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Su1374 Differences in Nutrient Intake Between Irritable Bowel Syndrome (IBS) Patients and Healthy Volunteers
* Change from baseline (1)P-values are from paired t-tests comparing follow-up score to baseline within each treatment. (2)P-values and 2-sided CIs are from generalized linear models with the baseline score as a covariate. Table # 2: Individual IBS Syndrome of Symptoms Intensity Scores - mITT Population
*p-values are from Wilcoxon rank sum tests comparing the distribution of change categories between treatments Su1374 Differences in Nutrient Intake Between Irritable Bowel Syndrome (IBS) Patients and Healthy Volunteers Marisa A. Spencer, William D. Chey, Simon J. Evans, Theresa Han-Markey, Sarah Ball, Shanti L. Eswaran
* Change from baseline (1)P-values are from paired t-tests comparing follow-up score to baseline within each treatment. (2)P-values and 2-sided CIs are from generalized linear models with the baseline score as a covariate.
Background: Irritable Bowel Syndrome (IBS) patients often associate their symptoms with eating food. Diets low in gluten and FODMAPs may improve IBS symptoms. Little is known about baseline nutrient intake in IBS patients and how this compares with healthy individuals. Aim: To compare baseline nutrient intake between IBS patients and healthy controls. Methods: We assessed baseline nutrient intake in IBS with diarrhea (IBS-D) patients (Rome III) and healthy controls from the US utilizing 3-7 day food diaries collected as part of an ongoing randomized, controlled trial assessing the role of the low FODMAP diet in IBS. Data regarding demographics, total calories, protein, fat, and carbohydrate intake were analyzed. We also assessed FODMAP and grain intake. Multivariate regression analysis was used to determine significant differences between the IBS and control populations after adjusting for total caloric intake, age, gender, and body mass index (BMI). Results: Diary data from 58 IBS-D patients and 73 healthy controls were included. Mean age of the groups was similar [IBS = 45.1 years old (range 21-74), Controls = 45.9 years old (range 23-80)]. The proportion of females in the study groups was similar (IBS = 66.1%, Controls = 60.3%). Total caloric intake was similar between groups after adjusting for age, gender, and BMI (IBS= 1929 kcal/ day, Controls = 1948 kcal/day). However, BMI was significantly higher in IBS patients than controls (28.6 versus 26.1 respectively, p = 0.001). There were no significant differences in total protein, fat, or carbohydrate intake between the 2 groups. Regarding FODMAPs, IBS patients consumed 40% less lactose than controls (p=0.025). IBS patients also consumed 60% less total polyols than controls (p<0.001) [Table 1]. Between group differences were
Su1373 Ibgard®, a Novel Small Intestine Targeted Delivery System of Peppermint Oil, Results in Significant Improvement in Severe and Unbearable IBS Symptom Intensity. Results From a US Based, 4-Week, Randomized, Placebo-Controlled, Multi-Center Ibsrest™ Trial Brooks D. Cash, Michael S. Epstein, Syed M. Shah Background: Up to 43% of patients with IBS describe their symptoms as severe and represent an unmet need. Derangements in gut immunity, microbiota, sensation, motility, secretion, and digestion have all been proposed as possible etiologies of irritable bowel syndrome (IBS). L-menthol, the main constituent of peppermint oil (PO), has anti-spasmodic, anticarminative, topical analgesic, anti-infective and 5-HT3 receptor antagonism properties, making it a plausible IBS therapy for this unmet need. The Irritable Bowel Syndrome Reduction Evaluation and Safety Trial (IBSREST™) was conducted to evaluate the efficacy and tolerability of IBgard, an ultra-purified PO for sustained release in the small intestine, in a population enriched with severe/unbearable symptoms. Methods: Subjects were 1860 years of age, met Rome III criteria for IBS-D or IBS-M, had average daily IBS-related
S-489
AGA Abstracts
AGA Abstracts
