FUNDING AND DISCLOSURESAbbVie funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. No honoraria or payments were made for authorship.

J.I. Silverberg received honoraria for advisory board, speaker, and consultantservices from AbbVie, Asana, Bluefin, Boehringer Ingelheim, Celgene, Dermavant,Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, LeoPharma, Novartis, Pfizer, Regeneron, and Sanofi; and research grants forinvestigator services from Galderma.

J.P. Thyssen is an advisor, investigator, and speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

D. Rosmarin has received consulting fees, personal fees, and / or fees for speakingfrom Pfizer, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene,Dermavant, Dermira, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Novartis, Regeneron,Sanofi, Sun Pharma, UCB, and VielaBio; and has received grants / researchfunding from Galderma and Merck.

A.E. Pink has given talks or consulted for Sanofi, Novartis, Almirall, Leo Pharma, Eli Lilly, AbbVie, La Roche-Posay, Pfizer, Janssen, and UCB.

B.M. Calimlim, H.D. Teixeira, X. Hu, and Y. Yang are employees of AbbVie andmay own AbbVie stock or stock options.

D. Thaçi has acted as consultant, member of scientific advisory boards, or lecturerfor AbbVie, Almirall, Amgen, Biogen-Idec, Bristol Myers Squibb, BoehringerIngelheim, Celgene, Eli Lilly, Galapagos, Janssen-Cilag, Leo Pharma, Morphosis,Novartis, Pfizer, La Roche-Posay, Regeneron, Sandoz-Hexal, Sanofi, and UCB;and has received grants or research support from Celgene, Leo Pharma,and Novartis.

Presented at the 2021 Revolutionizing Atopic Dermatitis (RAD) Virtual Conference, June 13, 2021

Effects of Upadacitinib on Patient-Reported Symptoms of Atopic Dermatitis: Atopic Dermatitis Symptom Scale (ADerm-SS) Results From Two Pivotal Phase 3 Studies (Measure Up 1 and Measure Up 2)Jonathan I Silverberg1, Jacob P Thyssen2, David Rosmarin3, Andrew E Pink4, Brian M Calimlim5, Henrique D Teixeira5, Xiaofei Hu5, Yang Yang5, Diamant Thaçi6 1Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington DC, USA; 2Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; 3Department of Dermatology, Tufts Medical Center, Boston, Massachusetts, USA; 4St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom; 5AbbVie Inc., North Chicago, Illinois, USA, 6Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany

BACKGROUND• Atopic dermatitis (AD) is a chronic, inflammatory skin disease that is associated

with intense itch, dryness, skin pain, and multiple skin manifestations. Thesesymptoms significantly impact patients’ quality of life and daily functioning.Assessing how a therapy effects the way patients feel and function is essential.1

• Systemic therapy is warranted in patients with moderate to severe AD and aninadequate response to topical therapy, such as corticosteroids and calcineurininhibitors1-2

• Currently, few systemic agents are approved for AD and many are not suitable forlong-term use. Thus, there is an unmet need for patients with inadequateresponses to topical agents.3

• Upadacitinib (UPA), a selective and orally available Janus kinase-1 (JAK-1)inhibitor, was shown to statistically significantly reduce disease severity ascompared with placebo in patients with AD through 16 weeks of treatment4-6

• To better understand treatment efficacy of patient symptoms, the impact of UPA onpatient-reported symptoms after 16 weeks of treatment was assessed using theAtopic Dermatitis Symptom Scale (ADerm-SS), a novel patient-reportedinstrument7

OBJECTIVE• To assess the effects of UPA on patient-reported symptom burden in

adolescent and adult patients with moderate to severe AD compared withplacebo in two monotherapy Phase 3 clinical trials (Measure Up 1 andMeasure Up 2)

METHODSSTUDY DESIGN AND PARTICIPANTS• Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) are ongoing

randomized, Phase 3, double-blind, placebo-controlled, multicenter studiesevaluating UPA in adolescents (aged 12–17 years) and adults (aged 18 – 75years) with moderate to severe AD. The study design, key inclusion / exclusioncriteria, and coprimary endpoints are illustrated in Figure 1

Figure 1. Study Design of Measure Up 1 and Measure Up 2

Patients received oral study treatment (upadacitinib 30 mg, upadacitinib 15 mg, or placebo) once daily. aData reported here are from the double-blind treatment period. bThe blinded extension period is ongoing. AD, atopic dermatitis; BSA: body surface area; EASI, eczema area and severity index; JAK, Janus kinase; mg, milligrams per day; NRS, numerical rating scale; vIGA-AD, Validated Investigator Global Assessment for Atopic Dermatitis.

