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. 2025 Sep;15(9):2583-2594.
doi: 10.1007/s13555-025-01485-0. Epub 2025 Jul 14.

Achieving Optimal Treatment Targets and Minimal Disease Activity with Upadacitinib for Moderate-to-Severe Atopic Dermatitis: Integrated Analysis of Phase 3 Studies (Measure Up 1 and 2)

Jonathan I Silverberg  1 , Melinda Gooderham  2   3   4 , Norito Katoh  5 , Valeria Aoki  6 , Andrew E Pink  7 , Yousef Binamer  8 , Brad Glick  9 , Petra Staubach  10 , Brian Calimlim  11 , Chao Li  11 , Ayman Grada  11 , Alvaro Moreira  11 , Wan-Ju Lee  11 , Andreas Wollenberg  12   13   14
Affiliations

Achieving Optimal Treatment Targets and Minimal Disease Activity with Upadacitinib for Moderate-to-Severe Atopic Dermatitis: Integrated Analysis of Phase 3 Studies (Measure Up 1 and 2)

Jonathan I Silverberg et al. Dermatol Ther (Heidelb). 2025 Sep.

Abstract

Introduction: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) guidelines recommend achieving minimal disease activity (MDA) in atopic dermatitis (AD), defined as simultaneous achievement of optimal treatment targets for at least one clinician- and one patient-reported outcome (ClinRO + PRO). We assessed the effect of upadacitinib on achieving optimal ClinROs, optimal PROs, and MDA in Measure Up 1 (NCT03569293) and Measure Up 2 (NCT3607422) studies for patients with moderate to severe AD.

Methods: Patients were randomized to receive upadacitinib (15 mg or 30 mg) or placebo. Achievement of ≥ 1 optimal target in ClinROs, ≥ 1 optimal target in PROs, and MDA (≥ 1 optimal ClinROs and ≥ 1 optimal PROs) were reported at weeks 16 (upadacitinib vs placebo) and 52 (upadacitinib only). MDAs in selected combinations were also assessed at weeks 16 and 52. A total of 1683 and 1124 patients were included in the week 16 and 52 analysis, respectively.

Results: At week 16, a significantly higher proportion of patients receiving upadacitinib (15 mg: 42.5%, 30 mg: 55.9%) compared with placebo (6.4%) achieved MDA. At week 52, 57.4% and 69.9% of patients receiving 15 mg and 30 mg of upadacitinib achieved MDA, respectively. Specifically, patients receiving upadacitinib attained higher rates of ≥ 90% reduction from baseline in Eczema Area and Severity Index (EASI 90) + Worst Pruritus-Numerical Rating Scale (WP-NRS) 0/1 at week 16 (15 mg: 25.3%, 30 mg: 39.4% vs placebo: 1.8%) and maintained at week 52 (15 mg: 38.1%, 30 mg: 46.9%).

Conclusion: Treatment with upadacitinib achieved both ClinRO and PRO optimal treatment targets as well as MDA and may optimize overall disease management in patients with moderate-to-severe AD.

Trial registration: ClinicalTrials.gov NCT03607422 NCT03607422 NCT03607422.

Keywords: Atopic dermatitis; Clinician reported outcome; Minimal disease activity; Patient reported outcome; Quality of life; Upadacitinib.

Plain language summary

Patients with atopic dermatitis (AD) often suffer from skin symptoms such as itch, pain, and rash. These symptoms affect the patient’s sleep, mental health, and quality of life. Optimal treatment goals for AD have been established for skin severity assessments made by the doctor (ClinRO) and symptom and quality of life assessments made by the patient (PRO). Patients are said to have achieved minimal disease activity (MDA) when they achieve an optimal ClinRO treatment goal and an optimal PRO treatment goals. In this article, we report the results from two clinical trials (Measure Up 1 and 2) where patients received either upadacitinib (15 mg or 30 mg) or placebo for treatment of their AD. After 16 weeks, patients who took upadacitinib were more likely to achieve optimal ClinRO or PRO treatment goals and MDA compared to patients receiving placebo. Most patients receiving upadacitinib achieved optimal ClinRO or PRO treatment goals and MDA after 52 weeks of treatment. This study found that patients with AD experienced high levels of both skin improvement and symptom relief after 16 and 52 weeks of upadacitinib treatment.

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Conflict of interest statement

