Reduction in pain: Is it worth the gain? The effect of opioids on the GI tract.

The use of opioid medications for acute and chronic pain has increased significantly in the past 20 years in the United States. Given the high density of opioid receptors in the gastrointestinal tract, side effects are common in these patients including constipation, dysphagia, bloating, nausea, and vomiting. These side effects, which are experienced by most patients who take opioids, can lead to significant impairment in quality of life. Unlike other side effects from opioids, gastrointestinal side effects do not diminish with continued use, often leading patients to reduce or discontinue their opioid treatment to relieve these side effects. Therefore, physicians must be aware and anticipate potential side effects in patients receiving opioids to ensure appropriate pain management.

Emergency department utilisation for inflammatory bowel disease in the United States from 2006 to 2014.

BACKGROUND: Despite advances in treatment, patients with inflammatory bowel disease (IBD) frequently require emergency department (ED) visits and hospitalisations. AIMS: To analyse trends in ED visits and subsequent hospitalisations for IBD in the United States (US). METHODS: Data were analysed from the Nationwide Emergency Department Sample (NEDS) years 2006-2014. The NEDS is the largest all-payer ED database in the US, weighted to represent 135 million visits/year. IBD was identified using ICD-9 codes for Crohn's disease (CD) or ulcerative colitis (UC). Surgeries were identified using procedure codes. RESULTS: The frequency of IBD-ED visits increased 51.8%, from 90 846 visits in 2006 to 137 946 in 2014, which was statistically significant in linear regression. For comparison, all-case ED use between 2006 and 2014 increased 14.8%. In-patient hospitalisations from the ED decreased 12.1% for IBD (from 64.7% rate of hospitalisation from the ED in 2006 to 52.6% in 2014), with a UC:CD ratio of 1.2:1 in 2006 and 1.3:1 in 2014. Chi-square analysis revealed that this was a significant decrease. Surgery rates also showed a statistically significant decrease. The mean ED charge per patient rose 102.5% and the aggregate national cost of IBD-ED visits increased 207.5%. CD accounted for over twice as many visits as UC in both years. UC, age, male gender, highest income quartile, private insurance, Medicaid/Medicare, and tobacco use were associated with in-patient admissions. CONCLUSIONS: The number of ED visits due to IBD and associated charges have continued to rise, while the rates of in-patient hospitalisations referred from the ED and surgeries have decreased.

Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity.

BACKGROUND: Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM: To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. METHODS: Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. RESULTS: Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. CONCLUSIONS: In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. GOV IDENTIFIER: NCT01543178.

Gender differences in chronic constipation on anorectal motility.

BACKGROUND: The epidemiology of chronic constipation (CC) skews toward female predominance, yet men make up an important component of those suffering from CC. We sought to determine whether there are sex-specific differences in symptoms and physiologic parameters on anorectal manometry (ARM). METHODS: We performed a case-control analysis of sequential men and age-matched women (2:1 ratio) presenting for ARM as part of the evaluation of CC. We collected physiologic parameters derived from 3D high-resolution ARM in addition to the ROME III constipation module and the Pelvic Floor Distress Inventory 20 (PFDI-20) questionnaires. We analyzed univariate, sex-specific differences in ARM physiologic parameters and PFDI-20 parameters and adjusted for putative confounders using multivariate logistic regression. KEY RESULTS: Our study enrolled 80 men and 165 age-matched women. Men had a higher median sphincter resting pressure (81.2 vs 75.2 mm Hg, P=.01) and mean squeeze pressure (257.0 vs 170.5 mm Hg, P<.0001) than women. Although men reported significantly less severe straining and incomplete evacuation, they had greater mean rectoanal pressure differential (-106.7 vs -71.1 mm Hg, P<.0001), smaller mean defecation index (0.17 vs 0.27, P=.03) and higher volume threshold for urgency (115.2 v. 103.4 mL, P=.03). However, women were more likely to have abnormal balloon expulsion time (BET) than men (52.7% vs 35.0%, P=.01). After multivariate analysis, male gender was the only independent predictor of a normal BET (OR: 0.48, 95% CI: 0.27-0.86, P=.01). CONCLUSIONS & INFERENCES: Men and women with CC differ with regard to symptom severity and physiologic parameters derived from ARM suggesting differences in their pathophysiology.

