Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis

Abstract

BackgroundEosinophilic 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 (AT1R) blockade with losartan, an accepted CTD treatment, is a potential EoE treatment. ObjectiveWe 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 multi-site study. MethodsFifteen participants, 5-23 years old, with EoE underwent treatment with a 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 endpoint, while EoE Histology Scoring System (EoEHSS), Endoscopic Reference Scores (EREFS), EoE Diagnostic Panel (EDP), and patient-reported outcomes (PROs) were also assessed. ResultsEsophageal eosinophilia was not reduced following losartan. The peak eosinophil count was not reduced for the proximal (median (IQR): -3 (-22 to 3), p = 0.49) and distal esophagus (median (IQR): -18 (-39 to -1), p = 0.23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, a small subset of 4 participants resolved esophageal eosinophilia with concomitant reduction in EoEHSS and EREFS scores. Across all subjects, the Pediatric EoE Symptom Score and Pediatric Quality of Life Inventory EoE Module and EDP improved following losartan (p < 0.05). ConclusionLosartan treatment associated with improved PRO scores and EDP biomarkers albeit without reducing esophageal eosinophilia overall. A subset of patients demonstrated improved histopathological and endoscopic features which could not be tied to a specific feature which could predict response to treatment.