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. 2024 May;14(5):1127-1144.
doi: 10.1007/s13555-024-01157-5. Epub 2024 May 2.

Upadacitinib Rapidly Improves Patient-Reported Outcomes in Atopic Dermatitis: 16-Week Results from Phase 3 Clinical Trials (Measure Up 1 and 2)

Eric L Simpson  1 , Vimal H Prajapati  2   3   4   5   6 , Yael A Leshem  7   8 , Raj Chovatiya  9   10 , Marjolein S de Bruin-Weller  11 , Sonja Ständer  12 , Andrew E Pink  13 , Brian M Calimlim  14 , Wan-Ju Lee  14 , Henrique Teixeira  14 , Barry Ladizinski  14 , Xiaofei Hu  14 , Yang Yang  14 , Yingyi Liu  14 , Meng Liu  14 , Ayman Grada  14 , Andrew M Platt  14 , Jonathan I Silverberg  15
Affiliations

Upadacitinib Rapidly Improves Patient-Reported Outcomes in Atopic Dermatitis: 16-Week Results from Phase 3 Clinical Trials (Measure Up 1 and 2)

Eric L Simpson et al. Dermatol Ther (Heidelb). 2024 May.

Abstract

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks.

Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment).

Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16.

Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD.

Trial registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422.

Keywords: Atopic dermatitis; Itch; Patient-reported outcome measures; Quality of life; Randomized controlled trials; Upadacitinib.

Plain language summary

Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients’ descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 1–2 weeks. The extent of the improvements increased through weeks 4–6 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis.

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Conflict of interest statement

Eric L. Simpson has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, ASLAN, Benevolent AI-Bio Tech Limited, BiomX Ltd, Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, Collective Acumen, Coronado, Dermira, Evidera, Excerpta Medica, Galderma, GSK, Forte Biosciences, Incyte Dermatologics, Janssen, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Lilly, Medscape, Merck, Novartis, Ortho Galderma, Pfizer, Physicians World, Pierre Fabre Dermo Cosmetique, Regeneron, Roivant Sciences, Sanofi-Genzyme, SPARC India, Trevi therapeutics, WebMD, and Valeant. He has received grants from AbbVie, Amgen, Arcutis, ASLAN, Castle Biosciences, Celgene, CorEvitas, Dermavant, Dermira, Galderma, Incyte, Kymab, Kyowa Hakko Kirin, LEO Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, and TARGET-DERM outside the submitted work. Vimal H. Prajapati has served as an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Cipher, Eczema Society of Canada, Galderma, GSK, Homeocan, Janssen, LEO Pharma, Lilly, L’Oréal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. He has served as an investigator for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Takeda, UCB, and Valeant. He has received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. Yael A. Leshem has received honoraria or fees as a consultant from AbbVie, Genentech, Janssen, Pfizer, and Sanofi. She has served as an advisory board member for AbbVie, Dexcel Pharma, Pfizer, Regeneron, and Sanofi; has received an independent research grant from AbbVie; and has, without personal compensation, provided investigator services for AbbVie, Lilly, and Pfizer. Raj Chovatiya has served as an advisor, consultant, speaker, and/or investigator for AbbVie, Arcutis, Argenx, Apogee, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Galderma, Genentech, Incyte, LEO Pharma, Lilly, L’Oréal, Nektar, Novan, Inc., Opsidio, Pfizer, Regeneron, Sanofi, and UCB. Marjolein S. de Bruin-Weller is a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Amgen, Aslan, Galderma, Janssen, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi-Genzyme. Sonja Ständer is an investigator for Celldex, Clexio, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, Menlo Therapeutics, Novartis, Sanofi Genzyme, and Trevi Therapeutics. She is a member of scientific advisory boards, consultant, and/or speakers’ bureaus for AbbVie, Almirall, Beiersdorf, Benevolent, Bionorica, Cara, Clexio Biosciences, Escient Pharmaceuticals, Galderma, Grünenthal, Kiniksa, Klinge Pharma, LEO Pharma, Lilly, Menlo Therapeutics, Pfizer, P.G. Unna Academy, Sanofi Genzyme, Symbio Research, Trevi Therapeutics, Vifor Pharma, and WebMD. Andrew E. Pink has been an advisor/speaker/investigator or has received educational support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, and UCB. Brian M. Calimlim, Wan-Ju Lee, Henrique Teixeira, Xiaofei Hu, Yang Yang, Yingyi Liu, Meng Liu, Ayman Grada, and Andrew M. Platt are full-time employees of AbbVie, and may hold AbbVie stock and/or stock options. Barry Ladizinski is a former employee of AbbVie and may hold AbbVie stock and/or stock options. He is a current employee of ONE Pharmaceuticals. Jonathan I. Silverberg receives consulting fees from AbbVie, Anacor Pharmaceuticals, GlaxoSmithKline, Lilly, Pfizer, Procter & Gamble, MedImmune, and Regeneron. He serves as an investigator in trials sponsored by Celgene, GlaxoSmithKline, Lilly, Regeneron, and Roche.

