Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:78

Article

Guttman-Yassky, Emma^1,2  Brunner, Patrick M.²  Neumann, Avidan U.^3,4,5,6  Khattri, Saakshi¹  Pavel, Ana B.¹  Malik, Kunal¹  Singer, Giselle K.¹  Baum, Danielle¹  Gilleaudeau, Patricia²  Sullivan-Whalen, Mary²  Rose, Sharon¹  On, Shelbi Jim¹  Li, Xuan²  Fuentes-Duculan, Judilyn²  Estrada, Yeriel¹  Garcet, Sandra²  Traidl-Hoffmann, Claudia^3,4,7  Krueger, James G.²  Lebwohl, Mark G.¹ 

[1] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[2] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA

[3] Tech Univ Munich, Univ Ctr Hlth Sci, Inst Environm Med, Klinikum Augsburg, Augsburg, Germany

[4] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Augsburg, Germany

[5] Univ Zurich, Swiss Inst Allergy & Asthma Res, Davos, Switzerland

[6] Charite, Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany

[7] Christine Kuhne Ctr Allergy Res & Educ, Davos, Switzerland

关键词: atopic dermatitis;    fezakinumab;    IL-22;    placebo-controlled trial;    moderate-to-severe AD;   

DOI  :  10.1016/j.jaad.2018.01.016

来源: Elsevier

【 摘 要 】

Background: Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective: Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods: We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results: At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 +/- 2.7 in the fezakinumab arm and 8.0 +/- 3.1 in the placebo arm (P=.134). In the severe AD patient subset (with a baseline SCORAD of >= 50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 +/- 3.8 vs 9.6 +/- 4.2, P=.029) and 20 weeks (27.4 +/- 3.9 vs 11.5 +/- 5.1, P=.010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% +/- 2.4 vs 6.2% +/- 2.7; P=.009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 +/- 0.2 vs 0.3 +/- 0.1; P=.034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations: The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion: Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

【 授权许可】

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