HSC Section 6 Nov2016 Green Book

Fluticasone vs. Esomeprazole for Esophageal Eosinophilia

Proton pump inhibitors (PPIs) are also used to control symptoms associated with EoE and to treat gastroesophageal reflux disease (GERD), the main differential diagnosis of EoE, which can present with similar clinical symptoms and histopathology. According to the AGA consensus statement published in 2007, administra- tion of PPIs to presumed EoE patients was part of the diagnostic evaluation, primarily to exclude GERD as a cause of esophageal eosinophilia (3). If dense eosinophilia persisted following therapy, then a diagnosis of EoE is made. However, some patients with a phenotypic appearance more suggestive of EoE rather than GERD (i.e. young atopic patient presenting with food impaction with concentric rings on endoscopy and having elevated eosinophils on esophageal biopsies) can respond to PPI therapy (4,5). This phe- nomenon now recognized by the more recent and updated EoE consensus statement has been termed PPI-responsive esophageal eosinophilia or PPI-responsive EoE (2,6). The aimof this studywas to performa randomized controlled trial to compare the efficacy of fluticasone propionate (FP) to esomepra- zole (ESO) in patients with esophageal eosinophilia. A secondary aim of this study was to determine whether the presence of GERD impacted the response to therapy in each treatment group. This is a prospective investigator-blinded randomized study. Adult patients (age ≥ 18 years) seen at Walter Reed Army Medical Center (WRAMC) with esophageal eosinophilia were enrolled from April 2008 to October 2010. All patients had at least one clinical symptom of esophageal dysfunction (dysphagia, food impaction, heartburn) with ≥ 15 eosinophils/hpf (eos/hpf; high power field) on index endoscopy. Patients who had a history of secondary hypereosinophilic disorders, severe coagulopathy, or who were pregnant were excluded from the study. Patients who were dilated at index endoscopy were not excluded from the study. Baseline demographic data, history of coexisting atopic diathesis (seasonal allergies, food allergies, asthma, and eczema), and data from index endoscopy (concentric rings, longitudinal furrows, white plaques, mucosal tearing/friability, strictures, Schatzki rings, erosive esophagitis) were collected. All patients completed a validated dysphagia questionnaire, known as the 2-week Mayo Dysphagia Questionnaire (MDQ), following index endoscopy once eosinophilic infiltration was established on biopsies (7). This 29-item instrument is scored from 0 to 100 based on the pres- ence and severity of dysphagia and whether patients avoided or had trouble swallowing different foods (oatmeal, banana, apple, ground meat, bread, and fibrous meat) ( Supplementary file ). Informed consent was obtained from all patients. This study was approved by the WRAMC Institutional Review Board (Work Unit number: 08-14045) and the study was registered at www.clinical- trials.gov (NCT00895817). GERD diagnosis Upon enrollment into the study, all patients underwent 24-h pH with impedance studies. Locationof the lower esophageal sphincter METHODS Study design and patient population

was determined by esophageal manometry utilizing a Solar Sta- tionary GI motility system (Medical Measurement Systems USA, Dover, NH) and an electrically powered water perfusion pump (Mui Scientific, Ontario, CA). A 24-h pH/impedance catheter was then placed 5 cm above the proximal location of the lower esophageal sphincter. The catheter was connected to a ZepHr- reflux recording system (Sandhill Scientific, Highlands Ranch, CO) to capture pH/impedance, as well as symptom data. Subjects returned to our clinic the following day for analysis of the study. Data was analyzed with Bioview Analysis software (Sandhill Sci- entific). GERD was defined by the validated Johnson-DeMeester score (8,9). This scoring method takes into account six param- eters, which include: total % time pH below 4, % time pH below 4 in the upright position, % time pH below 4 in the supine posi- tion, the total number of reflux episodes within a 24-h period, the number of reflux episodes longer than 5min, and the longest reflux episodes in minutes. A composite score is then calculated with a score of greater than 22 being indicative of GERD. The pH drops without accompanying reflux events on impedance and reflux events during meals were excluded from analysis. Randomization and drug administration A computer-generated list of random numbers was used to sepa- rate patients into two equal treatment groups (esomeprazole and fluticasone proprionate). Concealed allocation using a sealed opaque envelope containing data on the sequence of randomi- zation was maintained by a research pharmacist. Following data from the 24-h pH study, patients were stratified into GERD- negative or GERD-positive groups. Within each group, sub- jects were randomized to receive either 40mg of ESO once daily or 440mcg of FP twice daily. Patients randomized to ESO were instructed to take the medicine 30–60min before their first meal. Patients randomized to FP were educated by the research pharma- cist on correct delivery of the medication using an inhaler with- out the use of a spacer and instructed not to drink or eat 30min following administration. The research pharmacist observed the patients priming the metered dose inhaler and administering at least one puff to ensure correct delivery. Adherence was assessed in the ESO arm by counting the number of pills at the end of the treatment study. For the FP arm, the number of puffs was counted using a specially designed metered dose inhaler, which recorded the number of puffs administered. Patients were considered adherent to treatment if ≥ 80% of the medication was taken during the study period. Follow-up Following 8 weeks of treatment, patients underwent repeat upper endoscopy with esophageal biopsies. A total of eight sam- ples using standard biopsy forceps (Boston Scientific, Natick, MA) were taken from all patients, four from the proximal esophagus, ~15 cm from the gastroesophageal junction, and four from the distal esophagus, ~3 cm above the gastroesophageal junction. All endoscopies were performed with Olympus P160 or 180 endoscopes (Olympus, Tokyo, Japan). Endoscopic data was collected including concentric rings, longitudinal furrows,

The American Journal of GASTROENTEROLOGY

© 2013 by the American College of Gastroenterology

120