Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md.
J Allergy Clin Immunol Pract. 2024 Sep;12(9):2427-2438.e3. doi: 10.1016/j.jaip.2024.07.011. Epub 2024 Jul 25.
Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE. Therefore, angiotensin II type 1 receptor blockade with losartan, an accepted CTD treatment, is a potential EoE treatment.
We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multisite study.
Fifteen participants with EoE, aged 5 to 23 years, underwent treatment with per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard of care therapy and 14 patients completed the study. Eosinophil counts served as the primary end point, whereas we also assessed the EoE Histology Scoring System, Endoscopic Reference Scores, EoE Diagnostic Panel, and patient-reported outcomes.
Esophageal eosinophilia was not reduced after losartan. The peak eosinophil count was not reduced for the proximal (median [interquartile range]: -3 [-22 to 3]; P = .49) and distal esophagus (median [interquartile range]: -18 [-39 to -1]; P = .23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, in a small subset of four participants esophageal eosinophilia was resolved with a concomitant reduction in EoE Histology Scoring System score and Endoscopic Reference Score. Across all subjects, the Pediatric EoE Symptom Score, Pediatric Quality of Life Inventory EoE Module, and EoE Diagnostic Panel improved after losartan (P < .05).
Losartan treatment was associated with improved patient-reported outcome scores and EoE Diagnostic Panel biomarkers although without a reduction in esophageal eosinophilia overall. A subset of patients demonstrated improved histopathologic and endoscopic features that could not be tied to a specific feature predicting response to treatment.
嗜酸性食管炎(EoE)是一种慢性、食物抗原驱动的食管疾病。结缔组织疾病(CTDs)和食管结缔组织改变与 EoE 相关。因此,血管紧张素 II 型 1 型受体阻滞剂氯沙坦(一种公认的 CTD 治疗药物)是潜在的 EoE 治疗药物。
我们在一项开放标签、非安慰剂对照的多中心研究中,评估了氯沙坦对患有和不患有 CTD 的 EoE 患者的食管病理学、症状和安全性的影响。
15 名年龄在 5 至 23 岁的 EoE 患者接受了按方案滴定剂量的氯沙坦治疗,为期 16 周的开放标签先导试验。氯沙坦被添加到标准治疗中,14 名患者完成了研究。嗜酸性粒细胞计数是主要终点,我们还评估了 EoE 组织学评分系统、内镜参考评分、EoE 诊断小组和患者报告的结果。
氯沙坦治疗后食管嗜酸性粒细胞没有减少。近端食管(中位数[四分位距]:-3[-22 至 3];P=.49)和远端食管(中位数[四分位距]:-18[-39 至-1];P=.23)的嗜酸性粒细胞计数峰值没有减少。EoE 伴或不伴 CTD 的患者(分别为 n=7 和 n=8)的氯沙坦反应无差异。尽管如此,在一小部分 4 名参与者中,食管嗜酸性粒细胞减少与 EoE 组织学评分系统评分和内镜参考评分降低同时发生。在所有受试者中,儿科 EoE 症状评分、儿科生活质量量表 EoE 模块和 EoE 诊断小组在使用氯沙坦后均得到改善(P <.05)。
尽管总体上食管嗜酸性粒细胞没有减少,但氯沙坦治疗与患者报告的结局评分和 EoE 诊断小组的生物标志物改善相关。一小部分患者表现出改善的组织病理学和内镜特征,这些特征不能与治疗反应的特定预测特征联系起来。