Dexamethasone implant in diabetic macular edema in real-life situations.

PURPOSE: To report outcome of eyes with recalcitrant and naive eyes with diabetic macular edema (DME) treated with intravitreal dexamethasone implants (Ozurdex) injection. METHODS: Retrospective multicenter data analysis of eyes with DME treated with Ozurdex implant and with minimum follow-up of at least one year after the first implant. Data collected included demographic details, history of presenting illness, past treatment history, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Paired sample t-test was used to measure mean differences between pre- and post-implant values obtained at baseline and last follow-up. RESULTS: A total of 79 eyes (62 subjects) were included. Sixty-four eyes had been previously treated; 15 eyes were naive. Among the previously treated eyes, mean interval between first Ozurdex injection and any previous treatment was 7.69±8.2 months. In naive eyes, the visual acuity improved from baseline 0.58±0.25 to 0.44±0.33 logMAR at last follow-up (P=0.05). In eyes that had been previously treated, the improvement was from 0.65±0.34 at baseline to 0.48±0.35 logMAR (P=0.01). Mean treatment-free interval was 6.5±4.5 months. Nine eyes were steroid responder with controlled intraocular pressure (IOP), none showed any spike in IOP during the follow-up period. CONCLUSIONS: Ozurdex implant could be a good alternative for recalcitrant as well as naive eyes with DME. The visual gain after initial implant injection was fairly maintained, with additional treatment usually after 6 months in naive eyes. Ozurdex appeared safe even in steroid responders with good control of IOP with antiglaucoma medications.

The clinical predictors of aetiology and complications among 173 patients presenting to the Emergency Department with oesophageal food bolus impaction from 2004-2014.

BACKGROUND: Oesophageal food bolus impaction (OFBI) is a common gastrointestinal emergency. AIM: To describe contemporary aetiologies of OFBI, and variables that may predict eosinophilic esophagitis (EoE) related OFBI as well as complications. METHODS: Patients presenting to the Emergency Department between 2004 and 2014 with OFBI who underwent oesophagogastroduodenoscopy (EGD) were included. Clinical and endoscopic variables, as well as complications, were recorded. Aetiology of OFBI was determined by reviewing endoscopy reports. A diagnosis of EoE was confirmed via pathology (>15 eosinophils/high-powered field) at the index or follow-up EGD. Logistic regression was used to report associations of variables and complications. RESULTS: Of the 173 patients with OFBI, 139 (80%) had an aetiology recognised, the most frequent being EoE (27%, n = 47), Schatzki's ring (20%, n = 34) and oesophageal stricture (13%, n = 22). Six patients (3%) had oesophageal cancer. Patients with EoE-related OFBI tended to be younger (42 vs. 69 years, P < 0.001), male (81% vs. 52%, P = 0.001), have a prior history of OFBI (45% vs. 18%, P = 0.001), and present during spring or summer (62% vs. 44%, P = 0.04). Eighteen patients (10%) had a complication associated with OFBI, with 3 (2%) perforations. On multivariate regression, patients with EoE-related OFBI were not more likely to have a complication (OR 1.07, P = 0.92), although hypoxia at presentation (OR 59.7, P = 0.006) was associated with complications. CONCLUSIONS: Eosinophilic esophagitis accounts for over a quarter of patients with oesophageal food bolus impaction. Overall complication rate was 10%, with a 2% perforation rate. Clinical characteristics of patients with eosinophilic esophagitis differ from other patients with oesophageal food bolus impaction.