abdominal pain of ≥4 on a 0-10 scale, and a Total IBS Symptom Score (TISS) of ≥2 on a 0-4 scale. After a 3-week period for symptom severity assessment and prohibited medication washout, subjects were randomly allocated to receive IBgard 180 mg TID or identical placebo for 4 weeks. Efficacy variables included change from baseline in intensity of IBS symptoms rated as severe/unbearable by subjects. Safety assessment included treatment-emergent adverse events (TEAE). Results: 72 subjects (mean 40.7 years, 75% female, 77.8% white) were randomized to IBgard (n=35) or placebo (n=37). 52.8% had IBS-D and 47.2% IBSM. Using mITT analysis, there was a statistically significant decrease from baseline in the IBgard arm (-4.12), as compared to placebo (-2.00), in the number of severe/unbearable symptoms after 28 days (p=.0063). Compared to placebo, subjects receiving IBgard had statistically significant improvement from baseline in abdominal pain/discomfort (p=.0015), abdominal bloating/distension (p=.0036) and incomplete evacuation (p=.0038) (Table). Compared to baseline, after 24 hours there was a 39% decrease (p<.0001) and after 28 days there was an 80% decrease (p<.0001) in severe/unbearable symptoms with IBgard. After 28 days, subjects randomized to IBgard reported significant improvement in all IBS symptoms rated as severe/unbearable at baseline (all p-values ≤.0027): abdominal pain/ discomfort, abdominal bloating/distension, constipation, diarrhea, pain at evacuation, passage of gas/mucus, urgency and incomplete evacuation. IBgard was well tolerated and no patients discontinued due to a TEAE. Conclusions: IBgard, a unique formulation of ultra-purified PO, had a statistically significant reduction, compared to placebo, in the number of IBS symptoms rated as severe or unbearable over 4 weeks. IBgard was significantly better than placebo in reducing severe or unbearable abdominal pain, abdominal bloating, and sense of incomplete evacuation. IBgard was safe and well tolerated. Severe or Unbearable Intensity Scores of Total and Individual Symptoms - mITT Population
Table # 1: Individual IBS Syndrome of Symptoms Frequency Scores - mITT Population
AGA Abstracts
significant for individual polyols: mannitol (p=0.002), sorbitol (p<0.001), and xylitol (p= 0.014). There was no significant difference in intake of fructose, constituent lipids, total fiber, or total grains between the 2 groups. However, IBS patients consumed significantly more whole grain flour (p=0.028) and whole grain bread (p=0.001) than controls, but similar amounts of refined flour and refined flour bread. Conclusions: IBS-D patients consumed less FODMAPs including lactose and polyols than healthy controls. Whether this is due to IBS patients consciously or unconsciously avoiding foods that trigger their symptoms remains unclear. On the other hand, IBS patients consumed more whole grains. These data suggest that many IBS-D patients alter their dietary FODMAP and grain intake and may prove useful when counseling IBS patients on dietary interventions.
Table 1: Subjects' demographics and healthcare costs
Su1375 Healthcare Cost of Irritable Bowel Syndrome Based on Self-Reported Questionnaires in an Asian Cohort Yu Tien Wang, Andrew Ming Liang Ong, Jing Zeng, Sylvaine Barbier, Bibhas Chakraborty, Van Hai Nguyen
*GLM analysis: p<0.05
Introduction Irritable bowel syndrome (IBS) – a chronic functional disorder that affects 10-20% of the population worldwide – is detrimental to patients' quality of life and imposes substantial healthcare costs. While the extent of IBS's economic burden is well characterized in Western countries, this information is scarce in Asian countries. Aim To characterize healthcare cost from the Asian IBS patient's perspective. Method Self-administered questionnaires were delivered to participants in an IBS public forum in Singapore in august 2014. Diagnosis of IBS was based on subjects' self report of IBS diagnosis by physicians while IBS subtypes were based on ROME III criteria. Healthcare costs were assessed using a validated questionnaire module which interrogates direct and indirect health care costs as well as its sources. Direct costs of IBS include cost of hospitalizations, outpatient medical visits, and non-prescription treatment. Indirect costs include cost of missed work days (assumed to be Singapore dollars S$150/day) and costs associated with days being unable to perform usual duties (assumed to be S$50/day). All costs are presented in US$ using current exchange rate (S$1 = US$0.8). Statistical analysis of costs The average costs were stratified by age, gender, IBS type, and IBS symptom frequency to study their potential differences. The differences in costs between these subgroups were assessed using standard statistical comparison tests (i.e. two sample t-tests and Wilcoxon-Mann-Whitney two-sample tests). A multivariate GLM regression was estimated to identify patient's characteristics that are associated with higher total IBS costs. All statistical analyses were performed using STATA version 13 (Stata Corp, College Station, Texas). Result 256 participants attended the forum and 155 questionnaires were returned. Of these, 92 subjects reported diagnosis of IBS. Among them, 73% were female, 51% were current married and