Baseline Abdominal Pain Research Articles

Factors Associated With Adherence to a Low Fermentable Carbohydrate Diet in Children With Functional Gastrointestinal Disorders

BackgroundThe low–fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD) has been associated with reduced symptomology in pediatric functional gastrointestinal disorders (FGIDs). The LFD is a complex dietary intervention that may be difficult to follow; thus, there is great interest in determining factors that contribute to adherence. ObjectiveTo examine whether baseline abdominal pain, emotional/behavioral problems, or quality of life predict adherence to the LFD in children with FGIDs. DesignThis was a single-group pre–post intervention design within a larger randomized controlled trial. Participants/settingThirty 7- to 12-year-old children with FGIDs were recruited from pediatric gastrointestinal and primary care settings throughout Texas from 2019 to 2021. Evaluated participants were randomized to an LFD intervention as part of a larger randomized controlled trial. InterventionParticipants received dietary counseling and followed the LFD for 3 weeks. MeasuresEmotional or behavioral problems and quality of life were obtained via parent report, and abdominal pain was measured via child report. Adherence was assessed by using diet records and computed by a decrease in consumption of overall FODMAP intake. Statistical analyses performedA hierarchical generalized linear mixed regression model examined factors associated with adherence. ResultsGreater baseline quality of life was associated with better adherence to the LFD (beta coefficient β = −.02, P = 0.03), and baseline emotional/behavioral problems and abdominal pain complaints were not significantly associated with adherence (all Ps > 0.28). ConclusionsHigher child quality of life as reported by parents was related to increased adherence to this complex dietary intervention.

Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study

BackgroundRifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.MethodsThis was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman’s rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant.ResultsOf the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022).ConclusionThe eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.

A185 SUSTAINED SYMPTOM CONTROL WITH MIRIKIZUMAB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS IN THE LUCENT-2 MAINTENANCE TRIAL

A185 SUSTAINED SYMPTOM CONTROL WITH MIRIKIZUMAB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS IN THE LUCENT-2 MAINTENANCE TRIAL

Accumulation of health complaints is associated with persistent musculoskeletal pain two years later in adolescents: The Fit Futures study.

There is limited knowledge on the association between different health complaints and the development of persistent musculoskeletal pain in adolescents. The aims of this study were to assess whether specific health complaints, and an accumulation of health complaints, in the first year of upper-secondary school, were associated with persistent musculoskeletal pain 2 years later. We used data from a population-based cohort study (the Fit Futures Study in Norway), including 551 adolescents without persistent musculoskeletal pain at baseline. The outcome was persistent musculoskeletal pain (≥3 months) 2 years after inclusion. The following self-reported health complaints were investigated as individual exposures at baseline: asthma, allergic rhinitis, atopic eczema, headache, abdominal pain and psychological distress. We also investigated the association between the accumulated number of self-reported health complaints and persistent musculoskeletal pain 2 years later. Logistic regression analyses estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs). At the 2-year follow-up, 13.8% (95% CI [11.2-16.9]) reported persistent musculoskeletal pain. Baseline abdominal pain was associated with persistent musculoskeletal pain 2 years later (OR 2.33, 95% CI [1.29-4.19], p = 0.01). Our analyses showed no statistically significant associations between asthma, allergic rhinitis, atopic eczema, headache or psychological distress and persistent musculoskeletal pain at the 2-year follow-up. For the accumulated number of health complaints, a higher odds of persistent musculoskeletal pain at the 2-year follow-up was observed for each additional health complaint at baseline (OR 1.33, 95% CI [1.07-1.66], p = 0.01). Health care providers might need to take preventive actions in adolescents with abdominal pain and in adolescents with an accumulation of health complaints to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in adolescents.

S524 Predictors of Placebo Response in Patients With Irritable Bowel Syndrome and Constipation: A Post-Hoc Analysis From Pooled Phase 2b/3 Studies Assessing the Safety and Efficacy of Linaclotide