Inpatient burden of childhood functional GI disorders in the USA: an analysis of national trends in the USA from 1997 to 2009.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are among the most common outpatient diagnoses in pediatric primary care and gastroenterology. There is limited data on the inpatient burden of childhood FGIDs in the USA. The aim of this study was to evaluate the inpatient admission rate, length of stay (LoS), and associated costs related to FGIDs from 1997 to 2009. METHODS: We analyzed the Kids' Inpatient Sample Database (KID) for all subjects in which constipation (ICD-9 codes: 564.0-564.09), abdominal pain (ICD-9 codes: 789.0-789.09), irritable bowel syndrome (IBS) (ICD-9 code: 564.1), abdominal migraine (ICD-9 code: 346.80 and 346.81) dyspepsia (ICD-9 code: 536.8), or fecal incontinence (ICD-codes: 787.6-787.63) was the primary discharge diagnosis from 1997 to 2009. The KID is the largest publicly available all-payer inpatient database in the USA, containing data from 2 to 3 million pediatric hospital stays yearly. KEY RESULTS: From 1997 to 2009, the number of discharges with a FGID primary diagnosis increased slightly from 6,348,537 to 6,393,803. The total mean cost per discharge increased significantly from $6115 to $18,058 despite the LoS remaining relatively stable. Constipation and abdominal pain were the most common FGID discharge diagnoses. Abdominal pain and abdominal migraine discharges were most frequent in the 10-14 year age group. Constipation and fecal incontinence discharges were most frequent in the 5-9 year age group. IBS discharge was most common for the 15-17 year age group. CONCLUSIONS & INFERENCES: Hospitalizations and associated costs in childhood FGIDs have increased in number and cost in the USA from 1997 to 2009. Further studies to determine optimal methods to avoid unnecessary hospitalizations and potentially harmful diagnostic testing are indicated.

The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials.

BACKGROUND: Few clinical trials in chronic idiopathic constipation (CIC) patients have evaluated abdominal symptom severity and whether CIC patients with abdominal symptoms respond similarly to patients with limited abdominal symptoms. AIMS: To examine abdominal symptom severity and relationships between symptoms and global measures at baseline; compare linaclotide's effect on symptoms in subpopulations with more or less abdominal pain; and assess relationships between symptom improvement and global measures in these two subpopulations. METHODS: In two phase 3 trials, patients meeting modified Rome II CIC criteria were assigned to linaclotide 145 µg, 290 µg, or placebo once daily. Patients rated abdominal and bowel symptoms daily during 2-week pre-treatment and 12-week treatment periods. Linaclotide's effect on symptoms and global measures [constipation severity, health-related quality of life (HRQOL), treatment satisfaction] and their inter-relationships were assessed in post hoc analyses of abdominal pain subpopulations. RESULTS: Of 1271 CIC patients, 23%, 32%, and 43% reported moderate-to-severe abdominal pain, discomfort, and bloating, respectively, during baseline. In more-severe abdominal pain patients, abdominal symptoms were more strongly correlated than bowel symptoms with global measures, but in less-severe abdominal pain patients, abdominal and bowel symptoms were similarly correlated with global measures, at baseline and post-treatment. Linaclotide significantly improved all symptoms and global measures in both subpopulations. CONCLUSIONS: When abdominal pain is present in CIC, abdominal and not bowel symptoms may drive patient assessments of constipation severity, HRQOL, and treatment satisfaction. Linaclotide (145 µg and 290 µg) is an effective treatment for both abdominal and bowel symptoms, even in CIC patients with more severe abdominal pain at baseline. (Clinicaltrials.gov: NCT00765882, NCT00730015).

