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      Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis: a review of the latest evidence

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          Abstract

          Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. The incidence of EoE has increased substantially over the past two decades in Europe and North America. The natural course of EoE appears to be progressive with a high risk of stricture formation. The current European guideline recommend swallowed topical corticosteroids, proton-pump inhibitors or dietary intervention for initial and long-term treatment of EoE. Swallowed topical corticosteroids can be considered to be the best studied drug class in EoE, with more than 1000 patients enrolled in randomized clinical trials worldwide. In most of them, fluticasone or budesonide formulations have been used that were originally designed for asthma therapy, thus presumably suboptimal for EoE treatment. The new orodispersible budesonide tablet with effervescent properties is the first approved esophageal-targeted formulation specifically developed for the treatment of EoE, which has become available in many European countries. This article gives an overview of the evolution of topical corticosteroids in EoE and provides an update on recent data from large-scale multicenter trials exploring the efficacy and safety of the orodispersible budesonide tablet with effervescent properties in adult EoE patients.

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          Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.

          Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation.
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            Epidemiology and Natural History of Eosinophilic Esophagitis

            Eosinophilic esophagitis (EoE) has emerged over the past 2 decades as a major cause of upper gastrointestinal morbidity. Over this time, the epidemiology of EoE has also rapidly evolved. EoE has transformed from a rare case-reportable condition to disease that is commonly encountered in the gastroenterology clinic, hospital emergency room, and endoscopy suite. The incidence and prevalence are increasing at rates that outpace increased disease recognition. Current incidence estimates range from 5 to 10 cases per 100,000, and current prevalence estimates range from 0.5 to 1 case per 1000. We review the data and potential reasons behind this increase, examine risk factors, and identify important areas for research into disease etiology. The article also discusses the progression of EoE from an inflammatory to fibrostenotic phenotype. An accurate view of the natural history of EoE is central to discussions with patients regarding disease prognosis and decisions about long-term use of medical, endoscopic, and diet therapies. Progressive remodelling appears to be gradual, but not universal, and the duration of untreated disease is the best predictor of stricture risk. Ultimately, prospective, long-term outcome studies focusing on multiple aspects of disease activity are needed to fully understand the natural history of EoE.
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              Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis.

              Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy. EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effect of oral budesonide (1 mg twice daily for 15 days) in adolescent and adult patients with active EoE. Pretreatment and posttreatment disease activity was assessed clinically, endoscopically, and histologically. The primary end point was reduced mean numbers of eosinophils in the esophageal epithelium (number per high-power field [hpf] = esophageal eosinophil load). Esophageal biopsy and blood samples were analyzed using immunofluorescence and immunoassays, respectively, for biomarkers of inflammation and treatment response. A 15-day course of therapy significantly decreased the number of eosinophils in the esophageal epithelium in patients given budesonide (from 68.2 to 5.5 eosinophils/hpf; P < .0001) but not in the placebo group (from 62.3 to 56.5 eosinophils/hpf; P = .48). Dysphagia scores significantly improved among patients given budesonide compared with those given placebo (5.61 vs 2.22; P < .0001). White exudates and red furrows were reversed in patients given budesonide, based on endoscopy examination. Budesonide, but not placebo, also reduced apoptosis of epithelial cells and molecular remodeling events in the esophagus; no serious adverse events were observed. A 15-day course of treatment with budesonide is well tolerated and highly effective in inducing a histologic and clinical remission in adolescent and adult patients with active EoE. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Therap Adv Gastroenterol
                Therap Adv Gastroenterol
                TAG
                sptag
                Therapeutic Advances in Gastroenterology
                SAGE Publications (Sage UK: London, England )
                1756-283X
                1756-2848
                10 June 2020
                2020
                : 13
                : 1756284820927282
                Affiliations
                [1-1756284820927282]Center for Digestive Diseases, Internal Medicine Center Eppendorf, and Center for Esophageal Disorders, University Hospital Eppendorf, Eppendorfer Landstraße 42, Hamburg, 20249, Germany Center for Esophageal Disorders, University Hospital Eppendorf, Hamburg, Germany
                [2-1756284820927282]Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Castilla-La Mancha, Spain
                [3-1756284820927282]Department of Gastroenterology, Swiss EoE Clinics, University Hospital Zurich, Zurich, Switzerland
                [4-1756284820927282]Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, North Holland, The Netherlands
                [5-1756284820927282]Department of Health Services Research, Durham University, Durham, UK
                Author notes
                Author information
                https://orcid.org/0000-0002-9297-3349
                Article
                10.1177_1756284820927282
                10.1177/1756284820927282
                7288799
                32565912
                5147cf4a-4389-43ab-9f42-2c6cd535b38b
                © The Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 28 November 2019
                : 15 April 2020
                Categories
                Review
                Custom metadata
                January-December 2020

                budesonide,eosinophilic esophagitis,review,topical corticosteroids

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