Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials

Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis. Measure Up 1 and Measure U...

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Published in:The Lancet (British edition) 2021-06, Vol.397 (10290), p.2151-2168
Main Authors: Guttman-Yassky, Emma, Teixeira, Henrique D, Simpson, Eric L, Papp, Kim A, Pangan, Aileen L, Blauvelt, Andrew, Thaçi, Diamant, Chu, Chia-Yu, Hong, H Chih-ho, Katoh, Norito, Paller, Amy S, Calimlim, Brian, Gu, Yihua, Hu, Xiaofei, Liu, Meng, Yang, Yang, Liu, John, Tenorio, Allan R, Chu, Alvina D, Irvine, Alan D
Format: Article
Language:English
Subjects:
Acne
Adolescent
Adolescents
Adult
Adults
Adverse events
Aged
Asthma
Atopic dermatitis
c-Met protein
Clinical trials
COVID-19
Creatine
Creatine kinase
Cytokines
Dermatitis
Dermatitis, Atopic - drug therapy
Diabetes
Dosage
Dose-Response Relationship, Drug
Double-Blind Method
Double-blind studies
Eczema
Elevation
Enzyme inhibitors
Female
Health services
Heterocyclic Compounds, 3-Ring - administration & dosage
Heterocyclic Compounds, 3-Ring - therapeutic use
Humans
Inflammatory bowel disease
Interactive systems
Janus kinase
Janus Kinase 1
Janus kinase 2
Janus Kinase Inhibitors - administration & dosage
Janus Kinase Inhibitors - therapeutic use
Kinases
Male
Middle Aged
Pathogenesis
Patients
Placebos
Protein-tyrosine kinase
Pruritus
Quality of life
Respiratory tract
Respiratory tract diseases
Rheumatoid arthritis
Rhinopharyngitis
Risk assessment
Safety
Severity of Illness Index
Skin
Skin diseases
Teenagers
Tyrosine
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Summary:Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis. Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12–17 years) and adults (aged 18–75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis [vIGA-AD] score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting. Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(21)00588-2