutics, Arcutis Biotherapeutics, Arena Pharmaceuticals, Argenx BV, AstraZeneca, Bellus Health, Blueprint Medicines, Boehringer Ingelheim, Bristol‐Myers Squibb, Cara Therapeutics, Clexio Biosciences, Cymabay Therapeutics, Daewoong Pharmaceutical, Eli Lilly, Escient Pharmaceuticals, Evommune, Galderma, Genentech, GlaxoSmithKline, Granular Therapeutics, Incyte Corporation, Janssen, Kiniksa, LEO Pharma, Maruho Company, Medicxi, Menlo Therapeutics, Novartis, OM Pharma, Pfizer, Recens Medical, Regeneron, Sanofi, Septerna, Third Harmonic, Trevi Therapeutics and Veradermics. He holds stock in ABRAX Japan, Locus Biosciences and Recens Medical. JPT is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals Coloplast, Eli Lilly, LEO Pharma, OM Pharma, Pfizer, Regeneron, Sanofi‐Genzyme and Union Therapeutics; a speaker for AbbVie, Almirall, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi‐Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi‐Genzyme. XH, JL, BMC, NV, JTC and HDT are full‐time employees of AbbVie Inc. and may own stock and/or stock options. AbbVie, Inc., and the authors thank all the trial investigators and the patients who participated in these clinical trials. AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing and approval of the publication. All authors had access to relevant data and participated in the drafting, review and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Spencer Hughes, PhD, of JB Ashtin and funded by AbbVie.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
- Centers: Center for Research on Inflammation of the Skin (CRIS)
DFG Research Classification Scheme
- 2.22-19 Dermatology
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