Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Review

Werfel, Thomas¹  Layton, Gary²  Yeadon, Michael³  Whitlock, Lyndsey³  Osterloh, Ian⁴  Jimenez, Pablo³  Liu, Wai³  Lynch, Victoria⁵  Asher, Aliya⁶  Tsianakas, Athanasios⁷  Purkins, Lynn³ 

[1] Hannover Med Sch, Klin Dermatol Allergol & Venerol, Hannover, Germany

[2] ParamStat, Ash, England

[3] Ziarco Pharma, Discovery Pk, Sandwich, Kent, England

[4] Ostermed, Birmingham Business Pk, Birmingham, W Midlands, England

[5] MAC Clin Res, Leeds, W Yorkshire, England

[6] MAC Clin Res, Manchester, Lancs, England

[7] Univ Hosp Muenster, Dept Dermatol, Munster, Germany

关键词: Atopic dermatitis;    atopic eczema;    eczema;    histamine 4 receptor antagonist;    Eczema Area and Severity Index;    SCORAD;    Investigator's Global Assessment;    pruritus;   

DOI  :  10.1016/j.jaci.2018.07.047

来源: Elsevier

【 摘 要 】

Background: H-4 receptor antagonists are potential novel treatments for inflammatory skin diseases, including atopic dermatitis (AD). Objective: We sought to study the efficacy and safety of ZPL-3893787 (a selective H-4 receptor antagonist) in patients with moderate-to-severe AD. Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30 mg) once-daily oral therapy in adults with moderate-tosevere AD. Patients were randomized (2:1) to ZPL-3893787 (n = 65) or placebo (n = 33) for 8 weeks. Patients had a history of AD for more than 12 months, Eczema Area and Severity Index (EASI) scores of 12 or greater and 48 or less, Investigator's Global Assessment (IGA) scores of 3 or greater, pruritus scores of = or greater (0- to 10-point scale), and AD on 10% or greater of body surface area. Efficacy parameters included EASI, IGA, SCORAD, and pruritus assessment. Results: Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared with 27% for placebo. The placebo-adjusted reduction in EASI score at week 8 was 5.1 (1-sided P = .01). Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 versus 9.1% with placebo. SCORAD scores exhibited 41% reduction with ZPL-3893787 versus 26% with placebo (placebo-adjusted reduction of 10.0, P = .004). There was a 3-point reduction (scale, 1-10) in pruritus with ZPL-3893787, but there was a similar reduction with placebo, resulting in a nonsignificant difference (P 5.249). Patient-reported pruritus subscores obtained from SCORAD were reduced with ZPL-3893787 compared with placebo at week 8 (nonsignificant). ZPL-3893787 was well tolerated. Conclusion: For the first time, these results showed that ZPL-3893787 improved inflammatory skin lesions in patients with AD, confirming H-4 receptor antagonism as a novel therapeutic option.

【 授权许可】

Free