ATOPIC DERMATITIS SYMPTOM SCALE (ADERM-SS) SCORING PARADIGM• The ADerm-SS is a novel, content-valid patient-reported outcome (PRO)

questionnaire composed of 11 items, each scored 0–10, with higher scoresindicating worsening symptoms7

• The 11 items assessed by the ADerm-SS are key symptoms of moderate tosevere AD that affect quality of life and daily functioning. By assessing them on adaily or weekly basis, the ADerm-SS reduces outcome biases that can arisefrom prolonged recall periods and provides a holistic picture of the impact of thedisease.8

• The ADerm-SS yields three scores (Figure 2): an 11-item total symptom score(ADerm-SS TSS-11) based on all 11 items (0–110), a 7-item total symptom score(ADerm-SS TSS-7) based on 7 items (0–70), and a score specific to skin pain(ADerm-SS Skin Pain; 0–10)7

• Minimal clinically important difference (MCID) thresholds were derived fromclinical trial data as described previously9

REFERENCES1. Kapur S et al. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):43-52.2. Eichenfield LF et al. J Am Acad Dermatol. 2014;71(1):116-32.3. Sidbury R et al. J Am Acad Dermatol. 2014;71:327-49.4. Parmentier JM et al. BMC Rheumatol. 2018;2:1-11.5. Nader A et al. J Clin Pharmacol. 2020;60:528-39.6. Guttman-Yassky E et al. J Allergy Clin Immunol. 2020;145(3):877-84.7. Foley C et al. Curr Med Res Opin. 2019;35(7):1139-48.8. Stull DE et al. Curr Med Res Opin. 2009;25(4):929-42.9. Silverberg JI et al. Revolutionizing Atopic Dermatitis (RAD) Congress. December 13–14,

2020. ePoster

CONCLUSIONS• Once-daily upadacitinib (15 mg or 30 mg) monotherapy significantly

improves patient-reported itch, pain, and other symptoms as assessedby the ADerm-SS through 16 weeks of treatment versus placebo.

• In both upadacitinib treatment groups, there was a difference in responserates as early as Week 1 compared with placebo, and >50% of patientsachieved a response in each ADerm-SS score by Week 4.

• UPA treatment significantly improved patient-reported symptoms acrossall subsets of the ADerm-SS through 16 weeks of treatment.

ACKNOWLEDGMENTSMedical writing services provided by Samantha Francis Stuart of Fishawack Facilitate Ltd, part of Fishawack Health, and funded by AbbVie.

METHODS (CONTINUED)

Figure 2. Atopic Dermatitis Symptom Scale (ADerm-SS) Scoring Paradigm

ADerm-SS items were assessed daily (itch while asleep, itch while awake, and skin pain) or weekly (skin cracking, skin cracking pain, dry skin, skin flaking, rash, skin thickening, bleeding, and oozing). ADerm-SS, Atopic Dermatitis Symptom Scale; MCID, minimal clinically important difference; TSS-7, 7-item total symptom score; TSS-11, 11-item total symptom score.

STATISTICAL ANALYSIS• Data based on the intention-to-treat population were analyzed by nonresponder

imputation while incorporating multiple imputation to handle missing data due toCOVID-19

• P values were calculated according to the Cochran-Mantel-Haenszel testadjusted for main stratification factors (vIGA-AD categories and age [adolescentvs adult]) for the comparison of two UPA groups to placebo

• ADerm-SS results are reported as the proportion of patients achieving a changein score, as compared to baseline, that is greater than or equal to thecorresponding MCID value

RESULTSSTUDY GROUP CHARACTERISTICS• Baseline characteristics were balanced among the three groups within Measure

Up 1 and Measure Up 2, and between each study (Table 1)Table 1. Baseline Patient Demographics

Measure Up 1 Measure Up 2

Characteristic UPA 15 mg n=281

UPA 30 mg n=285

PBO n=281

UPA 15 mg n=276

UPA 30 mg n=282

PBO n=278

Female, N (%) 124 (44.1) 130 (45.6) 137 (48.8) 121 (43.8) 120 (42.6) 124 (44.6)

Age, years, mean (range) 34.1 (12–74) 33.6 (12–75) 34.4 (12–75) 33.3 (12–74) 34.1 (12–75) 33.4 (13–71)

Age group, N (%)

<18 years 42 (14.9) 42 (14.7) 40 (14.2) 33 (12.0) 35 (12.4) 36 (12.9)

≥18 years 239 (85.1) 243 (85.3) 241 (85.8) 243 (88.0) 247 (87.6) 242 (87.1)

EASI, mean (SD) 30.6 (12.8) 29.0 (11.1) 28.8 (12.6) 28.6 (11.7) 29.7 (12.2) 29.1 (12.1)

vIGA-AD, N (%)

Moderate (3) 154 (54.8) 154 (54.0) 156 (55.5) 126 (45.7) 126 (44.7) 125 (45.0)

Severe (4) 127 (45.2) 131 (46.0) 125 (44.5) 150 (54.3) 156 (55.3) 153 (55.0)

Worst Pruritus NRSa, mean (SD) 7.2 (1.6) 7.3 (1.5) 7.3 (1.7) 7.2 (1.6) 7.3 (1.6) 7.3 (1.6)

