Esomeprazole 20 mg provides more effective acid control than lansoprazole 15 mg

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Abstracts

AJG – Vol. 96, No. 9, Suppl., 2001

134 Prospective, randomized Barrett’s ablation: MPEC vs APC: efficacy, adverse events, and long-term follow-up Allan P Weston1*, Daniela Mitreva1 and Prateek Sharma1. 1GI, VAMC, Kansas City, MO, United States; and 2Medicine, Univ Kansas Medical Center, Kansas City, KS, United States. Purpose: Thermal ablation of Barrett’s esophagus (BE) by either MPEC or APC has been reported with variable results. No studies have compared the two techniques nor has long-term follow up data been published. We report the early results of a prospective, randomized, non-blinded BE ablation protocol comparing the effectiveness, adverse event profile, and long-term endoscopic and histologic outcome post-ablation. Methods: BE patients with no dysplasia or only LGD were asked to participate. All patients received PPI throughout ablation as well as postablation. Ablation performed at 8 week intervals with ERBE unit all visible columnar epithelium was destroyed above the GEJ. Once BE was fully ablated, jumbo surveillance biopsies were taken at 1 to 2 cm intervals of neosquamous epithelium at 6 to 12 month intervals for evaluation of underlying columnar epithelium. Scrunity of SCJ for evidence of regrowth of columnar epithelium post-ablation was also done, with biopies taken of any tongue or island above GEJ. Adverse events investigated by scheduled telephone interviews. Fishers chi-square performed for statisical analyses. Results: A total of 20 patients have entered study and have been followed for more than 6 months post-complete ablation. All 20 were males, mean age of 51.9 yrs with BE length ranging from 1 to 10 cm (mean 4.2 cm). 7/20 BE had prior fundoplications and 9/20 had BE with LGD. Incidence of adverse events is shown in the table below. During long-term follow up, ranging 6 to 27 months post complete BE ablation, 2 patients had regrowth of small tongues of Barrett’s epithelium (0.5 cm up to 1.5 cm in length) noted at 19 months post ablation visit. A single minute focus of underlying columnar epithelium has also been noted on surveillance biopsies of neo-squamous epithelium in 2 patients (one of whom also had BE regrowth). Conclusions: Both APC and MPEC are equally effective at ablating BE. The incidence of side effects from thermal ablation is greater for APC than MPEC, but not significant. Disturbing is the 10% incidence of BE regrowth during long-term follow up, despite PPI, as well as 10% incidence of buried columnar epithelium.

Chest pain Odynophagia Dysphagia Stricture Bleeding Perforation

APC

MPEC

p value

4/9 44% 6/9 (67%) 2/9 (22%) 1/9 (11%) 0/9 (0%) 0/9 (0%)

4/11 (36%) 7/11 (64%) 1/9 (9%) 0/11 (0%) 0/11 (0%) 0/11 (0%)

ns ns ns ns ns ns

135 Risk stratification of Barrett’s esophagus: updated prospective multivariate analysis Allan P Weston1*, Ruth Hassanien2 and Prateek Sharma1. 1GI, VAMC, Kansas City, MO, United States; and 2Medicine, Univ Kansas Medical Center, Kansas City, KS, United States. Purpose: Barrett’s esophagus(BE) is a premalignant disease necessitating periodic endoscopic surveillance to survey for progression to either highgrade dysplasia (HGD) or adenocarcinoma (Ca). Cost effective BE surveillance strategies demand establishment of markers to predict progression of BE (i.e risk stratification). We previously reported several features predictive of progression of BE (Am J Gastroenterol 1999;94:3413–19). Herein we provide an update on the prospective evaluation of factors predictive of progression to either multifocal HGD (mHGD), HGD within dysplasia associated lesion or mass (DALM), or Ca.

Methods: All BE patients who met the following criteria are included in the analysis: 1) Seattle BE bx protocol within 3 months of index dx, b) surveillance examinations at intervals meeting or exceeding ACG guidelines with Seattle bx protocol, and c) minimum follow up of 1 year. Exclusion criteria: mHGD or Ca at index dx, or unable to undergo surveillance. Factors examined by multivariate analysis (stepwise logistic regression and Cox proportional hazards) included: patient age, race (white:other), length of BE in cm, hiatal hernia (no:yes), histology at index dx (no dys, LGD, uHGD), histology during f/u (no dys, LGD, uHGD), and H.pylori status. LGD and HGD dx required confirmation. Results: 201 patients, mean age ⫾ SD of 61.3 ⫾ 12.3 have met all inclusion criteria. Length of BE was ⬍3 cm in 104 (mean of 3.7 cm). At initial dx, 156 had no dysplasia, 35 (17.4%) had LGD, and 10 (5%) HGD. To date 19 (9.5%) have developed mHGD/HGD-DALM/Ca. Duration of follow up ranges from 12 to 129 mos (mean ⫾ SD of 46.5 ⫾ 26.0). Stepwise logistic regression showed a significant and independent association of presence of dysplasia anytime during f/u (p ⬍ 0.0001) and length of BE ⱖ6 cm (p ⫽ 0.0006). Cox proportional hazards gave similar results: presence of dysplasia anytime during follow up (p ⬍ 0.0001) and BE length (p ⫽ 0.0331). Table of predictive probability of BE progression shown below. Conclusions: Simple, easily attainable endoscopic and histologic features of BE are predictive of risk of progression and can be used to determine surveillance intervals and candidates for chemoprevention trials. Histology at Index Dx no dysplasia no dysplasia LGD LGD uHGD uHGD