Introduction: In clinical studies of irritable bowel syndrome (IBS), the placebo response rate is variable, with a pooled placebo response rate of 34% for the US Food and Drug Administration (FDA) abdominal pain responder endpoint.1 Further understanding of the factors that drive the placebo response can improve clinical study design. We aim to identify potential factors associated with a high placebo response via a post-hoc analysis of clinical studies in IBS patients with constipation (IBS-C). Methods: Patient data from placebo-controlled studies that assessed the efficacy and safety of linaclotide for IBS-C were pooled from 1 phase 2b (NCT02559206) and 3 phase 3 (NCT00948818, NCT00938717, NCT03573908) studies. Inclusion criteria were similar across studies, and all patients had a baseline abdominal pain severity score ≥3 (0–10 scale). The primary endpoint of interest was abdominal pain responder, defined as ≥30% improvement from a 2-week baseline in average daily worst abdominal pain score for ≥50% of the first 12 weeks on treatment. Predictors of placebo response were identified using backwards selection via a regression analysis from a list of demographics and baseline disease characteristics. Additionally, standardized coefficients were calculated to rank the magnitude of association of each selected predictor with the response. Results: The 4 studies included 2073 patients (1027 placebo and 1046 linaclotide 290 μg). Two predictors of placebo response were identified as having the largest impact on the FDA abdominal pain responder endpoint. Higher baseline variation in abdominal pain was associated with higher placebo response (coefficient, standard error [SE]: 0.20, 0.068; P = .0032), and higher mean baseline abdominal pain was associated with lower placebo response (coefficient, SE: −0.15, 0.019; P < .0001) [Table]. Age, sex, baseline spontaneous bowel movement frequency, baseline Bristol Stool Form Scale score, anxiety, depression, and prior gastrointestinal drugs taken were not found to impact the placebo response for the abdominal pain responder endpoint. Conclusion: In this pooled analysis of IBS-C clinical studies, higher baseline variation in abdominal pain was a positive predictor of placebo response, while higher mean baseline abdominal pain score was a negative predictor of placebo response. These findings may have implications towards future clinical study design. Table 1. - Factors that predict placebo response for abdominal pain improvement, pooled data from phase 2b/3 studies Predictor Placebo (n = 1046) Estimated coefficient (SE) P value SC SD of baseline abdominal pain 0.20 (0.068) .0032 0.08 Mean baseline pain −0.15 (0.019) < .0001 −0.14 A responder was defined as ≥30% improvement in average daily worst abdominal pain score from baseline for 50% of weeks on treatment. Predictors assessed were age, sex, baseline spontaneous bowel movement, mean baseline abdominal pain score, SD of baseline abdominal pain score, pre-US Food and Drug Administration approval, baseline Bristol Stool Form Scale score, anxiety, depression, baseline pain conditions, prior gastrointestinal drug taken. SC, standardized coefficient; SD, standard deviation; SE, standard error.

S532 Plecanatide Improves Severe Abdominal Pain and Severe Bloating in Individuals With Irritable Bowel Syndrome With Constipation (IBS-C): A Pooled Analysis of Two Phase 3 Trials

Introduction: IBS-C is a disorder of gut-brain interaction characterized by abdominal pain related to defecation and hard stool consistency. Bloating is also amongst the most common symptoms. Plecanatide is indicated in the United States for the treatment of IBS-C in adults. The aim of this study was to evaluate the efficacy of plecanatide for severe abdominal pain and/or severe bloating in patients with IBS-C. Methods: Data were pooled and analyzed post hoc from two phase 3, randomized trials of adults with IBS-C treated with plecanatide 3 mg (FDA-approved dose) or placebo once daily for 12 weeks (NCT02387359; NCT02493452). Patients rated abdominal pain and bloating severity separately using an 11-point scale (0 [none] to 10 [worst possible]). A subgroup analysis was conducted in patients with severe pain, severe bloating, or both at baseline. Symptom scores ≥ 8 were defined as severe. Response was defined as a ≥ 30% improvement from baseline in symptom score(s) at Week 12. A correlation analysis measured the strength of associations between abdominal pain and bloating. A coefficient (r) value of > 0.90-1.00 was considered very strong positive correlation; > 0.70-0.90, strong positive correlation. Results: At baseline, 285 (19.6%) of 1453 patients reported severe abdominal pain, 311 (21.4%) reported severe bloating, and 233 (16.0%) reported both symptoms as severe. A significantly greater percentage of plecanatide-treated patients with severe baseline abdominal pain were responders vs placebo at Week 12 (Δ=14.6%, P=0.01 [Figure]). In addition, a significantly greater percentage of plecanatide-treated patients with severe baseline bloating treated were responders vs placebo at Week 12 (Δ=14.9%; P=0.005 [Figure]). In patients with both symptoms rated severe at baseline, a numeric difference favored plecanatide vs placebo (Δ=12.9%; P=0.05 [Figure]). In the overall and severe pain/bloating patient subgroups, changes from baseline to Week 12 in abdominal pain and bloating were strongly correlated to each other (overall population: r=0.85-0.88; both severe subgroup, r=0.92-0.95; Table). Conclusion: In patients with IBS-C and severe abdominal pain and/or severe bloating, plecanatide treatment reduced symptom severity vs placebo, with strong correlations in symptom responses. This suggests a parallel pathogenesis and associated generalized improvement in the visceral hypersensitivity underlying these symptomsFigure 1.: Percentage of Patients With ≥ 30% Improvement From Baseline in Severe Abdominal Pain, Bloating, or Both at Week 12, by Subgroup Table 1. - Correlation of Change From Baseline at Week 12 in Abdominal Pain and Bloating Symptoms in Overall Population and Those With Severe Baseline Abdominal Pain and Bloating Population Abdominal pain and bloating Spearman correlation coefficient, r Pearson correlation coefficient, r Overall population 0.85* 0.88* Severe abdominal pain and bloating population 0.92* 0.95* *P < 0.001 .

