TY - JOUR
T1 - Efficacy and Safety of Abrocitinib in Combination with Topical Therapy in Adolescents with Moderate-to-Severe Atopic Dermatitis
T2 - The JADE TEEN Randomized Clinical Trial
AU - Eichenfield, Lawrence F.
AU - Flohr, Carsten
AU - Sidbury, Robert
AU - Siegfried, Elaine
AU - Szalai, Zsuzsanna
AU - Galus, Ryszard
AU - Yao, Zhirong
AU - Takahashi, Hidetoshi
AU - Barbarot, Sébastien
AU - Feeney, Claire
AU - Zhang, Fan
AU - Dibonaventura, Marco
AU - Rojo, Ricardo
AU - Valdez, Hernan
AU - Chan, Gary
N1 - Funding Information:
Genzyme, Pfizer/Anacor, and Verrica Equity and personal fees from Almirall, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos, Incyte, LEO Pharma, Novartis, Otsuka, Pfizer/ Anacor, Sanofi Genzyme, Verrica, and Lilly outside the submitted work. Dr Flohr reported grants from the EU BIOMAP consortium, Sanofi, National Institute of Health Research, and British Skin Foundation during the conduct of the study. Dr Sidbury reported nonfinancial support from Regeneron outside the submitted work. Dr Siegfried reported grants from Pfizer and personal fees from Pfizer, Regeneron, Sanofi, and LEO Pharma outside the submitted work. Dr Szalai reported personal fees from Sanofi outside the submitted work. Dr Barbarot reported personal fees from Sanofi Genzyme, LEO Pharma, Lilly, AbbVie, Janssen, Pfizer, UCB Pharma, and Almirall and nonfinancial support from Galderma and Novartis during the conduct of the study. Dr Feeney reported being an employee of Pfizer. Dr Zhang reported being an employee and shareholder of Pfizer during the conduct of the study. Dr DiBonaventura reported personal fees from Pfizer during the conduct of the study. Dr Rojo reported being an employee and shareholder of Pfizer. Dr Valdez reported personal fees and stock options from Pfizer during the conduct of the study and holding a patent for abrocitinib. Dr Chan reported being an employee of Pfizer. No other disclosures were reported.
Funding Information:
designed and funded by Pfizer Inc. Data analyses were conducted by Pfizer Inc. Medical writing and editorial support from ApotheCom (San Francisco, California) were funded by Pfizer Inc.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/10
Y1 - 2021/10
N2 - Importance: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD. Objective: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD. Design, Setting, and Participants: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion. Interventions: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy. Main Outcomes and Measures: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored. Results: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P <.05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P <.05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P <.01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs. Conclusions and Relevance: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT03796676.
AB - Importance: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD. Objective: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD. Design, Setting, and Participants: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion. Interventions: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy. Main Outcomes and Measures: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored. Results: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P <.05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P <.05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P <.01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs. Conclusions and Relevance: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT03796676.
UR - http://www.scopus.com/inward/record.url?scp=85113752830&partnerID=8YFLogxK
U2 - 10.1001/jamadermatol.2021.2830
DO - 10.1001/jamadermatol.2021.2830
M3 - Article
C2 - 34406366
AN - SCOPUS:85113752830
SN - 2168-6068
VL - 157
SP - 1165
EP - 1173
JO - JAMA dermatology
JF - JAMA dermatology
IS - 10
ER -