Purpose: Patients (pts) with short bowel syndrome (SBS) may be dependent on parenteral nutrition and/or intravenous fluid (PN/IV) support. Long-term PN/IV dependence is associated with serious and sometimes fatal complications, including catheter complications, progressive cholestatic liver disease, and other organ failures. Reduction in PN/IV allows SBS pts to be less dependent on daily infusions and may prevent long-term complications. Teduglutide (TED), a human recombinant analog of glucagon-like protein 2, is in development for the treatment of SBS. In a previously reported 24-wk phase III study and its 28-wk extension (CL0600-004/005), 4 pts achieved PN/IV independence (TED 0.05 mg/kg/d n=3, 0.1 mg/kg/d n=1). Baseline characteristics of an additional 7 pts who achieved independence from PN/IV after ≥28 wks of TED treatment in an ongoing long-term study (CL0600-021) are described here. Methods: This is an ongoing, 2-year, open-label, extension study of subcutaneous TED 0.05 mg/kg/d in SBS pts. Pts who completed a 24-wk, phase III, double-blind, randomized, parallel-group, placebo-controlled trial (CL0600-020) were eligible. Results: To date, 7 of 88 pts enrolled in this long-term study have achieved complete independence from PN/IV support. Baseline demographics and disease characteristics varied (Table) with the exception of colon in continuity (5/7 pts) and baseline PN/IV volume of <7 L/wk (6/7 pts). The mean (SD) baseline PN/IV volume for all TED pts in the study was 13.74 (7.30) L/wk. Pts were weaned from PN/IV as early as 28 wks and as late as 101 wks after start of TED. Their adverse event profile was similar to that of the overall study population: diarrhea, nausea, vomiting, and abdominal distension were the most common.Table: [330] TableConclusion: Complete independence from PN/IV support was achieved by a heterogeneous group of SBS pts who received TED for ≥28 wks. An emerging pattern suggests pts achieving independence from PN/IV tend to have colon in continuity and lower baseline PN/IV needs. These data suggest that long term TED treatment is associated with continued improvement in PN/IV weaning. Disclosure: K. Fujioka is a consultant to NPS Pharmaceuticals, Inc. P. Jeppesen has received research support from NPS Pharmaceuticals, Inc. S. O'Keefe has received research support from NPS Pharmaceuticals, Inc. H. Chu is an employee of NPS Pharmaceuticals, Inc. B. Joelsson is an employee of NPS Pharmaceuticals, Inc. P. Berghoefer is an employee of Nycomed: A Takeda Company.

Purpose: Teduglutide has been suggested to improve intestinal fluid absorption in SBS-IF subjects. This study describes the effects of teduglutide when individual components such as parenteral volume, urine volume, and oral fluid intake are utilized to comprehensively characterize the effect of teduglutide on intestinal fluid absorption. Methods: The FCE has been defined as Parenteral Volume + Oral Fluid Volume - Urine Volume. This was calculated in study CL0600-020 after an initial optimization and stabilization period occurred to establish a stable baseline urine volume, a surrogate marker for intestinal fluid absorption. FCE was calculated to compare teduglutide 0.05 mg/kg/d subcutaneously (SC) vs placebo, as well as PS volume alone. Results: At week 24 in study CL0600-020, FCE changes were respectively -5.4 L/wk with teduglutide (n=39) and -1.1 L/wk with placebo (n=39) compared to -2.3 L/wk with placebo and -4.4 L/wk with teduglutide using just reduction in PS volume. The FCE and PS volume reduction, which characterize the effects of teduglutide, are shown from weeks 4 to 24 in Figure 1.Figure: No Caption available.Conclusion: In a well-controlled trial of adult SBS-IF subjects utilizing the FCE as a measure of direct intestinal absorption, teduglutide is shown to significantly improve absorption when compared with placebo. Calculating the FCE by combining these 3 easily measurable clinical parameters provides a more comprehensive measurement than measuring PS reduction only. The FCE may reflect the true effect of the novel GLP-2 analog, teduglutide, and allow more appropriate monitoring by practitioners who manage complex SBS-IF patients. Disclosure: Dr. Jeppesen - Consultant: NPS Pharmaceuticals, Consultant: Nycomed GmbH Dr. Pertkiewicz - Consultant: NPS Pharmaceuticals, Member of Advisory Board: Nutricia Scientific Foundation, Lectures at Teaching Workshops Dr. Fujioka: No financial relationships to report Dr. Boullata - PI: NPS Pharmaceuticals Dr. Berghoefer - Employee: Nycomed GmbH Dr. Joelsson - Employee: NPS Pharmaceuticals.

