Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis: Analysis of Follow-up Data From the Measure Up 1 and Measure Up 2 Randomized Clinical Trials

Abstract

Importance: Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.

Objective: To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis.

Design, setting, and participants: Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2).

Interventions: Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner.

Main outcomes and measures: Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed.

Results: Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals.

Conclusions and relevance: In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.

Trial registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).

Conflict of interest statement

Conflicts of Interest Disclosures: Dr Simpson reported receiving grants from AbbVie, Amgen, Arcutis, Corevita, Dermira, Eli Lilly, Incyte, Kyowa Hakko Kirin, Leo Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and TARGET-DERM and personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Boston Consulting Group, Collective Acumen, Dermira, Eli Lilly, Evidera, Excerpta Medica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Pfizer, Physicians World LLC, Regeneron, Sanofi Genzyme, Trevi Therapeutics, and WebMD outside the submitted work. Dr Papp reported receiving grants, personal fees, and nonfinancial support from AbbVie during the conduct of the study; and receiving grants from Amgen, Boehringer Ingelheim, Dermira, Janssen, Kyowa Kirin, Leo Pharma, Novartis, Pfizer, Incyte, Arcutis, Akros, Anacor, Avillion, Bausch Health, Baxalta, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Gilead, Merck, Regeneron, and Sun Pharma and personal fees from Can-Fite, Dice Pharmaceuticals, Evelo, Meiji Seika Pharma, Mitsubishi Tanabe, Sanofi Genzyme, and Takeda outside the submitted work. Dr Blauvelt reported receiving personal fees from AbbVie as a scientific consultant and other from AbbVie (company has received funds to perform clinical trial work) during the conduct of the study; and having served as a scientific adviser for (received honoraria from) Abcentra, Aligos Therapeutics, Almirall, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo, Novartis, Pfizer, RAPT, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, and Vibliome Therapeutics, and having acted as a clinical study investigator for (institution has received clinical study funds from) Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma outside the submitted work. Dr C. Chu reported receiving personal fees from AbbVie (investigator, speaker fee, and consultant fee) during the conduct of the study; and serving as an investigator for AbbVie, Dermira, Lilly, Novartis, Oneness Biotech, Pfizer, Regeneron, Roche, Sanofi, and United BioPharma; receiving personal fees from AbbVie, Janssen, Lilly, Mylan, Novartis, Pfizer, Roche, Sanofi, United BioPharma, and Viatris; and receiving grants from Novartis, Regeneron, and Sanofi outside the submitted work. Dr Hong reported receiving grants, fees, and nonfinancial support from AbbVie, Pfizer, Leo, and Sanofi Genzyme and receiving grants from Incyte, Dermavant, and Eli Lilly outside the submitted work. Dr Katoh reported receiving grants and personal fees from AbbVie during the conduct of the study; and receiving grants from Maruho, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Sanofi, Kyowa Kirin, Sun Pharma, Taiho Pharmaceutical, and Leo Pharma, and personal fees from Sanofi, Maruho, Eli Lilly Japan, Taiho Pharmaceutical, Jansen Pharma, Mitsubishi Tanabe Pharma, Kyowa Kirin, Celgene Japan, and Leo Pharma outside the submitted work. Dr Thyssen reported receiving personal fees from AbbVie for speaking and advising during the conduct of the study; and receiving grants from Regeneron, Sanofi Genzyme, and Pfizer and personal fees from Leo Pharma, Lilly, OM-85, Almirall, Asana, and Arena outside the submitted work. Dr Chiou reported other from AbbVie (clinical study investigator and consultant) during the conduct of the study; serving as a clinical study investigator for Sanofi, Dermira, Eli Lilly, and Regeneron; personal fees for medical advisory boards from Pfizer and Trevi Therapeutics outside the submitted work. Dr Bissonnette reported consulting for AbbVie, EMD Serono, Evidera, BlueFin, Kyowa Kirin, and Inmagene Bio; receiving grants and other (consultation and advisory board) from Arena, Eli Lilly, Sanofi Genzyme, Incyte, and LEO Pharma; receiving grants and other (advisory board) from Arcutis and Dermavant; receiving grants and other (consultation) from Boehringer Ingelheim, Cara Therapeutics, and Target RWE; serving on advisory boards for Galderma and GlaxoSmithKline; being a shareholder of Innovaderm; receiving grants from Bellus, Kiniksa Pharmaceuticals, Novan, Pfizer, Relaxer Therapeutics, Regeneron, and Vyne Therapeutics; and receiving grants and other from RAPT Therapeutics outside the submitted work. Dr Stein Gold reported receiving grants and personal fees from AbbVie, Pfizer, Incyte, Arcutis, and Dermavant; grants from Lilly; and personal fees from Regeneron and Sanofi during the conduct of the study. Dr Hu reported receiving personal fees from AbbVie (salary) outside the submitted work. Dr J. Liu reported being an employee of AbbVie Inc and receiving payment and holding stocks. Dr Tenorio reported being an employee of AbbVie. Dr A. Chu reported receiving personal fees from AbbVie (employment and stock options) during the conduct of the study and outside the submitted work. Dr Guttman-Yassky reported receiving grants from AbbVie during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Efficacy Over Time for EASI 75, vIGA-AD 0/1, and Worst Pruritus NRSa Improvement of 4 or Greater Through Week 52 (ITT Population and Integratedb Data, OC Analysis)

Response rates at each visit for EASI 75 (A), vIGA-AD 0/1 (B), and worst pruritus NRSa improvement of 4 or greater (C) in the Measure Up 1 trial, the Measure Up 2 trial, and the integratedb data set. aBased on weekly average (through week 16); based on study visit (weeks 20 through 52) for patients with worst pruritus NRS of 4 or greater at baseline. bData from Measure Up 1 and Measure Up 2 studies. EASI 75 indicates 75% or greater improvement in Eczema Area and Severity Index; ITT, intention to treat for the main study; NRS, numeric rating scale; OC, observed case; PBO, placebo; UPA, upadacitinib; vIGA-AD 0/1, Validated Investigator Global Assessment for Atopic Dermatitis of clear (0) or almost clear (1) with 2 or more grades of reduction.

Figure 2.. Efficacy Over Time for EASI 90, EASI 100, vIGA-AD 0 With a Reduction From Baseline of 2 or Greater, and Worst Pruritus NRS 0/1a Through Week 52 (ITT Population and Integratedb Data, OC Analysis)

aFor patients with worst pruritus NRS greater than 1 at baseline. bData from Measure Up 1 and Measure Up 2 studies. EASI 90/100 indicates 90% or greater/100% improvement in Eczema Area and Severity Index; ITT, intention to treat for the main study; NRS, numeric rating scale; OC, observed case; PBO, placebo; UPA, upadacitinib; vIGA-AD 0, Validated Investigator Global Assessment for Atopic Dermatitis of clear with 2 or greater grades of reduction.