Figures

Fig. 1
Fig. 1
Patients enrolled in the Measure Up 1 and Measure Up 2 studies who achieved a WP-NRS improvement ≥ 4a and b WP-NRS 0/1b during the double-blind period (NRI-C). Comparisons at time points in shaded boxes were multiplicity controlled. *Nominal P < 0.05 versus placebo for all time points. **Multiplicity adjusted P < 0.001 versus placebo. aAssessed in patients with WP-NRS ≥ 4 at baseline. bAssessed in patients with WP-NRS > 1 at baseline. CI confidence interval, NRI-C non-responder imputation incorporating multiple imputation for missing data due to COVID-19, PBO placebo, UPA upadacitinib, WP-NRS Worst Pruritus Numerical Rating Scale
Fig. 2
Fig. 2
Patients enrolled in the Measure Up 1 and Measure Up 2 studies who achieved a ADerm-SS Skin Pain Improvement ≥ 4,a b ADerm-SS Skin Pain 0/1,b c ADerm-SS TSS-7 Improvement ≥ 28,c d ADerm-SS TSS-7 0–11,d e POEM Improvement ≥ 4,e and f POEM 0–2f during the double-blind period (NRI-C). Comparisons at time points in shaded boxes were multiplicity controlled. *Nominal P < 0.001 versus placebo for all time points. **Multiplicity adjusted P < 0.001 versus placebo. aAssessed in patients with ADerm-SS Skin Pain ≥ 4 at baseline. bAssessed in patients with ADerm-SS Skin Pain ≥ 2 at baseline. cAssessed in patients with ADerm-SS TSS-7 ≥ 28 at baseline. dAssessed in patients with ADerm-SS TSS-7 ≥ 12 at baseline. eAssessed in patients with POEM ≥ 4 at baseline. fAssessed in patients with POEM scores ≥ 3 at baseline. ADerm-SS Atopic Dermatitis Symptom Scale, CI confidence interval, NRI-C non-responder imputation incorporating multiple imputation for missing data due to COVID-19, PBO placebo, POEM Patient-Oriented Eczema Measure, TSS-7 7-item Total Symptom Score, UPA upadacitinib
Fig. 3
Fig. 3
Patients enrolled in the Measure Up 1 and Measure Up 2 studies who achieved a ADerm-IS Sleep Improvement ≥ 12a and b ADerm-IS Sleep 0–3b during the double-blind period (NRI-C). Comparison at time point in shaded box was multiplicity controlled. *Nominal P < 0.001 versus placebo for all time points. **Multiplicity adjusted P < 0.001 versus placebo. aAssessed in patients with ADerm-IS Sleep Domain ≥ 12 at baseline. bAssessed in patients with ADerm-IS Sleep Domain ≥ 4 at baseline. ADerm-IS Atopic Dermatitis Impact Scale, CI confidence interval, NRI-C non-responder imputation incorporating multiple imputation for missing data due to COVID-19, PBO placebo, UPA upadacitinib
Fig. 4
Fig. 4
Patients enrolled in the Measure Up 1 and Measure Up 2 studies who achieved a DLQI improvement scores ≥ 4,a b DLQI scores 0/1,b c ADerm-IS Daily Activities Improvement scores ≥ 14,c d ADerm-IS Daily Activities scores 0–2,d e ADerm-IS Emotional State Improvement scores ≥ 11,e and f ADerm-IS Emotional State scores 0–2f during the double-blind period (NRI-C). Comparisons at time points in shaded boxes were multiplicity controlled. *Nominal P < 0.001 versus placebo for all time points. **Multiplicity adjusted P < 0.001 versus placebo. aAssessed in patients with DLQI scores ≥ 4 at baseline. bAssessed in patients with DLQI scores > 1 at baseline. cAssessed in patients with ADerm-IS Daily Activities Domain scores ≥ 14 at baseline. dAssessed in patients with ADerm-IS Daily Activities Domain scores ≥ 3 at baseline. eAssessed in patients with ADerm-IS Emotional State Domain scores ≥ 11 at baseline. fAssessed in patients with ADerm-IS Emotional State Domain scores ≥ 3 at baseline. ADerm-IS Atopic Dermatitis Impact Scale, CI confidence interval, DLQI Dermatology Life Quality Index, NRI-C non-responder imputation incorporating multiple imputation for missing data due to COVID-19, PBO placebo, UPA upadacitinib
Fig. 5
Fig. 5
Overlap in achievement of WP-NRS 0/1, DLQI 0/1, and POEM 0–2 at week 16 for patients enrolled in the Measure Up 1 and Measure Up 2 studies. Data are reported as % (n). Percentages are calculated among patients who achieved at least one of the following endpoints at week 16: WP-NRS 0/1, DLQI 0/1, or POEM 0–2. Data from all treatment groups were combined. The analysis was based on observed cases, including only patients with non-missing data for all three outcome measures at week 16. DLQI Dermatology Life Quality Index, POEM Patient-Oriented Eczema Measure, WP-NRS Worst Pruritus Numerical Rating Scale
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