OBJECTIVE:To investigate the efficacy of pantoprazole 20 mg once daily (o.d.) in relieving epigastric pain associated with ulcer-like functional dyspepsia.RESEARCH DESIGN AND METHODS:In this double-blind, placebo-controlled, multicentre study, patients experiencing ulcer-like functional dyspepsia, with epigastric pain as the predominant symptom, were randomised to receive pantoprazole 20 mg or placebo o.d. for 28 days. Primary endpoint was the complete relief (i.e. absence) from epigastric pain after 28 days' treatment. The odds ratio (OR) for pantoprazole/placebo and its 95% confidence intervals (CIs) were determined. Significant superiority of pantoprazole was concluded if the value 1.0 was above this interval.RESULTS:Of 419 patients (intention-to-treat [ITT]) randomised to treatment, 207 received pantoprazole and 212 received placebo. Epigastric pain relief was achieved after 28 days' treatment in 55% of pantoprazole recipients and 45% of placebo recipients (per-protocol [PP]: 58% and 47%, respectively). Pantoprazole demonstrated statistically significant superiority compared with placebo in the ITT (OR: 0.68; 95% CI: 0.46-0.99) and PP populations (OR: 0.64; 95% CI: 0.42-0.98). Pantoprazole was more efficacious than placebo in relieving heartburn and acid regurgitation after 7, 14 and 28 days of treatment. The sum score of gastrointestinal symptoms after 28 days was statistically significantly lower in the pantoprazole than placebo group. Fewer patients receiving concomitant psychotropic medication experienced relief from epigastric pain than those not receiving such medication. Adverse events did not significantly differ between pantoprazole and placebo.CONCLUSIONS:Results of this study suggest that pantoprazole 20 mg is more efficacious than placebo, and is a well-tolerated treatment for relieving epigastric pain in patients with ulcer-like functional dyspepsia. Further research is needed to confirm these findings.

Background: On-demand PPI has been shown to be an effective step-down therapy for GERD.But data on comparison with regular PPI is lacking.Aim: To compare the efficacy, quality of life (QoL) and cost-effectiveness of on-demand and daily PPI regimens in long-term management of mild GERD.Methods: Consecutive patients with weekly reflux symptoms for >6 months were prospectively recruited for assessment of reflux symptom score (0-3) and validated disease-specific GERD-QOL questionnaire (0-400).EGD defined esophagitis by LA classification.Exclusion criteria included NSAID use, peptic ulcer, esophagitis ≥ grade B, stricture or Barrett's esophagus.Eligible patients were given esomeprazole (Eso) 20 mg daily for 8 weeks as initial treatment.Patients with complete symptom resolution to Eso were randomized to (1) On-demand (OD) group: daily placebo + on-demand Eso 20 mg, or (2) Regular (R) group: daily Eso 20mg + on-demand placebo for 26 weeks.Treatment failure was defined as inadequate relief of reflux symptom by patient-reported global symptom assessment.Primary measure was treatment failure at 26 weeks.Results: 250 patients (Male= 87, Mean age: 51+/-11, NERD=205) were randomized (N=125 in each group).37 (29.6%)patients in OD and 22 (17.6%) in R group had treatment failure at 26 weeks (p=0.025).The probability of treatment failure at 26 weeks was 31.6% (mean remission time: 21 weeks) for OD and 19.0% (mean remission time: 24 weeks) for R group, respectively (p=0.018, log rank).Among OD patients without treatment failure, PPI was taken in 20.5% of time and there was no significant difference in symptom severity (Median symptom score: 1, p= 0.34) or GERD-specific QoL measures (OD: 210.8 +/-91.4Vs R: 196.0 +/-101.1,p=0.43) at 26 weeks compared to R patients.The cost-effectiveness ratio was US$15,144 for OD group and US$59,289 for R group.The incremental cost to achieve an additional patient with adequate symptom relief by switching from OD group to R group was US$318,272.Conclusion: On-demand PPI regimen is inferior to daily PPI regimen for long-term management of mild GERD.However, on-demand PPI strategy is much more cost-effective.Probability of treatment failure over 26 weeks

a linear combination of symptoms: ES (sialorrhea, globus, dysphagia, odinophagia, retching, eructs, and halitosis), UA (upper abdominal discomfort, early satiety, postprandial fullness, nausea and flatulence), EX (non-cardiac chest pain, disnea, chronic cough, hoarseness, sleep disturbances).Scores from the extracted variance (UA 48%, ES 40%, EX 46%) were used in a general linear model (GLM) adjusted by geographical distribution, medical specialty, age, sex, BMI, severity of heartburn and regurgitation.RESULTS: Severities of ES, UA, and EX symptoms were positively associated with the severity of heartburn and regurgitation.EX symptoms scores were higher in the NS group compared with diurnal complains group (p<0.001),but for UA, the symptoms score was higher in the diurnal group (p<0.03).We tested the effect of NS over ES, UA and EX scores using a GLM for repeated measurements (adjusted by geographical distribution, medical specialty, age, sex, and BMI).Improvements in the scores for all symptoms were found after treatment with PMg.The EX symptoms in NS group had particularly relevant improvement (p<0.001).CONCLUSIONS: PMg showed an important improvement for all symptoms scores.This effect was markedly superior for EX symptoms in the NS group.

