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Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.
JAMA Dermatol. 2020 12 01; 156(12):1333-1343.JD

Abstract

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.

Authors+Show Affiliations

Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Skin flammation Center, Hamburg, Germany.Department of Dermatology, Kyoto University, Kyoto, Japan. Skin Research Institute of Singapore and Singapore Immunology Network, A*Star, Singapore.Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS- Università Cattolica del Sacro Cuore, Rome, Italy.Department of Dermatology, George Washington University School of Medicine, Washington, DC.Department of Dermatology, University of California, San Diego and Rady Children's Hospital, San Diego, California. Department of Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, California.Department of Dermatology and Allergy, University Hospital of Bonn, Bonn, Germany.Dermed Centrum Medyczne, Lodz, Poland.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Eli Lilly and Company, Indianapolis, Indiana.Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Hellerup, Denmark.Department of Dermatology, Oregon Health and Science University, Portland.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33001140

Citation

Reich, Kristian, et al. "Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: a Randomized Clinical Trial." JAMA Dermatology, vol. 156, no. 12, 2020, pp. 1333-1343.
Reich K, Kabashima K, Peris K, et al. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020;156(12):1333-1343.
Reich, K., Kabashima, K., Peris, K., Silverberg, J. I., Eichenfield, L. F., Bieber, T., Kaszuba, A., Kolodsick, J., Yang, F. E., Gamalo, M., Brinker, D. R., DeLozier, A. M., Janes, J. M., Nunes, F. P., Thyssen, J. P., & Simpson, E. L. (2020). Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatology, 156(12), 1333-1343. https://doi.org/10.1001/jamadermatol.2020.3260
Reich K, et al. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: a Randomized Clinical Trial. JAMA Dermatol. 2020 12 1;156(12):1333-1343. PubMed PMID: 33001140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: 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, PY - 2020/10/2/pubmed PY - 2021/3/19/medline PY - 2020/10/1/entrez SP - 1333 EP - 1343 JF - JAMA dermatology JO - JAMA Dermatol VL - 156 IS - 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. SN - 2168-6084 UR - https://www.unboundmedicine.com/medline/citation/33001140/Efficacy_and_Safety_of_Baricitinib_Combined_With_Topical_Corticosteroids_for_Treatment_of_Moderate_to_Severe_Atopic_Dermatitis:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jamadermatology/fullarticle/10.1001/jamadermatol.2020.3260 DB - PRIME DP - Unbound Medicine ER -