ADerm-SS TSS-7, mean (SD) 45.7 (14.0) 46.3 (13.4) 46.1 (14.5) 46.8 (13.2) 46.3 (13.8) 47.2 (13.6)

ADerm-SS TSS-11, mean (SD) 68.9 (23.0) 68.9 (21.5) 69.5 (23.2) 70.8 (21.1) 69.8 (22.4) 71.5 (21.9)

ADerm-SS Skin Paina, mean (SD) 6.2 (2.3) 6.5 (2.1) 6.5 (2.4) 6.4 (2.1) 6.4 (2.3) 6.5 (2.2)

Based on ITT Population. Calculations are based on nonmissing records. aWorst Pruritus NRS and ADerm-SS Skin Pain scores are calculated as weekly averages. AD, atopic dermatitis; ADerm-SS, Atopic Dermatitis Symptom Scale; EASI, Eczema Area and Severity Index; ITT, intention to treat; NRS, Numerical Rating Scale; PBO, placebo; SD, standard deviation; TSS-7, 7-item total symptom score; TSS-11, 11-item total symptom score; UPA, upadacitinib; vIGA-AD, validated Investigator’s Global Assessment for AD.

PROPORTION OF PATIENTS REPORTING IMPROVEMENT IN THE ADERM-SS: 7-ITEM TOTAL SYMPTOM SCORE (TSS-7) AFTER 16 WEEKS OF TREATMENT• Clinically meaningful treatment response rates in ADerm-SS TSS-7 were

significantly higher for patients receiving UPA (15 or 30 mg) as compared withplacebo at Week 16 (Figure 3, P<0.001). In both studies, a greater proportion ofpatients achieved a response with UPA as early as Week 1 (nominal P<0.001),and more than 50% of patients receiving UPA achieving a response by Week 4.

RESULTS (CONTINUED)

Figure 3. Proportion of Patients Reporting ≥28-Point Improvement (MCID) in ADerm-SS TSS-7 in Measure Up 1 (A) and Measure Up 2 (B) A. Measure Up 1

Response rate was assessed among subjects with a baseline ADerm-SS TSS-7 score ≥28. MCID for ADerm-SS TSS-7 is 28. ADerm-SS, Atopic Dermatitis Symptom Scale; MCID, minimal clinically important difference; TSS, total symptom score; UPA, upadacitinib. *Nominal P<0.001 for UPA vs placebo. †Multiplicity-controlled endpoint with P<0.001 for UPA vs placebo.

PROPORTION OF PATIENTS REPORTING IMPROVEMENT IN THE ADERM-SS: 11-ITEM TOTAL SYMPTOM SCORE (TSS-11) AFTER 16 WEEKS OF TREATMENT • Patients receiving UPA (15 or 30 mg) had higher clinically meaningful treatment response rates as compared with placebo at Week 16 (Figure 4, nominal P<0.001). In

both studies, a greater proportion of patients achieved a response with UPA as early as Week 1 (nominal P<0.001), and more than 50% of patients receiving UPAachieved a response by Week 4.

Figure 4. Proportion of Patients Reporting ≥44-Point Improvement (MCID) in ADerm-SS TSS-11 in Measure Up 1 (A) and Measure Up 2 (B) A. Measure Up 1

Response rate was assessed among subjects with a baseline ADerm-SS TSS-11 score ≥44. MCID for ADerm-SS TSS-11 is 44. ADerm-SS, Atopic Dermatitis Symptom Scale; MCID, minimal clinically important difference; TSS, total symptom score; UPA, upadacitinib. *Nominal P<0.001 for UPA vs placebo.

PROPORTION OF PATIENTS REPORTING IMPROVEMENT IN THE ADERM-SS: SKIN PAIN ASSESSMENT AFTER 16 WEEKS OF TREATMENT

• The percentage of patients achieving clinically meaningful improvements in skin pain was significantly higher for patients receiving UPA (15 or 30 mg) as compared withplacebo at Week 16 (Figure 5, P<0.001). In both studies, a greater proportion of patients receiving UPA as compared with placebo achieved a response as early as Week1 (nominal P<0.001), and more than 50% of patients receiving UPA achieved a response by Week 4.

Figure 5. Proportion of Patients Reporting ≥4-Point Improvement (MCID) in Skin Pain in Measure Up 1 (A) and Measure Up 2 (B)

A. Measure Up 1

Response rate was assessed among subjects with a baseline ADerm-SS Skin Pain score ≥4. ADerm-SS Skin Pain score is based on a 7-day rolling average. MCID for ADerm-SS Skin Pain score is 4. ADerm-SS, Atopic Dermatitis Symptom Scale; MCID, minimal clinically important difference; UPA, upadacitinib. *Nominal P<0.001 for UPA vs placebo. †Multiplicity-controlled endpoint with P<0.001 for UPA vs placebo.

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