BE length ⬍6 ⱖ6 ⬍6 ⱖ6 ⬍6 ⱖ6

cm cm cm cm cm cm

probability 0.2% 1.9% 5.1% 32.6% 57.6% 92.4%

136 Esomeprazole 20 mg provides more effective acid control than lansoprazole 15 mg Clive H Wilder-Smith MD1*, Kerstin Ro¨ hss PhD2 and Catharina ClaarNilsson RN2. 1Gastrointestinal Unit & GI Physiology Lab, Berne, Switzerland; and 2AstraZeneca R&D Mo¨ lndal, Mo¨ lndal, Sweden. Purpose: Esomeprazole, the first proton pump inhibitor to be developed for clinical use as an optical isomer, achieves greater and more sustained intragastric acid control than omeprazole. Furthermore, a previous clinical study demonstrated that esomeprazole 40 mg resulted in significantly greater intragastric acid suppression than lansoprazole 30 mg in healthy volunteers. The aim of this study was to compare the effect of repeated once-daily oral dosing of esomeprazole 20 mg and lansoprazole 15 mg on intragastric pH in healthy male and female subjects. Methods: In an open randomized, two-way crossover study, 27 Helicobacter pylori-negative healthy subjects (17 males; mean age: 26 years; mean weight: 70 kg) received esomeprazole 20 mg or lansoprazole 15 mg once in the morning for 5 days with a washout period of at least 14 days. A 24-hour intragastric pH recording was performed using glass electrodes during standardized conditions on day 5 in each period. The percentage of time with intragastric pH ⬎ 4 during the 24-hour period and the 24-hour median intragastric pH were analyzed separately, using a mixed model analysis of variance (ANOVA) with fixed effects for period, sequence and treatment and a random effect for subject within sequence. The mean for each treatment and the mean treatment difference were estimated with 95% confidence intervals (CI). Results: See Table below. No side effects attributable to either study drug were observed. Conclusions: Esomeprazole 20 mg provides more effective intragastric acid control than lansoprazole 15 mg in healthy male and female subjects after repeated doses.

AJG – September, Suppl., 2001

Esomeprazole 20 mg

Abstracts

Lansoprazole 15 mg

Difference

% of 24-hr with pH ⬎ 4* 50.4 (40.7–60.1) 43.0 (33.3–52.8) 7.4 (1.0–13.8) Mean ⫾ SD of the Median 3.7 ⫾ 1.2 3.4 ⫾ 1.2 0.3 ⫾ 1.0 24-hr pH % of subj. with pH ⬎ 4 50 35 for ⱖ12hrs % of subj. with pH⬎4 23 15 for ⱖ16hrs *Mean (95% CI)

p-value 0.026 0.13

137 Esomeprazole 40 mg provides faster and more effective acid control than rabeprazole 20 mg in patients with symptoms of GERD Clive Wilder-Smith MD2*, Catharina Claar-Nilsson RN1, Go¨ ran Hasselgren MD PhD1 and Kerstin Ro¨ hss PhD1. 1AstraZeneca R&D Mo¨ lndal, Mo¨ lndal, Sweden; and 2Gastrointestinal Unit & GI Physiology Lab, Berne, Switzerland. Purpose: Esomeprazole is the first PPI developed as an optical isomer. The aim of this study was to compare the effect on intragastric pH of esomeprazole 40 mg versus rabeprazole 20 mg following single and repeated once daily dosing in patients with symptoms of gastroesophageal reflux disease (GERD). Methods: In an open, randomized, two-way cross-over study, 35 patients with symptoms of GERD (14 males; mean age: 29 years; mean weight:76 kg) received esomeprazole 40 mg or rabeprazole 20 mg once daily in the morning for 5 days, with a wash-out period of at least 14 days between treatments. 24-hr intragastric pH was recorded during standardized conditions on Days 1 and 5 in each period. The percentage of time with intragastric pH ⬎ 4 and median pH during the 24-hr and 4-hr (only Day 1) period following dosing on Days 1 and 5 were analyzed separately, using a mixed model analysis of variance (ANOVA). The mean for each treatment and the mean treatment difference were estimated with 95% confidence intervals (CI). Results: See Table below. No side effects attributable to either drug were observed. Conclusions: Esomeprazole 40 mg provides significantly faster and more effective acid control than rabeprazole 20 mg. Esomeprazole 40 mg (E)

Rabeprazole 20 mg (R)