Qualitative development of a patient-reported outcome symptom measure in diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Despite a documented clinical need, no patient reported outcome (PRO) symptom measure meeting current regulatory requirements for clinically relevant end points is available for the evaluation of treatment benefit in diarrhea-predominant IBS (IBS-D). METHODS: Patients (N=113) with IBS-D participated in five study phases: (1) eight concept elicitation focus groups (N=34), from which a 17-item IBS-D Daily Symptom Diary and four-item IBS-D Symptom Event Log (Diary and Event Log) were developed; (2) one-on-one cognitive interviews (N=11) to assess the instrument's comprehensiveness, understandability, appropriateness, and readability; (3) four data triangulation focus groups (N=32) to confirm the concepts elicited; (4) two hybrid (concept elicitation and cognitive interview) focus groups (N=16); and (5) two iterative sets of one-on-one cognitive interviews (N=20) to further clarify the symptoms of IBS-D and debrief a revised seven-item Diary and four-item Event Log. RESULTS: Of thirty-six concepts initially identified, 22 were excluded because they were not saturated, not clinically relevant, not critical symptoms of IBS-D, considered upper GI symptoms, or too broad or vaguely defined. The remaining concepts were diarrhea, immediate need (urgency), bloating/pressure, frequency of bowel movements, cramps, abdominal/stomach pain, gas, completely emptied bowels/incomplete evacuation, accidents, bubbling in intestines (bowel sounds), rectal burning, stool consistency, rectal spasm, and pain while wiping. The final instrument included a daily diary with separate items for abdominal and stomach pain and an event log with four items completed after each bowel movement as follows: (1) a record of the bowel movement/event and an assessment of (2) severity of immediacy of need/bowel urgency, (3) incomplete evacuation, and (4) stool consistency (evaluated using the newly developed Astellas Stool Form Scale). Based on rounds of interviews and clinical input, items considered secondary or nonspecific to IBS-D (rectal burning, bubbling in intestines, spasms, and pain while wiping) were excluded. CONCLUSIONS: The IBS-D Symptom Diary and Event Log represent a rigorously developed PRO instrument for the measurement of the IBS-D symptom experience from the perspective of the patient. Its content validity has been supported, and future work should evaluate the instrument's psychometric properties.

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials.

BACKGROUND: The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non-constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking. AIM: To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials. METHODS: A post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively. RESULTS: Patients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths. CONCLUSIONS: The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non-constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

BACKGROUND: US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. METHODS: Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. KEY RESULTS: 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. CONCLUSIONS & INFERENCES: Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies.

Irritable bowel syndrome subtypes: constipation, diarrhea and mixed bowel pattern: tertium datur.

The study by Su et al. published in this issue of NGM provides helpful insight into a relatively large, yet understudied, subgroup of IBS known as IBS with mixed bowel pattern (IBS-M). These investigators found among their 289 IBS subjects who underwent detailed assessment the IBS-M subtype to be particularly common. Interestingly, prior use of laxatives or antidiarrheal agents was found to potentially explain the mixed bowel pattern in approximately 30% of patients. These IBS-M patients tended to report more severe IBS symptoms. IBS-M patients had bowel symptoms more similar to IBS-D than IBS-C, particularly with regard to the rectal urgency. Hopefully many more studies will be forthcoming to further our understanding of IBS-M.

In-patient discharge rates for the irritable bowel syndrome - an analysis of national trends in the United States from 1997 to 2010.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common out-patient diagnoses in primary care and gastroenterology. There are limited data on the rate and costs associated with in-patient discharges for IBS. AIM: To estimate the incidence and costs of hospital discharges for IBS in the United States. METHODS: We analysed the National Inpatient Sample database for all subjects in which IBS (ICD-9 code: 564.1) was the principal discharge diagnosis from 1997 to 2010. The National Inpatient Sample contains data from approximately 8 million hospital stays each year. Our findings reflected patient and hospital characteristics like geographical region and bed size. RESULTS: In 1997, there were 11 433 patients with a principal discharge diagnosis of IBS as compared to 12 842 in 2010 (P > 0.9, GoF test). The mean length of stay for IBS also remained the same between 1997 and 2010 at 3.7 ± 0.1 days. However, during this period, the mean hospital charges per hospitalization increased by 207.8% from $6873 ± 198 in 1997 to $21 153 ± 598 in 2010 (P < 0.01). The aggregate charges (i.e., 'national bill') for IBS increased by 245.5% from $78 524 129 ± 3 781 316 in 1997 to $271 311 405 ± 14 023 289 in 2010 (P < 0.01). CONCLUSIONS: The number of in-patient discharges and length of stay for IBS have remained relatively stable between 1997 and 2010, whereas the cost associated with these discharges has increased significantly. In-patient costs associated with IBS contribute significantly to the total healthcare bill. Further research on the cost-effectiveness of diagnostic procedures and therapies in IBS is required.

Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis.

