Six month safety and tolerability of esomeprazole as maintenance therapy in GERD patients with healed erosive esophagitis (EE)

April 2000

5929 LEWIS ANTIGEN PHENOTYPE IS ALTERED IN HELICOBACTER PYLORI ISOLATED FROM ASYMPTOMATIC SUBJECTS, David A. Rasko, Monika Keelan, Alan B. Thomson, Diane E. Taylor, Univ of Alberta, Edmonton, AB, Canada. The role of Lewis antigens in the pathogenic process is not well understood. The aim of this study was to determine whether the Lewis antigen expression of H. pylori differed in isolates obtained from symptomatic and asymptomatic individuals. Lewis antigen expression status was determined by ELISA, and confirmation of LPS 0 side chain production in isolates not expressing Lewis antigen phenotype was conducted by SDS-PAGE. Expression of Lewis antigens by H. pylori isolates of symptomatic and asymptomatic individuals differed significantly in three main categories: I) Type I Lewis antigens (Lea and Le b ) were not expressed at all by isolates from asymptomatic individuals, as compared with low level expression by isolates from symptomatic individuals; 2)incidence of LeX expression was significantly reduced in isolates from asymptomatic individuals; 3) an increased proportion of isolates from asymptomatic individuals did not express any Lewis antigens at all. The identification of differences between H. pylori isolated from symptomatic and asymptomatic individuals is the first step to understanding the potential role Lewis antigens may play in the pathogenicity of this bacteria. The decrease in the LeX expression by isolates from asymptomatic individuals is particularly interesting as this antigen has been noted to be expressed in higher proportions of H. pylori isolated from patients with peptic ulcer disease. The isolation of a high proportion of H. pylori that do not express any Lewis antigens in asymptomatic strains may also indicate a host-mediated cross reaction to the H. pylori Lewis antigens that may cause the pathology seen in some symptomatic patients.

5930 INFLUENCE OF LANSOPRAZOLE ON THE HUMAN GASTRIC LIPASE AND THE INTRAGASTRIC LIPOLYSIS IN HEALTHY VOLUNTEERS. Christophe Renou, Eric Ville, Frederic Carriere, Philippe Grandval, Maryse Joubert-Collin, Rene Laugier, Hosp de la Timone, Marseille, France; Cnrs-Lle, Marseille, France; Lab TAKEDA, Puteaux, France. Lansoprazole is a substituted benzimidazole which selectively inhibits the H+/K+-ATPase of the parietal cells of the stomach. Although human gastric lipase (HGL) is only produced by the chief cells of the stomach, the possibility of an interaction between lansoprazole and HGL has never been evaluated in humans. The aim of this study was to estimate the influence of lansoprazole on HGL concentration and output, as well as on gastric lipolysis in healthy volunteers. Methods: six healthy volunteers were intubated with a gastric tube and a duodenal tube located in the second duodenum to perform gastric and duodenal samples after a standard liquid test meal administration (Shak Iso, 375 ml) without lansoprazole (Test A) or after seven days of treatment (Test B). Healthy volunteers were randomized in 2 groups: the 2 tests of 3 healthy volunteers of group I were performed before and after seven days of treatment whereas the 3 other healthy volunteers of group 2 had the first test at the end of treatment and the second after 2 weeks of a wash-out period. Lipase activity was measured using a pH-stat and lipolysis products were quantified by thin layer chromatography. The intragastric hydrolysis level was defined as the percentage of acyl chains released from the meal triglycerides. Calculation of the HGL pyloric output and overall lypolysis in the stomach was based on the recovery of a non-absorbable marker (PEG, IOgll) present into the meal. Results: the pH of the gastric contents was higher in Test B than in Test A with mean values of 4.55+1-1.92 and 2.57+1-1.86, respectively, at the end of the gastric emptying. Lipase activity (U/ml) reported to time or to meal gastric emptying was comparable in the two tests. Moreover, there was not statistical differences between Test B and Test A concerning the HGL pyloric output and the overall lipolysis in the stomach. The half-times for gastric emptying of the meal were similar in the two groups. Conclusion: I) Lansoprazole enhanced the intragastric pH. 2) lansoprazole did change neither the rate of gastric emptying, the activity and the pyloric gastric output of HGL nor the intragastric lipolysis during liquid test meal in healthy volunteers.