Declarations. Conflict of interest: Jonathan Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, Aldena, Aldena, Amgen, AObiome, Apollo, Arcutis, Arena, Asana, Aslan, Attovia, Bodewell, Boehringer-Ingelheim, Bristell-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, FIDE, Galderma, GlaxoSmithKline, Incyte, Inmagene, Invea, Kiniksa, Leo Pharma, Merck, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, TARGET-RWE, Teva, Triveni, Union, UpToDate; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly, Galderma, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Incyte, Pfizer. Valeria Aoki has served as an investigator in clinical trials (Sanofi, Amgen, Abbvie) and consultant/advisory board: Eli Lilly, Galderma, Abbvie. Yousef Binamer has received speaker honoraria for serving as a consultant for, and travel support from AbbVie, Eli Lilly, Janssen, Kyowa Kirin, NewBridge, Novartis, and Sanofi, and received research grants from Novartis and Sanofi. Brad Glick is an advisory board member, consultant, speaker and/or investigator for and received honoraria or grants from Amgen, AbbVie, AstraZeneca, Almirall, Acrutis, Bausch Health/Valeant, OrthoDermatologics, Boehringer Ingelheim, Bristol-Myers Squibb, Brickell Biotech, Cara Therapeutics, ChemoCentryx, Dermavant, Dermira, Eli Lilly, EPI/Novan Pharmaceuticals, Incyte, Janssen Pharmaceuticals, LEO Pharma, Galderma, Nimbus Lakshmi, Inc, Novartis Pharmaceutical Corporation, Sun Pharma, Pfizer, Sanofi, Regeneron, UCB Biopharmaceuticals and the CorEvitas AD, CorEvitas PSO and PROSE Registries. Dr. Glick is a shareholder of Top MD, LLC. Melinda Gooderham has been an investigator, speaker and/or advisor for: AbbVie, Acelyrin, Alumis, Amgen, Akros, Arcutis, Aristea, AnaptysBio, Apogee, Bausch Health, BMS, Boehringer Ingelheim, Cara, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, InMagene, JAMP Pharma, Janssen, LEO Pharma, L’Oreal, MedImmune, Meiji, Moonlake, Nektar, Nimbus, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, Union, Ventyx and Vyne. Norito Katoh has received honoraria as a speaker/consultant for Sanofi, Maruho, Abbvie, Eli Lilly Japan, Taiho Pharmaceutical, Pfizer, Mitsubishi Tanabe Pharma, Jansen Pharma, Kyowa Kirin, Celgene Japan, Torii Pharmaceutical, and Otsuka Pharmaceutical, and has received grants as an investigator from Mitsubishi Tanabe Pharma, Torii Pharmaceutical, Maruho, Sun Pharma, Boehringer Ingelheim Japan, Eisai, and Leo Pharma. Andrew Pink has acted as investigator, speaker, advisor, received educational support from, or received research support from AbbVie, Lilly, Pfizer, Sanofi, Leo, Galderma, Amgen, Novartis, J&J, BMS, BI, UCB, Almirall and Celgene. Petra Staubach-Renz has served as a speaker or advisor for AbbVie, Almirall, BMS, Boehringer Ingelheim, Janssen, Infectopharm, Leo, Lilly, Novartis, Pfizer, Sanofi, Galderma, Pierre Fabre, Klinge Pharma, Beiersdorf, L´Oreal, Galderma, Ichthyol, Incyte, Kalvista, Celltrion, Pharvaris, and Stadapharma. Andreas Wollenberg has served as an advisor or paid speaker for, or participated in clinical trials (with honoraria paid to the institution) sponsored by: AbbVie, Aileens, Almirall, Amgen, Apogee, Beiersdorf, Bioderma, Bioproject, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, DKSH, Eli Lilly, Galapagos, Galderma, Glenmark, GSK, Hans Karrer, Hexal, Incyte, Janssen-Cilag, Kyowa Kirin, Leo Pharma, L’Oreal, Maruho, MedImmune, MSD, Mylan, MSD, Nektar, Novartis, Pfizer, Pierre Fabre, Regeneron, Sandoz, Santen, Sanofi-Aventis and UCB. Brian Calimlim, Ayman Grada, Wan-Ju Lee, Chao Li, and Alvaro Moreira are full-time employees of AbbVie and may hold AbbVie stock or stock options. Ethical Approval: The original studies that collected the data analyzed within this manuscript were approved by the IRB, were conducted in accordance with the Declaration of Helsinki, and informed consent was obtained for participants.

Figures

Fig. 1
Fig. 1
Study design of Measure Up 1 and 2. aAged < 18 years. AD atopic dermatitis, EASI Eczema Area and Severity Index, BSA body surface area, JAK Janus kinase, NRS numeric rating scale, QD once daily, TCI topical calcineurin inhibitor, TCS topical corticosteroids, vIGA-AD Validated Investigator Global Assessment for Atopic Dermatitis. Previously published in Silverberg et al. Disease activity among patients with moderate‑to‑severe atopic dermatitis: results from phase 3 studies (Measure Up 1 and Measure Up 2) presented at AAD 2024
Fig. 2
Fig. 2
Achievement of optimal targets for at least one ClinRO, one PRO, and MDA. ***P < 0.001 vs placebo. Error bars represent 95% CI. ClinRO, clinician-reported outcome; MDA minimal disease activity, NRI-NC non-responder imputation with no special data handling for missing data due to COVID-19, OC observed cases, PBO placebo, PRO patient-reported outcome, UPA upadacitinib
Fig. 3
Fig. 3
MDA achievement with selected ClinRO and PRO optimal treatment targets. ***P < 0.001 vs placebo. Error bars represent 95% CI. IGA/BSA optimal treatment target IGA 0/1 and BSA ≤ 2%. BSA affected body surface area, DLQI Dermatology Life Quality Index, EASI 90 ≥ 90% improvement from baseline in the Eczema Area and Severity Index, IGA Investigator Global Assessment, NRI-NC non-responder imputation with no special data handling for missing data due to COVID-19, OC observed cases, PBO placebo, POEM patient-oriented eczema measure, SCORAD 75 ≥ 90% improvement from baseline in scoring atopic dermatitis score, UPA upadacitinib, WP-NRS worst pruritus numerical rating scale
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