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Su1380 Consistency in Efficacy Outcomes of Eluxadoline-Treated Patients With Irritable Bowel Syndrome With Diarrhea Using Recent and Traditional Endpoints
AGA Abstracts
Su1380
possibility of using autoprobiotic therapy for the prevention of PI-IBS. Materials and methods: The study included 88 patients with verified acute intestinal infections of bacterial etiology. All patients received therapy for the treatment of acute intestinal infections: antibiotics, symptomatic. After treatment the patients were randomized into three groups: the first group of patients (30 persons) received autoprobiotic (autostrains of Enterococcus faecium), the second group (28 persons) probiotic strain Enterococcus faecium L-3, the third (30 persons) - placebo (autoclaved milk). The average age in all groups was comparable. By the studied parameters the groups were comparable. Intestinal microbiocenosis was studied before and within six months treatment by PCR. During the study, the patients kept a diary, in which they noted IBS symptoms daily. Results: It was revealed significant increase of bifidobacteria, enterococcus faecium and reducing the number of conditionally pathogenic enterobacteria in autoprobiotic group patients. After 6 months of follow-up period PI-IBS was diagnosed in 15 of at 68 patients (22.1 %) according to the Rome III criteria. The study shows that PI IBS was revealed significantly less frequent (p=0,0008) in the group of patients who received autoprobiotic (table 1). The incidence of IBS symptoms was significantly less in the group treated with autoprobiotic when compared with the group treated with Enterococcus faecium L-3 (p=0,008) and placebo group (p<0,001). When comparing the incidence of IBS in group 2 and 3, significant differences were not found (p=0,099). Conclusions: Autoprobiotic therapy can significantly improve the intestinal microflora in patients undergoing acute intestinal infection. Autoprobiotic can be successfully used for the prevention of postinfectious IBS. Table 1. The distribution of patients according to the presence of PI-IBS symptoms 6 months after treatment
Consistency in Efficacy Outcomes of Eluxadoline-Treated Patients With Irritable Bowel Syndrome With Diarrhea Using Recent and Traditional Endpoints Marc Zuckerman, Scott Dove, David Andrae, J. Michael Davenport, Lisa Turner, Rocio Lopez, Paul S. Covington Background & Aims: Eluxadoline (ELX), a locally active, mixed mu opioid receptor agonist and delta opioid receptor antagonist, has been shown to improve the symptoms of irritable bowel syndrome with diarrhea (IBS-D) based on a composite endpoint of improvement in stool consistency and reduction in abdominal pain scores. Additional analyses of two Phase 3 clinical trials were conducted to further examine the consistency of efficacy outcomes by comparing the results of the daily composite response endpoint with the patient-friendly, traditional adequate relief (AR) endpoint and with Global Symptom Score (GSS). Methods: Two double-blind, placebo-controlled, Phase 3 clinical trials (3001 and 3002) randomized patients meeting Rome III criteria for IBS-D to twice-daily treatment with ELX (75 or 100 mg) or placebo (PBO). Both trials evaluated efficacy through 26 weeks of treatment. The primary endpoint was composite response (based on simultaneous improvement in daily worst abdominal pain [scale of 0-10] and stool consistency [Bristol Stool Scale 1-7] with ≥50% of days demonstrating a response) evaluated over Weeks 1-12 (with at least 60/84 days of diary compliance) and Weeks 1-26 (with at least 110/182 days of diary compliance). Patients were asked to indicate whether they had AR from their IBS symptoms over the past week (yes/no), and were asked on a daily basis to rate their IBS symptoms over the past 24 hours (0=none; 1=mild; 2=moderate; 3=severe; 4=very severe). Efficacy assessments included Cochran-Mantel-Haenszel (CMH) analysis requiring AR response of ≥6/12 weeks and, for assessment of GSS, CMH analysis of ≥50% of days with either daily GSS <2 or GSS improved by ≥2 compared with the baseline average. Additionally, pooled data using analysis of covariance (ANCOVA) assessed change from baseline (CFB) in GSS. Results: A total of 2428 patients with IBS-D were enrolled across the two trials. Average GSS scores at baseline, Week 12, and Week 26 are presented in Table 1. Table 2 presents responder outcomes for the composite, GSS and AR. More patients (p<0.01) receiving ELX were composite responders compared with patients receiving PBO, especially at ELX 100 mg. Comparable results were seen for AR and GSS endpoints with ELX 75 mg and 100 mg. Efficacy in the ELX 100 mg group was more robust than 75 mg in both trials, and results from Study 3002 were generally more robust than those from Study 3001. Pooled data for ANCOVA CFB for GSS also demonstrated superiority over PBO at Weeks 12 and 26 (p≤0.008). Conclusions: Individual studies and pooled data demonstrated that ELX was superior to PBO in relieving symptoms of IBS-D. Efficacy outcomes for the composite endpoint are consistent with the patient-friendly, traditional AR endpoint, as well as GSS. Additionally, results at 26 weeks were consistent with results at 12 weeks. Table 2. Efficacy outcomes