5931 EFFECT OF REBAMIPIDE ON THE GASTRIC MUCOSAL IMMUNE RESPONSE IN PATIENTS WITH HELICOBACTER PYLORI INFECTION. Jong-Sun Rew, Young-Eun Joo, Hyun-Soo Kim, Sei-Jong Kim, HyunChul Lee, Suck-Chei Choi, Young-Ho Nah, Soo-Teik Lee, Chan-Guk Park, Man-Woo Kim, Chonnam National Univ Med Sch, Kwangju, South Korea; Wonkwang Univ Sch of Medicine & Hosp, Iksan, South Korea; Chonbuk National Univ Med Sch, Chonju, South Korea; Chosun Univ ColI of Medicine, Kwangju, South Korea. Background/Aims: Gastric infection with H. pylori is now recognized as the leading cause of chronic gastritis and ulcer disease. The aim of this study was to compare the additive effect of rebamipide with that of

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teprenone after eradication of H. pylori with changes of various inflammatory parameters. The relative contribution of local T helper cell response of the Thl-type and Th-2 type to the pathogengesis of gastritis and gastric ulcer associated with H. pylori infection have been examined. Methods: A total of 52 H. pylori positive gastritis or gastric ulcer patients were treated with omeprazole, ampicillin and metronidazole for 2 weeks, and they were assigned at random to two groups; Group I received rebamipide IOOmg thrice daily for 6 weeks, while Group II received teprenone 50mg thrice daily for 6 weeks. We evaluated clinical symptoms every two weeks. Gastric mucosal biopsy samples were also taken for assessment of the presence of H. pylori and the analysis of cytokines and the degree of inflammatory cell infiltration before and after treatment. IL-l¥a, IL-8, IL-IO and IL-12 were evaluated by the enzyme linked immunosorbent assay(ELISA). H. pylori status was determined by histology and the rapid urea test, with gastritis scored using the Sidney system. Results: Symptom scores and the degree of infiltrative inflammatory cell in gastric mucosa were markedly reduced(p0.05). No statistically significant correlations between the degree of gastritis and cytokine secretion in antral mucosa were noted. Conclusions: These results indicated that rebamipide seems to promote local gastric Th2-associated immune response in H. pylori positive gastritis or gastric ulcer.

5932 SIX MONTH SAFETY AND TOLERABILITY OF ESOMEPRAZOLE AS MAINTENANCE THERAPY IN GERD PATIENTS WITH HEALED EROSIVE ESOPHAGITIS (EE). Joel E. Richter, David A. Johnson, David 1. Magner, Wendy Skammer, Kathleen Spreen, Cleveland Clin Fdn, Cleveland, OH; Eastern, VA Sch of Medicine (EVMS), Norfolk, VA; AstraZeneca LP, Wayne, PA. Objective: To assess the safety and tolerability of long-term treatment with esomeprazole (an optical isomer of omeprazole) in doses of 40 mg (E40), 20 mg (E20), and 10 mg (EIO), once daily, compared with placebo (P) in maintenance of healed EE. Methods: In a pooled analysis of 2 identically designed US, multicenter, randomized, double-blind, P-controlled trials, 688 patients with EGO-confirmed healed EE (Los Angeles Classification = "Not Present") and H pylori-negative by histology, were enrolled following completion of a comparative trial of healing efficacy with E40, E20, and omeprazole 20 mg (020). In the present studies patients received E40, E20, EIO, or P for up to 6 months. EGD, adverse events (AEs), laboratory, and physical assessments were performed at baseline, and 1, 3, and 6 months after start of maintenance therapy. Results: 345 patients completed 6 months' treatment (129, 131,85, and 33 patients in the E40, E20, ElO, and placebo groups, respectively). Discontinuation in the P group was primarily due to lack of therapeutic response (63.9%). Median duration of exposure for each of the 4 treatment groups was 173, 174, 165, and 30 days for E40, E20, ElO, and P, respectively. The 3 most common AEs in patients treated with esomeprazole were respiratory infection (8.5%), diarrhea (6.7%), and headache (6.6%). These AEs were also the most common for P. There was no suggestion of a time-dependent trend in the occurrence of AEs. AEs deemed by investigators to be related to treatment were comparable in the active and P groups (E=21.9%, P=20.8%). There were no meaningful differences between the groups when examined by age, race, or gender. As expected in patients on antisecretory therapy, increases in serum gastrin were observed. Mean increases were 50.79 pg/mL and 22.08 pglmL for patients taking E40 and E20, respectively, and reached a plateau within 2-3 months. Mean decreases of 2.95 pg/mL and 32.59 pg/mL were observed for patients taking EIO and P, respectively. These decreases were not unexpected since baseline values were elevated due to receiving daily doses of E40, E20, or 020 in the healing phase of the trial. Serum gastrin returned to baseline within 4 weeks after discontinuation of therapy. Mean changes in other laboratory tests represented only a small shift within the normal range. There were no clinically meaningful changes in HP, pulse rate, or body weight. Conclusions: Daily administration of E40, E20, and ElO, for up to 6 months to patients with healed EE was well tolerated.