Oral Viscous Budesonide is Effective in Children with Eosinophilic Esophagitis in a Randomized, Plac

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Oral Viscous Budesonide is Effective in Children with Eosinophilic Esophagitis in a Randomized, Placebo-controlled Trial

Abstract and Introduction

Abstract


Background & Aims: Eosinophilic esophagitis (EoE) is caused by immunologic reactions to ingested/inhaled allergens. The diagnosis is considered if ≥15 eosinophils per high-powered field (eos/hpf) are detected in mucosal biopsies. Placebo-controlled studies have not been conducted to evaluate the safety and efficacy of oral viscous budesonide (OVB).
Methods: Children with EoE were randomly assigned to groups that were given OVB (n = 15) or placebo (n = 9). Patients <5 feet and ≥5 feet tall received 1 mg and 2 mg OVB daily, respectively. All patients received lansoprazole. Duration of treatment was 3 months, followed by repeat endoscopy and biopsies. Patients were classified as responders if their peak eosinophil counts were ≤6 eos/hpf, partial responders were 7–19 eos/hpf, and nonresponders were ≥20 eos/hpf. Baseline and post-treatment symptoms and endoscopic and histologic features were scored.
Results: Thirteen (86.7%) children given OVB (P < .0001) and none who received placebo (P = .3) were classified as responders. Mean pre-/post-treatment peak eosinophil counts were 66.7 and 4.8 eos/hpf, respectively, in the group given OVB (P < .0001); they were 83.9 and 65.6 eos/hpf, respectively, in the group given placebo (P = .3). In the group given OVB, there were significant reductions from baseline values in proximal (P = .002), mid (P = .0003), and distal (P = .001) esophageal eosinophilia. After OVB therapy, compared with baseline, the mean symptom (P = .0007), endoscopy (P = .0005), and histology scores improved (P = .0035) significantly.
Conclusions: OVB is an effective treatment of pan-esophageal disease in children with EoE. OVB improves symptoms and endoscopic and histologic features. Proton pump inhibitor single therapy did not significantly improve esophageal eosinophilia or symptoms of EoE.

Introduction


Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by esophageal eosinophilia and gastrointestinal symptoms. It most likely represents an immunologic reaction to ingested and inhaled allergens. Prevalence of EoE is increasing with rates now ranging from 6 to 30 cases per 100,000. Although this may also represent increased physician-recognition, it is likely that the rise in prevalence is real and mirrors the recent increase in prevalence of atopic disorders, such as asthma. The diagnosis of EoE is dependent upon finding ≥15 eosinophils per high power field (eos/hpf) in esophageal mucosal biopsies. Symptoms of EoE often mimic gastroesophageal reflux disease (GERD), but are often refractory to acidsuppression therapy. Symptoms include regurgitation, vomiting, pain, anorexia, and dysphagia. Although the optimal therapy for EoE is unclear, a major concern for untreated EoE is esophageal remodeling and development of strictures, which are reported in 16%–40% of adult patients. A likely prerequisite of esophageal remodeling is the presence of lamina propria (LP) fibrosis, as seen under light microscopy and measured by levels of transforming growth factor–β1 (TGFβ1) and phosphorylated Smad2/3. We recently reported that LP remodeling associated with EoE diminishes with topical corticosteroid therapy, and that patients with specific polymorphisms in the TGFβ1-promotor gene may respond better to corticosteroid therapy.

Treatment options for EoE are dietary restriction including those identified by skin testing, 6-food elimination diet, and elemental formula. Systemic corticosteroids are effective but are seldom warranted. Topical corticosteroids, such as fluticasone proprionate, administered through a metered-dose inhaler, and oral viscous budesonide suspension (OVB), can safely induce and maintain low esophageal eosinophil levels. We previously reported our retrospective experience of 20 children with EoE treated with OVB for 3–4 months. Eighty percent of these patients achieved the histologic study end point and also had significant improvement of their symptoms and endoscopic findings.

In this report, we describe the results of the first placebo-controlled study using OVB for the treatment of EoE in children. Histologic, symptomatic, and endoscopic responses to OVB therapy are reported. In addition, esophageal biopsies containing LP were evaluated for vascular activation and TGFβ1.

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