Swiss EoE Clinic and EoE Research Network, Olten, Switzerland.
Allergy. 2013 Mar;68(3):375-85. doi: 10.1111/all.12096. Epub 2013 Feb 5.
Eosinophilic esophagitis (EoE) is a chronic, Th2-type inflammatory disease. Chemoattractant receptor-homologous molecule on Th2 cells (CRTH2) is a prostaglandin D(2) (PGD(2)) receptor, expressed by Th2 cells and other inflammatory cells, including eosinophils and basophils, that mediates chemotaxis and activation. OC000459 is a selective CRTH2 antagonist and would be expected to suppress eosinophilic tissue inflammation. The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE.
In this randomized, double-blind, placebo-controlled trial, 26 adult patients (m/f = 22/4; mean age 41 years, range 22-69 years) with active EoE, dependent or resistant to corticosteroids, were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, and via biomarkers. The primary end point was the reduction in esophageal eosinophil infiltration.
After an 8-week OC000459 treatment, the esophageal eosinophil load decreased significantly, from 114.83 to 73.26 eosinophils per high-power field [(eos/hpf), P = 0.0256], whereas no reduction was observed with placebo (102.80-99.47 eos/hpf, P = 0.870). With OC000459, the physician's global assessment of disease activity improved from 7.13 to 5.18 (P = 0.035). OC000459 likewise reduced extracellular deposits of eosinophil peroxidase and tenascin C, the effects not seen with placebo. No serious adverse events were observed.
An 8-week treatment with the CRTH2-antagonist, OC000459, exerts modest, but significant, anti-eosinophil and beneficial clinical effects in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE and is well tolerated.
嗜酸性食管炎（EoE）是一种慢性、Th2 型炎症性疾病。Chemoattractant receptor-homologous molecule on Th2 cells（CRTH2）是一种前列腺素 D（2）（PGD（2））受体，由 Th2 细胞和其他炎症细胞（包括嗜酸性粒细胞和嗜碱性粒细胞）表达，介导趋化和激活。OC000459 是一种选择性的 CRTH2 拮抗剂，预计可抑制嗜酸性组织炎症。本研究旨在评估 OC000459 单药治疗成人活动性、皮质类固醇依赖或皮质类固醇难治性 EoE 的疗效和安全性。
在这项随机、双盲、安慰剂对照试验中，26 名成年患者（男/女=22/4；平均年龄 41 岁，范围 22-69 岁）患有活动性 EoE，依赖或对皮质类固醇耐药，接受 100mg OC000459（n=14）或安慰剂（n=12）每日两次治疗。治疗前和治疗后评估疾病活动度，包括临床、内镜、组织学和生物标志物。主要终点是食管嗜酸性粒细胞浸润减少。
在 8 周的 OC000459 治疗后，食管嗜酸性粒细胞负荷明显减少，从 114.83 减少到 73.26 个嗜酸性粒细胞/高倍视野（eos/hpf）（P=0.0256），而安慰剂组无减少（102.80-99.47 eos/hpf，P=0.870）。OC000459 还改善了医生对疾病活动度的总体评估，从 7.13 分改善到 5.18 分（P=0.035）。OC000459 还减少了嗜酸性粒细胞过氧化物酶和 tenascin C 的细胞外沉积，而安慰剂则没有观察到这些作用。未观察到严重不良事件。
在患有活动性、皮质类固醇依赖或皮质类固醇难治性 EoE 的成年患者中，8 周的 CRTH2 拮抗剂 OC000459 治疗可产生适度但显著的抗嗜酸性粒细胞和有益的临床效果，且耐受性良好。
