TY - JOUR
T1 - Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1)
T2 - a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial
AU - Simpson, Eric L.
AU - Sinclair, Rodney
AU - Forman, Seth
AU - Wollenberg, Andreas
AU - Aschoff, Roland
AU - Cork, Michael
AU - Bieber, Thomas
AU - Thyssen, Jacob P.
AU - Yosipovitch, Gil
AU - Flohr, Carsten
AU - Magnolo, Nina
AU - Maari, Catherine
AU - Feeney, Claire
AU - Biswas, Pinaki
AU - Tatulych, Svitlana
AU - Valdez, Hernan
AU - Rojo, Ricardo
N1 - Funding Information:
ELS is a consultant for Pfizer; reports personal fees from AbbVie, Celgene, Dermira Pharmaceuticals, Galderma, Genentech, Menlo Therapeutics, LEO Pharma, Sanofi Genzyme, Valeant Pharmaceutical, Dermavant, and Pierre Fabre Dermo Cosmetique; grants and personal fees from Anacor Pharma, Eli Lilly, GlaxoSmithKline, Pfizer, Regeneron Pharmaceuticals, and Novartis; and grants from MedImmune, Tioga Pharmaceuticals, and Vanda Pharmaceuticals. RS has been principal investigator in clinical trials, served on advisory boards, received personal fees or non-financial support from Pfizer, AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Coherus, Dermira, Eli Lilly, Galderma, Janssen, LEO Pharma, Principia, MedImmune, Merck, Novartis, Roche, Sanofi-Genzyme, Regeneron, UCB, and Valeant. AW has been an advisor, speaker, or investigator for Pfizer during the conduct of the study; and reports personal fees from AbbVie, Chugai, Galderma, Eli Lilly, MedImmune, Novartis, Pfizer, Regeneron, and Sanofi-Aventis; and grants and personal fees from LEO Pharma, outside the submitted work. RA is a consultant for Pfizer, LEO Pharma, Biofrontera, and Sanofi; and has received speaker fees from Alma Lasers, Biofrontera, Galderma, LEO Pharma, and Sanofi. MC reports grants from Sheffield Teaching Hospitals, during the conduct of the study; grants and personal fees from Sanofi-Genzyme/Regeneron, Pfizer, LEO Pharma, L'Oreal, La Roche-Possay, Johnson & Johnson, Perrigo/ACO Nordic, and Hyphens Pharma; and grants from Galapagos, outside the submitted work. TB reports personal fees from Pfizer, during the conduct of the study; personal fees from Lilly, AbbVie, Sanofi, LEO Pharma, and Galapagos; and grants from Glenmark and Galderma, outside the submitted work. JPT reports personal fees from Pfizer; and is an advisor, investigator, and speaker for Pfizer, AbbVie, Eli Lilly, LEO Pharma, and Sanofi-Genzyme. GY reports grants, personal fees, and non-financial support from Pfizer during the conduct of the study; grants from LEO Pharma and Sun Pharmaceutical Industries; grants and personal fees from Sanofi-Regeneron, Menlo Therapeutics, and Kiniksa; personal fees and non-financial support from Galderma; and personal fees from Sienna Biopharmaceuticals, Trevi Therapeutics, Bellus, Bayer, AbbVie, CeraVe, Novartis, Eli Lilly, and Ortho, outside the submitted work. CFl reports grants from the EU Innovative Medicines Initiative BIOMAP consortium, the UK National Institute for Health Research for TREAT trial, and the British Skin Foundation for UK-Irish Atopic Eczema Systemic Therapy Register, outside the submitted work. CM reports grants from Pfizer, during the conduct of the study; grants and personal fees from Lilly Pharma, Sanofi-Regeneron, and AbbVie; and grants from Asana Bioscience and Glenmark, outside the submitted work. CFe, PB, ST, HV, and RR are employees and shareholders of Pfizer. SF and NM declare no competing interests.
Funding Information:
Editorial and medical writing support under the guidance of authors was provided by Juan Sanchez-Cortes (ApotheCom, San Francisco, CA, USA), and was sponsored by Pfizer.
PY - 2020/7/25
Y1 - 2020/7/25
N2 - Background: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. Methods: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. Findings: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. Interpretation: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. Funding: Pfizer.
AB - Background: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. Methods: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. Findings: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. Interpretation: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. Funding: Pfizer.
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U2 - 10.1016/S0140-6736(20)30732-7
DO - 10.1016/S0140-6736(20)30732-7
M3 - Article
C2 - 32711801
AN - SCOPUS:85088221573
VL - 396
SP - 255
EP - 266
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10246
ER -