determinant of QoL in both genders, other upper GI symptoms also contribute to GERD related QoL impairment in female patients.Gender difference in symptom determinants of different domains of GERD-QoL M1030

Purpose: Sleep disturbance in GERD patients impairs quality of life and reduces work productivity. Over- and under-reporting of symptoms before, during and after therapeutic intervention is a well-known phenomenon in daily clinical practice. We systematically assessed sleep disturbance in a GERD trial utilizing assessment by the investigator and ReQuest™, a validated sensitive tool for the evaluation of GERD symptoms. Methods: In this open, multinational, multicenter trial 633 GERD patients were treated with pantoprazole 40 mg daily for 28 days. For the assessment of GERD symptoms patients completed ReQuest™ daily, while the investigator assessment was performed at day 0, 14 and 28. The proportion of patients troubled by sleep disturbance on all of the 7 consecutive days prior to day 0, 14 and 28 was compared between patient self-assessment with ReQuest™ and investigator assessment and 95% confidence intervals were calculated. Results: The comparison of point estimates and confidence intervals for the proportion of patients (PP; nequals; 538) yielded a statistically significant difference at baseline, during and after therapy between the two modes of assessment. Conclusion: There is a discrepancy between investigator and patient symptom assessment regarding the proportion of GERD patients with sleep disturbance. The reduction of these numbers over time is similar comparing the two assessment modes. The significantly lower proportion of patients assessed as suffering from sleep disturbance according to investigator assessment may be due to underestimation of symptoms by the investigator. Thus, investigator assessment alone may not be the optimal means to evaluate sleep disturbance (and other symptoms) in GERD patients, as underestimation of symptoms may lead to inappropriate therapeutic decisions. These data may also suggest that prolonged PPI treatment might be required to properly improve GERD related sleep disturbance.Table: Proportion of Patients Suffering from Sleep Disturbance (%; CI 95%)

Background/Aims: The growing importance of symptom assessment is evident from the numerous clinical studies on gastroesophageal reflux disease (GERD) assessing treatment-induced symptom relief. However, to date, the a priori selection of criteria defining symptom relief has been arbitrary. The present study was designed to prospectively identify GERD symptom thresholds for the broad spectrum of GERD-related symptoms assessed by the validated reflux questionnaire (ReQuest (TM)) and its subscales, ReQuest (TM)-GI (gastrointestinal symptoms) and ReQuest (TM)-WSO (general well-being, sleep disturbances, other complaints), in individuals without evidence of GERD. Methods: In this 4-day evaluation in Germany, 385 individuals without evidence of GERD were included. On the first day, participants completed the ReQuest (TM), the Gastrointestinal Symptom Rating Scale, and the Psychological General Well-Being scale. On the other days, participants filled in the ReQuest (TM) only. GERD symptom thresholds were calculated for ReQuest (TM) and its subscales, based on the respective 90th percentiles. Results: GERD symptom thresholds were 3.37 for ReQuest (TM), 0.95 for ReQuest (TM)-GI, and 2.46 for ReQuest (TM)-WSO. Conclusion: Even individuals without evidence of GERD may experience some mild symptoms that are commonly ascribed to GERD. GERD symptom thresholds derived in this study can be used to define the global symptom relief in patients with GERD.

Purpose: It is controversial if non-erosive reflux disease (NERD) and erosive esophagitis (EE) form a continuum of a single disease or if they are manifestations of two different pathophysiological disease entities. We therefore reviewed the ReQuest™ database (of patients with well characterized reflux disease) to determine the proportions of male and female patients with NERD and with EE of different grades of severity. Methods: The ReQuest™ database contains data from 2 NERD and 12 EE clinical trials with symptom assessment based on the reflux questionnaire ReQuest™. 10 EE clinical trials enrolled patients with severity grades A-D, the other 2 EE studies included patients with severity grades B-D (Los Angeles classification). Baseline demographics and characteristics of 6,810 per-protocol patients were analyzed. Results: Of these patients, 964 had NERD and 5,846 suffered from EE [grade A: 2,309 (33.9%); grade B: 2,755 (40.5%); grade C: 637 (9.4%); grade D: 145 (2.1%)]. A greater proportion of NERD patients were females (61.3%). More females with EE had mild disease (grade A), whereas a higher proportion of male patients had more severe disease (grades C and D). Conclusions: GERD in females is characterized by a higher proportion of NERD compared with men; and when EE is present, the proportion of a mild disease course (grade A) is also higher than in men. The fact that women presenting with GERD symptoms have less severe alteration of the esophageal mucosa, raises the possibility that this observation reflects genetically determined differences in visceral sensitivity amongst men and women to exposure of gastroesophageal reflux.Table 1: Baseline demographics of GERD clinical patientsTable 2: Baseline distribution of EE severity grades depending on gender