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Reprinted by permission of Am J Gastroenterol. 2013; 108(3):366-372.

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Randomized Controlled Trial Comparing Aerosolized Swallowed Fluticasone to Esomeprazole for Esophageal Eosinophilia

Fouad J. Moawad, MD 1,2 , Ganesh R. Veerappan, MD 1,2 , Johnny A. Dias, DO 1 , Thomas P. Baker, MD 3 , Corinne L. Maydonovitch, BS 1 and Roy K.H. Wong, MD 1,2

OBJECTIVES: Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole. This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gas- troesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440mcg twice daily or esomeprazole 40mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, de- fined as <7eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validat- ed Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment. Forty-two patients (90% male, 81% white, mean age 38±10 years) were randomized into fluticasone ( n =21) and esomeprazole ( n =21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm ( n =4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P =0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group ( P =0.029). In GERD- negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P =1.00). The MDQ score signifi- cantly decreased after treatment with esomeprazole (19±21 vs. 1.4±4.5, P <0.001), but not with fluticasone (17±18 vs. 12±16, P =0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups. CONCLUSIONS: Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD. METHODS: RESULTS:

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg Am J Gastroenterol 2013; 108:366–372; doi:10.1038/ajg.2012.443; published online 12 February 2013

INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic inflammatory immune-mediated condition characterized by symptoms of esophageal dysfunction and the presence of dense eosinophilia

on esophageal biopsies (1). Management, most often with topical steroids, is aimed at improving clinical symptoms and reversing the inflammatory changes within the esophagus to prevent tissue remodeling and formation of fibrosis (2).

1 Department of Medicine, Walter Reed National Military Medical Center, Gastroenterology Service, Bethesda, Maryland, USA; 2 Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; 3 Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA. Correspondence: Fouad J. Moawad, MD, Department of Medicine, Walter Reed National Military Medical Center, Gastroenterology Service, 8901 Rockville Pike, Bethesda, Maryland 20889, USA. E-mail: Fouad.Moawad@us.army.mil Received 16 May 2012; accepted 16 September 2012

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