the predominant (88%) ethnic group was Chinese. The subjects' demographics and healthcare costs are presented in table 1. Based on GLM regression analysis, IBS patients have higher health care costs if being male, being married, having IBS symptoms more than once a week and being in the age group of 3544. Conclusion IBS in this cohort of Singaporean patients was associated with significant healthcare costs of around US$2,000 per patient per year. This healthcare burden is large, more than twice the nation's per capita average healthcare expenditure. The majority of the expenses were related to outpatient medical care but there were also significant expenses incurred through non-prescription treatments and indirect costs. Characteristics which predicted higher healthcare costs were male, being married, more frequent symptoms and age between 35-44. Further research is required to identify cost-effective IBS management.
Su1376 Assessment of IBS-D Severity: A Case Study From Two Randomized, DoubleBlind, Placebo-Controlled Pivotal Trials to Evaluate the Efficacy of Oral Ibodutant Jan F. Tack, Simona Scartoni, Giulia Tonini, Kai Schumacher, Monica Bertolotti, Alessandra Nuti, Kerstin Ott, Grazia Simona Cera, Angela Capriati, Carlo A. Maggi Introduction Assessment of the severity of symptoms is fundamental to select Irritable Bowel Syndrome (IBS) patients for inclusion in pivotal trials. In addition to diagnostic Rome III criteria, regulatory guidelines recommend precise severity level for the eligibility of patients (customized by IBS-subtypes), based on scale assessments to be daily recorded by patients during a 2 week run-in period. Severity score of IBS symptoms can also be recorded by the validated IBS-Symptom Severity Score (IBS-SSS) questionnaire. Two ongoing pivotal trials testing ibodutant, a selective and potent antagonist of neurokinin 2 receptors for IBS with Diarrhea (IBS-D), evaluate symptoms severity trough both methods. Aim Evaluation of the correlation between eligibility severity criteria as per regulatory guidelines and severity assessment from IBS-SSS questionnaire. Methods Two double blind, randomized, placebo controlled, Phase III studies are running to evaluate the efficacy and safety of 10 mg oral ibodutant in female patients with IBS-D. After a screening visit, patients undergo a 2-week run-in period (no rescue medication allowed) to confirm all eligibility criteria, including IBS severity based on the severity of abdominal pain (0-10 scale), number of bowel movements and stool consistency, daily recorded through the e-diary questionnaire (e-PRO). IBS severity is also evaluated by IBS-SSS questionnaire (score severity: <175 Mild; >175-300 Moderate; >300 Severe) at the start of run-in (and repeated at the end only for randomized patients). Results Among the 948 female patients who underwent run-in, 665 reported severe IBS symptoms as per IBS-SSS score versus 283 resulting mild/moderate at the start of runin. Based on the 2-week e-PRO results, 612 patients met severity eligibility criteria for randomization, against 336 patients who did not meet them. Table 1 shows that 49.4% of patients resulted to be severe as per IBS-SSS at the start of run-in, and met the eligibility severity criteria as per e-PRO during run-in, whereas 14.7% with mild/moderate IBS-SSS were also not eligible for e-PRO severity. However, a high percentage (35.9%) of patients showed no-concordance between the two methods used. When IBS-SSS was compared only to the severity of pain recorded on e-PRO, the concordance increases to 73%. The concordance between the IBS-SSS questionnaires administered at start and end of the run-in was reported in 82% of randomized patients (Table 2). Conclusion IBS-SSS questionnaire cannot replace e-diary assessment during the 2 week run-in period to determine eligibility of patients to clinical trials as per regulatory requirements for IBS severity. Table 1
*not all the patients resulting eligible for severity were finally randomized and provided a second IBS-SSS (screen failures due to other reason than severity)
AGA Abstracts
S-490
*p-values are from Wilcoxon rank sum tests comparing the distribution of change categories between treatments Su1374 Differences in Nutrient Intake Between Irritable Bowel Syndrome (IBS) Patients and Healthy Volunteers Marisa A. Spencer, William D. Chey, Simon J. Evans, Theresa Han-Markey, Sarah Ball, Shanti L. Eswaran
* Change from baseline (1)P-values are from paired t-tests comparing follow-up score to baseline within each treatment. (2)P-values and 2-sided CIs are from generalized linear models with the baseline score as a covariate.
