Efficacy of the oral chemoattractant receptor homologous molecule on T_H2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis

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• 作者：Norbert Krug ; Abhya Gupta ; Philipp Badorrek ; Ruediger Koenen ; Meike Mueller ; Anna Pivovarova ; James Hilbert ; Kristiane Wetzel ; Jens M. Hohlfeld ; Chester Wood
• 关键词：Chemoattractant receptor homologous molecule on TH2 cells ; BI 671800 ; environmental challenge chamber ; prostaglandin D2 ; seasonal allergic rhinitis ; inflammation
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：February, 2014
• 年：2014
• 卷：133
• 期：2
• 页码：414-419.e8
• 全文大小：1318 K

文摘

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Background

The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D₂ receptor chemoattractant receptor homologous molecule on T_H2 cells (CRTH2).

Objective

We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 渭g once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR.

Methods

In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours. The primary efficacy variable was the total nasal symptom score assessed as the area under the curve (AUC)_0-6h.

Results

In total, 146 patients (63.7% male; mean age, 36.1聽years) were randomized. The adjusted mean total nasal symptom score AUC_0-6h was significantly reduced versus placebo with 200 mg of BI 671800 (absolute difference, 鈭?.85; percentage difference, 鈭?7%; P聽= .0026), montelukast (absolute difference, 鈭?.74; percentage difference, 鈭?5%; P聽= .0115), and fluticasone propionate (absolute difference, 鈭?.64; percentage difference, 鈭?3%; P聽< .0001). Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P聽< .05 for all doses), significantly inhibited nasal inflammatory cytokine levels (IL-4 and eotaxin, P聽< .05; 200 mg twice daily), and induced a dose-related reduction in ex聽vivo prostaglandin D₂-mediated eosinophil shape change.

Conclusion

Two hundred milligrams of BI 671800 twice daily聽demonstrated efficacy in treating SAR symptoms induced by environmental challenge chamber allergen exposure and had a favorable safety profile.