Difference (E-R)

p-value

Day 1 % of 24-hr with pH ⬎ 4 41.5 (33.7–48.3) 29.4 (22.1–36.7) 11.6 (4.5–18.7) 0.002 24-hr median pH 3.4 (3.0–3.8) 2.7 (2.4–3.1) 0.6 (0.3–1.0) 0.002 % of the first 4 hours 23.2 (15.7–30.8) 11.0 (3.4–18.5) 12.2 (3.7–20.7) 0.006 with pH ⬎ 4 Median pH for the first 2.8 (2.4–3.2) 2.2 (1.8–2.6) 0.5 (0.1–1.0) 0.019 4 hours Day 5 % of 24-hr with pH ⬎ 4 59.4 (52.8–65.9) 44.5 (38.0–51.1) 14.8 (8.1–21.6) ⬍0.0001 24-hr median pH 4.4 (4.1–4.7) 3.5 (3.2–3.9) 0.9 (0.5–1.3) ⬍0.001 All results are presented as mean (95% CI)

138 Bedtime H2 blockers do reduce intragastric acidity long-term and are superior to PPI BID alone Shuwen Xue1, Philip O Katz1*, Amine Hila1 and Donald O Castell1. 1 Medicine, Graduate Hospital, Philadelphia, PA, United States. Purpose: Bedtime H2RA combined with proton pump inhibitor (PPI) twice daily effectively decrease nocturnal gastric acid secretion. However there is still controversy about the development of tolerance on H2RA added to PPI BID regimen.

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Aim: To evaluate the long-term effect of bedtime H2RA plus PPI BID in GERD patients who are failing PPI BID and subsequently treated with new regimen for more than 1 month. Methods: 11 GERD patients who failed PPI BID treatment were put on bedtime H2RA and 24 pH studies were carried on at least 4 weeks after the new regimen. Nocturnal gastric pH and esophageal acid exposure were analyzed. Results: Mean % time intragastric pH ⬎ 4 was 50 ⫾ 21% on PPI BID regimen and 88 ⫾ 17% on PPI BID plus H2RA (p ⫽ 0.0007, paired t test). Mean % time esophageal pH ⬍ 4 was 10.3 ⫾ 17% on PPI BID and 0.8 ⫾ 2.4% on PPI BID plus H2RA (p ⫽ 0.06, mean whitney test). Summary: Adding bedtime H2RA maintained intragastric pH control in GERD patients on H2 RA HS for ⬎4 weeks. Conclusions: 1) Bedtime H2RA CAN be considered for long-term use in patients who need maximal intragastric pH control. 2) Tolerance is NOT universal in these patients.

139 Gastroesophageal reflux disease in renal transplant recipients is commonly associated with H. pylori eradication Cherif M El Younis, MD, FACG*. 1Medicine, SUNY Downstate Medical Center, Brooklyn, NY. Purpose: To study the prevelance of gastroesophageal reflux disease (GERD) among renal transplant recipients and the relationship to the status of H. pylori infection. Methods: Of 279 consecutive renal transplant recipients referred for evaluation of upper GI symtoms, 261 patients underwent esophagogastroduodenoscopy; antral biopsy was obtained for H. pylori testing. All ulcers were biopsied and and a specimen obtained for viral culture. Results: 84 Patients had variable degrees of esophagitis: 39 patients with moderate erythema of the distal esophagus, 31 with erosions, 9 with ulcers, 5 with peptic strictures. 79 patients tested negative for H. pylori (by CLO method). The remianing 5 patients with postive test for H pylori all have mild to moderate esophagitis. The duaration of symtoms ranges from 2 weeks to 11 years after transplantation. Of 84 patients, only 7 gave similar symtoms prior to transplantation. Biopsies and viral cultures from patients with ulcers were negative. 60 patients gave a history of at least one course of antibiostics sometimes in previous two years. Conclusions: 1. Gastroesophageal reflux disease is common in renal transplant recipients. 2. H. pylori infection is rare among renal transplant recipients 3. H. pylori eradication predisposes to severe GERD in renal transplant recipients.

140 Barrett’s esophagus genomic study group: examples of high prevalence Barrett’s esophagus families Teresa G Zais1, Yvonne Romero1*, Enrique Vazquez-Sequeiros1, Alan J Cameron1, Lawrence J Burgart 1, Mary B Fredericksen1, Linda K Wadum1, Raghuram Reddy1, Daniel J Schaid1, Kenneth K Wang1 and Thomas C Smyrk1. 1Gastroenterology-Hepatology, Mayo Foundation, Rochester, MN, United States. Purpose: Families have been reported in which multiple members have Barrett’s Esophagus (BE) and sometimes adenocarcinoma (ACA) in the kinship. Noting the occurrence of BE in successive generations, autosomal dominant inheritance has been proposed. Familial studies could significantly impact the management of relatives of patients with BE, and perhaps interrupt the increasing incidence of esophageal and gastroesophageal junction adenocarcinoma. The Barrett’s Esophagus Genomic Study (BEGS) group, comprised of a multidisciplinary group of physicians from numerous institutions in the United States, South America and Europe, jointly worked on the identification of these high prevalence BE families. Methods: Endoscopically visualized areas of salmon-colored mucosa, which on biopsy showed intestinal metaplasia with goblet cells, were