Background: Irritable Bowel Syndrome (IBS) patients often associate their symptoms with eating food. Diets low in gluten and FODMAPs may improve IBS symptoms. Little is known about baseline nutrient intake in IBS patients and how this compares with healthy individuals. Aim: To compare baseline nutrient intake between IBS patients and healthy controls. Methods: We assessed baseline nutrient intake in IBS with diarrhea (IBS-D) patients (Rome III) and healthy controls from the US utilizing 3-7 day food diaries collected as part of an ongoing randomized, controlled trial assessing the role of the low FODMAP diet in IBS. Data regarding demographics, total calories, protein, fat, and carbohydrate intake were analyzed. We also assessed FODMAP and grain intake. Multivariate regression analysis was used to determine significant differences between the IBS and control populations after adjusting for total caloric intake, age, gender, and body mass index (BMI). Results: Diary data from 58 IBS-D patients and 73 healthy controls were included. Mean age of the groups was similar [IBS = 45.1 years old (range 21-74), Controls = 45.9 years old (range 23-80)]. The proportion of females in the study groups was similar (IBS = 66.1%, Controls = 60.3%). Total caloric intake was similar between groups after adjusting for age, gender, and BMI (IBS= 1929 kcal/ day, Controls = 1948 kcal/day). However, BMI was significantly higher in IBS patients than controls (28.6 versus 26.1 respectively, p = 0.001). There were no significant differences in total protein, fat, or carbohydrate intake between the 2 groups. Regarding FODMAPs, IBS patients consumed 40% less lactose than controls (p=0.025). IBS patients also consumed 60% less total polyols than controls (p<0.001) [Table 1]. Between group differences were
Su1373 Ibgard®, a Novel Small Intestine Targeted Delivery System of Peppermint Oil, Results in Significant Improvement in Severe and Unbearable IBS Symptom Intensity. Results From a US Based, 4-Week, Randomized, Placebo-Controlled, Multi-Center Ibsrest™ Trial Brooks D. Cash, Michael S. Epstein, Syed M. Shah Background: Up to 43% of patients with IBS describe their symptoms as severe and represent an unmet need. Derangements in gut immunity, microbiota, sensation, motility, secretion, and digestion have all been proposed as possible etiologies of irritable bowel syndrome (IBS). L-menthol, the main constituent of peppermint oil (PO), has anti-spasmodic, anticarminative, topical analgesic, anti-infective and 5-HT3 receptor antagonism properties, making it a plausible IBS therapy for this unmet need. The Irritable Bowel Syndrome Reduction Evaluation and Safety Trial (IBSREST™) was conducted to evaluate the efficacy and tolerability of IBgard, an ultra-purified PO for sustained release in the small intestine, in a population enriched with severe/unbearable symptoms. Methods: Subjects were 1860 years of age, met Rome III criteria for IBS-D or IBS-M, had average daily IBS-related
S-489
AGA Abstracts
AGA Abstracts
abdominal pain of ≥4 on a 0-10 scale, and a Total IBS Symptom Score (TISS) of ≥2 on a 0-4 scale. After a 3-week period for symptom severity assessment and prohibited medication washout, subjects were randomly allocated to receive IBgard 180 mg TID or identical placebo for 4 weeks. Efficacy variables included change from baseline in intensity of IBS symptoms rated as severe/unbearable by subjects. Safety assessment included treatment-emergent adverse events (TEAE). Results: 72 subjects (mean 40.7 years, 75% female, 77.8% white) were randomized to IBgard (n=35) or placebo (n=37). 52.8% had IBS-D and 47.2% IBSM. Using mITT analysis, there was a statistically significant decrease from baseline in the IBgard arm (-4.12), as compared to placebo (-2.00), in the number of severe/unbearable symptoms after 28 days (p=.0063). Compared to placebo, subjects receiving IBgard had statistically significant improvement from baseline in abdominal pain/discomfort (p=.0015), abdominal bloating/distension (p=.0036) and incomplete evacuation (p=.0038) (Table). Compared to baseline, after 24 hours there was a 39% decrease (p<.0001) and after 28 days there was an 80% decrease (p<.0001) in severe/unbearable symptoms with IBgard. After 28 days, subjects randomized to IBgard reported significant improvement in all IBS symptoms rated as severe/unbearable at baseline (all p-values ≤.0027): abdominal pain/ discomfort, abdominal bloating/distension, constipation, diarrhea, pain at evacuation, passage of gas/mucus, urgency and incomplete evacuation. IBgard was well tolerated and no patients discontinued due to a TEAE. Conclusions: IBgard, a unique formulation of ultra-purified PO, had a statistically significant reduction, compared to placebo, in the number of IBS symptoms rated as severe or unbearable over 4 weeks. IBgard was significantly better than placebo in reducing severe or unbearable abdominal pain, abdominal bloating, and sense of incomplete evacuation. IBgard was safe and well tolerated. Severe or Unbearable Intensity Scores of Total and Individual Symptoms - mITT Population