Predictors of Successful Yttrium-90 Radioembolization Bridging or Downstaging in Patients with Hepatocellular Carcinoma.

Purpose This study aims to identify clinical and imaging prognosticators associated with the successful bridging or downstaging to liver transplantation (LT) in patients undergoing Yttrium-90 radioembolization (Y90-RE) for hepatocellular carcinoma (HCC). Methods Retrospectively, patients with Y90-RE naïve HCC who were candidates or potential candidates for LT and underwent Y90-RE were included. Patients were then divided into favorable (maintained or achieved Milan criteria (MC) eligibility) or unfavorable (lost eligibility or unchanged MC ineligibility) cohorts based on changes to their MC eligibility after Y90-RE. Penalized logistic regression analysis was performed to identify the significant baseline prognosticators. Results Between 2013 and 2018, 135 patients underwent Y90-RE treatment. Among the 59 (42%) patients within MC, LT eligibility was maintained in 49 (83%) and lost in 10 (17%) patients. Within the 76 (56%) patients outside MC, eligibility was achieved in 32 (42%) and unchanged in 44 (58%). Among the 81 (60%) patients with a favorable response, 16 (20%) went on to receive LT. Analysis of the baseline characteristics revealed that lower Albumin-Bilirubin score, lower Child–Pugh class, lower Barcelona Clinic Liver Cancer stage, HCC diagnosis using dynamic contrast-enhanced imaging on CT or MRI, normal/higher albumin levels, decreased severity of tumor burden, left lobe HCC disease, and absence of HBV-associated cirrhosis, baseline abdominal pain, or fatigue were all associated with a higher likelihood of bridging or downstaging to LT eligibility (p's < 0.05). Conclusion Certain baseline clinical and tumor characteristics are associated with the successful bridging or downstaging of potential LT candidates with HCC undergoing Y90-RE.

S0026 Predictors for Improvement of Chronic Pancreatitis Symptoms After Single Operator Pancreatoscopy With Intraductal Lithotripsy or Extracorporeal Shock Wave Lithotripsy for Large Main Pancreatic Duct Stones

