Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE)

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:78

Article

Simpson, Eric L.¹  Flohr, Carsten^2,3  Eichenfield, Lawrence F.⁴  Bieber, Thomas⁵  Sofen, Howard⁶  Taieb, Alain⁷  Owen, Ryan⁸  Putnam, Wendy⁸  Castro, Marcela⁸  DeBusk, Kendra⁸  Lin, Chin-Yu⁸  Voulgari, Athina⁹  Yen, Karl¹⁰  Omachi, Theodore A.⁸ 

[1] Oregon Hlth & Sci Univ, Sch Med, Dept Dermatol, Portland, OR 97201 USA

[2] Kings Coll London, St Johns Inst Dermatol, London, England

[3] Guys & St Thomas NHS Fdn Trust, London, England

[4] Univ Calif San Diego, Dept Dermatol, La Jolla, CA 92093 USA

[5] Univ Med Ctr, Dept Dermatol & Allergy, Bonn, Germany

[6] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA

[7] Bordeaux Hosp Univ Ctr, Dept Dermatol & Pediat Dermatol, Bordeaux, France

[8] Genentech Inc, 1 DNA Way,MS 452a, San Francisco, CA 94080 USA

[9] Roche Prod Ltd, Global Prod Dev Clin Sci, Welwyn Garden City, Herts, England

[10] Roche, Grenzacherstr, Basel, Switzerland

关键词: anti-IL-13;    atopic dermatitis;    EASI;    lebrikizumab;    pruritus;    topical corticosteroids;   

DOI  :  10.1016/j.jaad.2018.01.017

来源: Elsevier

【 摘 要 】

Background: Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD). Objective: We investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment. Methods: A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1: 1: 1: 1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12. Results: In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P=.026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate. Limitations: Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations. Conclusio Conclusion: When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD.

【 授权许可】

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