Table # 1: Individual IBS Syndrome of Symptoms Frequency Scores - mITT Population
AGA Abstracts
significant for individual polyols: mannitol (p=0.002), sorbitol (p<0.001), and xylitol (p= 0.014). There was no significant difference in intake of fructose, constituent lipids, total fiber, or total grains between the 2 groups. However, IBS patients consumed significantly more whole grain flour (p=0.028) and whole grain bread (p=0.001) than controls, but similar amounts of refined flour and refined flour bread. Conclusions: IBS-D patients consumed less FODMAPs including lactose and polyols than healthy controls. Whether this is due to IBS patients consciously or unconsciously avoiding foods that trigger their symptoms remains unclear. On the other hand, IBS patients consumed more whole grains. These data suggest that many IBS-D patients alter their dietary FODMAP and grain intake and may prove useful when counseling IBS patients on dietary interventions.
Table 1: Subjects' demographics and healthcare costs
Su1375 Healthcare Cost of Irritable Bowel Syndrome Based on Self-Reported Questionnaires in an Asian Cohort Yu Tien Wang, Andrew Ming Liang Ong, Jing Zeng, Sylvaine Barbier, Bibhas Chakraborty, Van Hai Nguyen
*GLM analysis: p<0.05
Introduction Irritable bowel syndrome (IBS) – a chronic functional disorder that affects 10-20% of the population worldwide – is detrimental to patients' quality of life and imposes substantial healthcare costs. While the extent of IBS's economic burden is well characterized in Western countries, this information is scarce in Asian countries. Aim To characterize healthcare cost from the Asian IBS patient's perspective. Method Self-administered questionnaires were delivered to participants in an IBS public forum in Singapore in august 2014. Diagnosis of IBS was based on subjects' self report of IBS diagnosis by physicians while IBS subtypes were based on ROME III criteria. Healthcare costs were assessed using a validated questionnaire module which interrogates direct and indirect health care costs as well as its sources. Direct costs of IBS include cost of hospitalizations, outpatient medical visits, and non-prescription treatment. Indirect costs include cost of missed work days (assumed to be Singapore dollars S$150/day) and costs associated with days being unable to perform usual duties (assumed to be S$50/day). All costs are presented in US$ using current exchange rate (S$1 = US$0.8). Statistical analysis of costs The average costs were stratified by age, gender, IBS type, and IBS symptom frequency to study their potential differences. The differences in costs between these subgroups were assessed using standard statistical comparison tests (i.e. two sample t-tests and Wilcoxon-Mann-Whitney two-sample tests). A multivariate GLM regression was estimated to identify patient's characteristics that are associated with higher total IBS costs. All statistical analyses were performed using STATA version 13 (Stata Corp, College Station, Texas). Result 256 participants attended the forum and 155 questionnaires were returned. Of these, 92 subjects reported diagnosis of IBS. Among them, 73% were female, 51% were current married and the predominant (88%) ethnic group was Chinese. The subjects' demographics and healthcare costs are presented in table 1. Based on GLM regression analysis, IBS patients have higher health care costs if being male, being married, having IBS symptoms more than once a week and being in the age group of 3544. Conclusion IBS in this cohort of Singaporean patients was associated with significant healthcare costs of around US$2,000 per patient per year. This healthcare burden is large, more than twice the nation's per capita average healthcare expenditure. The majority of the expenses were related to outpatient medical care but there were also significant expenses incurred through non-prescription treatments and indirect costs. Characteristics which predicted higher healthcare costs were male, being married, more frequent symptoms and age between 35-44. Further research is required to identify cost-effective IBS management.