Su1382 Prevalence of Gastrointestinal Symptoms in Joint Hypermobility Syndrome/ Ehlers-Danlos Syndrome Hypermobility Type Giulia Bolasco, Claudia Celletti, Filippo Camerota, Ivano Biviano, Enrico Corazziari, Danilo Badiali Hypermobility type Ehlers-Danlos syndrome (HT-EDS) is an inherited disorder of connective tissue with heterogeneous clinical manifestations. It was suggested (1) that these patients show an increased prevalence of gastrointestinal disorders, but their relationship with the syndrome has been poorly evaluated. The aim of this study was to assess the prevalence of gastrointestinal manifestations in a HT-EDS population and whether they affect the quality of life. The diagnosis of HT-EDS was established (CF) according with the Villefranche and Brighton criteria. The validated Italian version of Rome III Questionnaire for gastrointestinal symptoms was administered to thirty-eight HT-EDS outpatient women (38,6±11,2yrs) referring to the "Rare Disease Office" of the Policlinico Umberto I, University La Sapienza, Rome and to 35, age matched (40,2±14,4yrs), control women. In addition the EDS-HT patients filled in the SF-36 quality of life questionnaire in relation to intestinal disorders. All patients reported one or more gastrointestinal symptoms. All gastro-intestinal symptoms, except vomiting proctalgia fugax, diarrhea and fecal incontinence, were more frequent in HT-EDS patients than in controls (table 1) and reduced the quality of life (table 2). In conclusion GI symptoms are highly prevalent in EDS patients and contributing largely to symptomatology , affect significantly the quality of life, and aggravate the illness burden, of these patients. (1). Castori M, Camerota F, Celletti C, Danese C, Santilli V, Saraceni VM, Grammatico P. Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients. Am J Med Genet A. 2010a;152A:556-64.
p values based on comparison between each group and placebo. CMH, Cochran-MantelHaenszel Table 1. Average GSS
SD, standard deviation Su1381 Autoprobiotic: Place in the Prevention of Postinfectious Irritable Bowel Syndrome Irina Shumikhina, Zarina Sundukova, Olga Solovyeva, Vladimir Simanenkov Introduction: Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract. About 30% of patients with IBS, have a history of an episode of acute intestinal infection that has allowed to allocate a separate form is a postinfectious irritable bowel syndrome (PI-IBS). Usage of the industrial probiotic strains is associated with a number of problems: elimination of probiotic strains from the host due to immunological incompatibility, which requires long-term administration of high doses of probiotics. All this makes it relevant to explore the possibility of using personalized symbiotic therapy (autoprobiotic), products containing the microbiota of the patient. Objective: To study the
AGA Abstracts
S-492
Su1380
possibility of using autoprobiotic therapy for the prevention of PI-IBS. Materials and methods: The study included 88 patients with verified acute intestinal infections of bacterial etiology. All patients received therapy for the treatment of acute intestinal infections: antibiotics, symptomatic. After treatment the patients were randomized into three groups: the first group of patients (30 persons) received autoprobiotic (autostrains of Enterococcus faecium), the second group (28 persons) probiotic strain Enterococcus faecium L-3, the third (30 persons) - placebo (autoclaved milk). The average age in all groups was comparable. By the studied parameters the groups were comparable. Intestinal microbiocenosis was studied before and within six months treatment by PCR. During the study, the patients kept a diary, in which they noted IBS symptoms daily. Results: It was revealed significant increase of bifidobacteria, enterococcus faecium and reducing the number of conditionally pathogenic enterobacteria in autoprobiotic group patients. After 6 months of follow-up period PI-IBS was diagnosed in 15 of at 68 patients (22.1 %) according to the Rome III criteria. The study shows that PI IBS was revealed significantly less frequent (p=0,0008) in the group of patients who received autoprobiotic (table 1). The incidence of IBS symptoms was significantly less in the group treated with autoprobiotic when compared with the group treated with Enterococcus faecium L-3 (p=0,008) and placebo group (p<0,001). When comparing the incidence of IBS in group 2 and 3, significant differences were not found (p=0,099). Conclusions: Autoprobiotic therapy can significantly improve the intestinal microflora in patients undergoing acute intestinal infection. Autoprobiotic can be successfully used for the prevention of postinfectious IBS. Table 1. The distribution of patients according to the presence of PI-IBS symptoms 6 months after treatment