BACKGROUND: TZP-102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a. METHODS: Patients with type 1 or 2 diabetes, delayed gastric half-emptying (T(1/2)), and ≥3 months gastroparesis symptoms randomized 1 : 1 : 1 to double-blind placebo, 10-mg, or 20-mg TZP-102 once daily for 12 weeks (Study TZP-102-CL-G003). Study TZP-102-CL-G004 patients randomized 1 : 1 to 10-mg TZP-102:placebo three-times-daily. Primary endpoint was change-from-baseline through Weeks 11-12 in Daily Diary of Gastroparesis Symptoms Questionnaire (GSDD) via electronic Patient Recorded Outcome device: worst severity of nausea, early satiety, bloating, and upper abdominal pain in 24 h (0 = none-to-5 = very severe). GSDD Composite Score for eligibility was ≥2.5 (Day-14-to-baseline). Patient Overall Treatment Evaluation (OTE) provided an anchor-based minimal clinically important difference (MCID) for GSDD Composite Score. KEY RESULTS: Study TZP-102-CL-G003 enrolled 201 outpatients: females 72%; Caucasians 87%; type 2 diabetes 61%; insulin-dependent 65%; age mean ± SD 53 ± 11.3 years; HbA1c 7.8 ± 1.5%; GCSI 3.4 ± 0.7; GSDD Composite 3.6 ± 0.6; gastric T1/2 131 ± 32 min; n = 69 (10-mg), n = 66 (20-mg), n = 66 (placebo). Primary endpoint (GSDD): significant improvement in all arms, although not for TZP-102 vs placebo: mean change-from-baseline -1.7, -1.4, -1.5 (10-mg, 20-mg, placebo); Gastroparesis Cardinal Symptom Index -1.8, -1.6, -1.5, respectively. The OTE (all patients) at Week-12 was: Patient 3.7 ± 3.2 and Physician 3.6 ± 3.0 with median score for both of 5.0 = important on scale of improvement; individual MCID was 1.61 and 0.94 for group analyses, greater than expected. Study TZP-102-CL-G004 with similar demographic/disease characteristics was prematurely terminated for efficacy futility (n = 64 with Week-4 assessments). CONCLUSIONS & INFERENCES: Efficacy of TZP-102 was not demonstrated compared with placebo in diabetic gastroparesis; however, there was substantial symptom improvement in all arms (ClinicalTrials.gov NCT01452815/NCT01664637).

An evaluation of the FDA responder endpoint for IBS-C clinical trials: analysis of data from linaclotide Phase 3 clinical trials.

BACKGROUND: Our objective was to evaluate the performance of the Food and Drug Administration (FDA) Responder Endpoint for clinical trials in IBS-C, using data from two large Phase 3 clinical trials of linaclotide. The FDA interim endpoint requires that, for 50% of trial weeks, patients report ≥30% decrease in Abdominal Pain at its worst and (in the same week) an increase in Complete Spontaneous Bowel Movements (CSBMs) of ≥1 from baseline. METHODS: Anchor-based methodology was used to estimate thresholds of clinically meaningful change using symptom-specific patient rating of change questions (PRCQs) and symptom severity questions. The diagnostic accuracy of the FDA Responder Endpoint was assessed using sensitivity/specificity-based methods. KEY RESULTS: Using anchor-based methods, the estimates of the clinically meaningful improvement thresholds for Abdominal Pain ranged from 25.9% to 32.4% and thresholds for increase in weekly CSBM rate ranged from 1.4 to 1.6 CSBMs per week. Compared with the symptom-specific PRCQs for patient rating of relief, the FDA Responder Endpoint has a sensitivity of 60.7%, a specificity of 93.5%, and an accuracy of 82.0%. Changing the number of weeks required to be a responder or the percentage improvement in the Abdominal Pain criteria did not result in notable improvement in the accuracy of the FDA Responder Endpoint. CONCLUSIONS & INFERENCES: The FDA Responder Endpoint for IBS-C clinical trials represents clinically meaningful improvements in IBS-C symptoms for patients with excellent specificity and reasonable sensitivity.