Su1376 Assessment of IBS-D Severity: A Case Study From Two Randomized, DoubleBlind, Placebo-Controlled Pivotal Trials to Evaluate the Efficacy of Oral Ibodutant Jan F. Tack, Simona Scartoni, Giulia Tonini, Kai Schumacher, Monica Bertolotti, Alessandra Nuti, Kerstin Ott, Grazia Simona Cera, Angela Capriati, Carlo A. Maggi Introduction Assessment of the severity of symptoms is fundamental to select Irritable Bowel Syndrome (IBS) patients for inclusion in pivotal trials. In addition to diagnostic Rome III criteria, regulatory guidelines recommend precise severity level for the eligibility of patients (customized by IBS-subtypes), based on scale assessments to be daily recorded by patients during a 2 week run-in period. Severity score of IBS symptoms can also be recorded by the validated IBS-Symptom Severity Score (IBS-SSS) questionnaire. Two ongoing pivotal trials testing ibodutant, a selective and potent antagonist of neurokinin 2 receptors for IBS with Diarrhea (IBS-D), evaluate symptoms severity trough both methods. Aim Evaluation of the correlation between eligibility severity criteria as per regulatory guidelines and severity assessment from IBS-SSS questionnaire. Methods Two double blind, randomized, placebo controlled, Phase III studies are running to evaluate the efficacy and safety of 10 mg oral ibodutant in female patients with IBS-D. After a screening visit, patients undergo a 2-week run-in period (no rescue medication allowed) to confirm all eligibility criteria, including IBS severity based on the severity of abdominal pain (0-10 scale), number of bowel movements and stool consistency, daily recorded through the e-diary questionnaire (e-PRO). IBS severity is also evaluated by IBS-SSS questionnaire (score severity: <175 Mild; >175-300 Moderate; >300 Severe) at the start of run-in (and repeated at the end only for randomized patients). Results Among the 948 female patients who underwent run-in, 665 reported severe IBS symptoms as per IBS-SSS score versus 283 resulting mild/moderate at the start of runin. Based on the 2-week e-PRO results, 612 patients met severity eligibility criteria for randomization, against 336 patients who did not meet them. Table 1 shows that 49.4% of patients resulted to be severe as per IBS-SSS at the start of run-in, and met the eligibility severity criteria as per e-PRO during run-in, whereas 14.7% with mild/moderate IBS-SSS were also not eligible for e-PRO severity. However, a high percentage (35.9%) of patients showed no-concordance between the two methods used. When IBS-SSS was compared only to the severity of pain recorded on e-PRO, the concordance increases to 73%. The concordance between the IBS-SSS questionnaires administered at start and end of the run-in was reported in 82% of randomized patients (Table 2). Conclusion IBS-SSS questionnaire cannot replace e-diary assessment during the 2 week run-in period to determine eligibility of patients to clinical trials as per regulatory requirements for IBS severity. Table 1
*not all the patients resulting eligible for severity were finally randomized and provided a second IBS-SSS (screen failures due to other reason than severity)
AGA Abstracts
S-490