Consistency in Efficacy Outcomes of Eluxadoline-Treated Patients With Irritable Bowel Syndrome With Diarrhea Using Recent and Traditional Endpoints Marc Zuckerman, Scott Dove, David Andrae, J. Michael Davenport, Lisa Turner, Rocio Lopez, Paul S. Covington Background & Aims: Eluxadoline (ELX), a locally active, mixed mu opioid receptor agonist and delta opioid receptor antagonist, has been shown to improve the symptoms of irritable bowel syndrome with diarrhea (IBS-D) based on a composite endpoint of improvement in stool consistency and reduction in abdominal pain scores. Additional analyses of two Phase 3 clinical trials were conducted to further examine the consistency of efficacy outcomes by comparing the results of the daily composite response endpoint with the patient-friendly, traditional adequate relief (AR) endpoint and with Global Symptom Score (GSS). Methods: Two double-blind, placebo-controlled, Phase 3 clinical trials (3001 and 3002) randomized patients meeting Rome III criteria for IBS-D to twice-daily treatment with ELX (75 or 100 mg) or placebo (PBO). Both trials evaluated efficacy through 26 weeks of treatment. The primary endpoint was composite response (based on simultaneous improvement in daily worst abdominal pain [scale of 0-10] and stool consistency [Bristol Stool Scale 1-7] with ≥50% of days demonstrating a response) evaluated over Weeks 1-12 (with at least 60/84 days of diary compliance) and Weeks 1-26 (with at least 110/182 days of diary compliance). Patients were asked to indicate whether they had AR from their IBS symptoms over the past week (yes/no), and were asked on a daily basis to rate their IBS symptoms over the past 24 hours (0=none; 1=mild; 2=moderate; 3=severe; 4=very severe). Efficacy assessments included Cochran-Mantel-Haenszel (CMH) analysis requiring AR response of ≥6/12 weeks and, for assessment of GSS, CMH analysis of ≥50% of days with either daily GSS <2 or GSS improved by ≥2 compared with the baseline average. Additionally, pooled data using analysis of covariance (ANCOVA) assessed change from baseline (CFB) in GSS. Results: A total of 2428 patients with IBS-D were enrolled across the two trials. Average GSS scores at baseline, Week 12, and Week 26 are presented in Table 1. Table 2 presents responder outcomes for the composite, GSS and AR. More patients (p<0.01) receiving ELX were composite responders compared with patients receiving PBO, especially at ELX 100 mg. Comparable results were seen for AR and GSS endpoints with ELX 75 mg and 100 mg. Efficacy in the ELX 100 mg group was more robust than 75 mg in both trials, and results from Study 3002 were generally more robust than those from Study 3001. Pooled data for ANCOVA CFB for GSS also demonstrated superiority over PBO at Weeks 12 and 26 (p≤0.008). Conclusions: Individual studies and pooled data demonstrated that ELX was superior to PBO in relieving symptoms of IBS-D. Efficacy outcomes for the composite endpoint are consistent with the patient-friendly, traditional AR endpoint, as well as GSS. Additionally, results at 26 weeks were consistent with results at 12 weeks. Table 2. Efficacy outcomes
Su1382 Prevalence of Gastrointestinal Symptoms in Joint Hypermobility Syndrome/ Ehlers-Danlos Syndrome Hypermobility Type Giulia Bolasco, Claudia Celletti, Filippo Camerota, Ivano Biviano, Enrico Corazziari, Danilo Badiali Hypermobility type Ehlers-Danlos syndrome (HT-EDS) is an inherited disorder of connective tissue with heterogeneous clinical manifestations. It was suggested (1) that these patients show an increased prevalence of gastrointestinal disorders, but their relationship with the syndrome has been poorly evaluated. The aim of this study was to assess the prevalence of gastrointestinal manifestations in a HT-EDS population and whether they affect the quality of life. The diagnosis of HT-EDS was established (CF) according with the Villefranche and Brighton criteria. The validated Italian version of Rome III Questionnaire for gastrointestinal symptoms was administered to thirty-eight HT-EDS outpatient women (38,6±11,2yrs) referring to the "Rare Disease Office" of the Policlinico Umberto I, University La Sapienza, Rome and to 35, age matched (40,2±14,4yrs), control women. In addition the EDS-HT patients filled in the SF-36 quality of life questionnaire in relation to intestinal disorders. All patients reported one or more gastrointestinal symptoms. All gastro-intestinal symptoms, except vomiting proctalgia fugax, diarrhea and fecal incontinence, were more frequent in HT-EDS patients than in controls (table 1) and reduced the quality of life (table 2). In conclusion GI symptoms are highly prevalent in EDS patients and contributing largely to symptomatology , affect significantly the quality of life, and aggravate the illness burden, of these patients. (1). Castori M, Camerota F, Celletti C, Danese C, Santilli V, Saraceni VM, Grammatico P. Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients. Am J Med Genet A. 2010a;152A:556-64.
p values based on comparison between each group and placebo. CMH, Cochran-MantelHaenszel Table 1. Average GSS
SD, standard deviation Su1381 Autoprobiotic: Place in the Prevention of Postinfectious Irritable Bowel Syndrome Irina Shumikhina, Zarina Sundukova, Olga Solovyeva, Vladimir Simanenkov Introduction: Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract. About 30% of patients with IBS, have a history of an episode of acute intestinal infection that has allowed to allocate a separate form is a postinfectious irritable bowel syndrome (PI-IBS). Usage of the industrial probiotic strains is associated with a number of problems: elimination of probiotic strains from the host due to immunological incompatibility, which requires long-term administration of high doses of probiotics. All this makes it relevant to explore the possibility of using personalized symbiotic therapy (autoprobiotic), products containing the microbiota of the patient. Objective: To study the
AGA Abstracts
S-492