TY - JOUR
T1 - Efficacy and safety of baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis
T2 - A randomized clinical trial
AU - Reich, Kristian
AU - Kabashima, Kenji
AU - Peris, Ketty
AU - Silverberg, Jonathan I.
AU - Eichenfield, Lawrence F.
AU - Bieber, Thomas
AU - Kaszuba, Aleksandra
AU - Kolodsick, Jill
AU - Yang, Fan E.
AU - Gamalo, Margaret
AU - Brinker, Dennis R.
AU - Delozier, Amy M.
AU - Janes, Jonathan M.
AU - Nunes, Fabio P.
AU - Thyssen, Jacob P.
AU - Simpson, Eric L.
N1 - Funding Information:
Funding/Support: This study was funded by Eli Lilly and Company under license from Incyte Corporation.
Funding Information:
receiving fees to the institution for participation in clinical trials from Eli Lilly and Company during the conduct of the study and personal fees for lectures, advisory board participation, and consulting from AbbVie, Almirall, Kyowa Hakko Kirin, Leo Pharma, Eli Lilly and Company, Pfizer, and Sanofi outside the submitted work. Dr Peris reported receiving personal fees for advisory board participation from AbbVie, Almirall, Eli Lilly and Company, Sanofi, Sun Pharma, Leo Pharma, and Janssen outside the submitted work. Dr Silverberg reported receiving personal fees from Eli Lilly and Company during the conduct of the study and personal fees from Arena, Dermira, Dermavant, Kiniksa, Leo Pharma, MedImmune, Novartis, Galderma, Regeneron-Sanofi, and Pfizer outside the submitted work. Dr Eichenfield reported receiving personal fees for consulting from Eli Lilly and Company during the conduct of the study and receiving grants from AbbVie; receiving grants and personal fees from Pfizer, Dermira, Galderma, Regeneron, and Ortho Dermatology; receiving personal fees from Forte, Novartis, and Sanofi Genzyme; personal fees for data safety monitoring board participation from Asana and Glenmark outside the submitted work. Dr Bieber reported receiving personal fees for lectures and consulting from Eli Lilly and Company during the conduct of the study and personal fees for lectures and consulting from AbbVie, Almirall, AnaptysBio, Arena, Asana, Celgene, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Kymab, Leo Pharma, Novartis, Pfizer, and Sanofi outside the submitted work. Dr Kolodsick reported being an employee and shareholder of Eli Lilly and Company outside the submitted work. Dr Brinker reported being an employee of Eli Lilly and Company. Ms DeLozier reported being an employee and shareholder of Eli Lilly and Company during the conduct of the study and outside the submitted work. Dr Janes reported being an employee and shareholder of Eli Lilly and Company during the conduct of the study and outside the submitted work. Dr Nunes reported being an employee and shareholder of Eli Lilly and Company during the conduct of the study. Dr Thyssen reported receiving personal fees for advising from Eli Lilly and Company during the conduct of the study and personal fees for advising from Pfizer, Regeneron, Sanofi Genzyme, AbbVie, and Leo Pharma outside the submitted work. Dr Simpson reported receiving grants and personal fees from Eli Lilly and Company during the conduct of the study and grants and personal fees from AbbVie, Leo Pharma, Pfizer, and MedImmune; receiving grants from Galderma, Kyowa Hakko Kirin, Merck, Novartis, Tioga, and Celgene; and receiving personal fees from Sanofi Genzyme, Dermira, Boehringe Ingelheim, Dermavant, Forte Bio, Menlo Therapeutics, Incyte, Ortho Dermatologics, Pierre Fabre Dermo Cosmetique, and Valeant outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P =.004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P =.08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.
AB - Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P =.004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P =.08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.
UR - http://www.scopus.com/inward/record.url?scp=85096436715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096436715&partnerID=8YFLogxK
U2 - 10.1001/jamadermatol.2020.3260
DO - 10.1001/jamadermatol.2020.3260
M3 - Article
C2 - 33001140
AN - SCOPUS:85096436715
VL - 156
SP - 1333
EP - 1343
JO - A. M. A. archives of dermatology and syphilology
JF - A. M. A. archives of dermatology and syphilology
SN - 2168-6068
IS - 12
ER -