INTRODUCTION: Main pancreatic ductal stones (MPDS) complicate chronic pancreatitis (CP), leading to disabling symptoms such as intractable pain and exocrine pancreatic insufficiency (EPI). Large MPDS (≥5 mm) are more difficult to extract and require lithotripsy with either single operator pancreatoscopy with intraductal lithotripsy (SOPIL) or extracorporeal shock wave lithotripsy (ESWL). This study aims to identify clinical predictors for improvement of CP symptoms after MPDS lithotripsy. METHODS: We retrospectively identified CP patients from 9/2013 to 9/2019 who underwent SOPIL or ESWL for MPDS therapy at our center. Electrohydraulic lithotripsy (EHL) was used for SOPIL. Successful stone clearance was defined as >80% stone fragmentation and extraction. Clinical outcomes: patient reported pain improvement at follow-up, improvement of EPI defined by cessation of enzyme supplementation. Possible predictors identified in univariate logistic regression models (P-value < 0.25) were subsequently used in multivariable logistic regression models, with significance defined as P-value < 0.05. RESULTS: Of the 217 MPDS patients managed with lithotripsy, technical success occurred in 189/217 (87.1%). Pain improvement occurred in 168/197 (85.3%). Exocrine insufficiency was present in 109 and pancreas enzyme supplementation was able to be discontinued in 8 (7.3%) after stone clearance. Analysis for predictors of pain improvement (Table 1) identified concurrent exocrine insufficiency, alcohol etiology, idiopathic etiology, and technically successful stone clearance as possible predictors. On multivariable analysis, technical success was highly predictive of pain improvement (OR 196.57 [41.322–935.10], P < 0.001). Analysis for predictors of EPI improvement identified multiple possible predictors (Table 2). On multivariable analysis, a SOPIL approach (OR 43.565 [3.146–603.34], P = 0.005) predicted EPI improvement and upstream PD diameter increase by every 1 mm was a negative predictor for EPI improvement (OR 0.512 [0.284–0.925], P = 0.026).Table 1.: Univariate and multivariable logistic regression model assessing predictors of pain improvement in patients who underwent single operator pancreatoscopy with intraductal lithotripsy (SOPIL) or extracorporeal shock wave lithotripsy (ESWL).Table 2.: Univariate and multivariable logistic regression model assessing predictors of exocrine pancreatic insufficiency improvement (defined by cessation of pancreatic enzymes supplementation) in patients who underwent single operator pancreatoscopy with intraductal lithotripsy (SOPIL) or extracorporeal shock wave lithotripsy (ESWL). CONCLUSION: Technical success of lithotripsy for MPDS predicted improvement of baseline abdominal pain in CP independent of other clinical factors. A SOPIL over ESWL approach independently predicted improvement of EPI symptoms. Upstream main pancreatic duct diameter as a possible surrogate marker for duration of obstruction and organ atrophy is a negative predictor for resolution of EPI symptoms after lithotripsy approaches for MPDS.

Associations of Abdominal Pain and Psychosocial Distress Measures With Health-Related Quality-of-Life in Pediatric Healthy Controls and Irritable Bowel Syndrome.

Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear. The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS. Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of abdominal pain and psychosocial distress with HRQOL. Eight-five HC and 213 children with IBS participated. Somatization was most strongly associated with Physical HRQOL in HC, and functional disability was most strongly related in IBS. With respect to Psychosocial HRQOL, somatization was most strongly associated for both HC and IBS; depression was also significantly associated in HC. The strength of association between somatization and Physical HRQOL differed between groups; the negative association was less pronounced for IBS than HC. The association between functional disability and both Physical and Psychosocial HRQOL differed significantly between groups; the negative associations were more pronounced for IBS than HC. Multiple psychosocial distress measures, including somatization, were associated with HRQOL in children with IBS; HRQOL in HC was driven consistently by somatization, to the exclusion of other psychosocial concerns. The associations of somatization and functional disability with HRQOL are distinctly different between HC and IBS. This knowledge supports utilization of psychosocial interventions to improve overall well-being for children with IBS.

Predictors of Survival after Yttrium-90 Radioembolization of Chemotherapy-Refractory Hepatic Metastases from Breast Cancer

PurposeTo determine predictors of survival after transarterial radioembolization of hepatic metastases from breast cancer. Materials and MethodsTwenty-four patients with chemotherapy-refractory hepatic metastases from breast cancer who underwent radioembolization from 2013 to 2018 were evaluated based on various demographic and clinical factors before and after treatment. Overall survival (OS) was estimated by Kaplan–Meier method. Log-rank analysis was performed to determine predictors of prolonged OS from the time of first radioembolization and first hepatic metastasis diagnosis. ResultsMedian OS times were 35.4 and 48.6 months from first radioembolization and time of hepatic metastasis diagnosis, respectively. Radioembolization within 6 months of hepatic metastasis diagnosis was a positive predictor of survival from first radioembolization, with median OS of 38.9 months vs 22.1 months for others (P = .033). Estrogen receptor (ER)–positive status predicted prolonged survival (38.6 months for ER+ vs 5.4 months for ER−; P = .005). The presence of abdominal pain predicted poor median OS: 12.8 months vs 38.6 months for others (P < .001). The presence of ascites was also a negative predictor of OS (1.7 months vs 35.4 months for others; P = .037), as was treatment-related grade ≥ 2 toxicity at 3 months (5.4 months vs 38.6 months for others; P = .017). ConclusionsIn patients with metastatic breast cancer, radioembolization within 6 months of hepatic metastasis diagnosis and ER+ status appear to be positive predictors of prolonged survival. Conversely, baseline abdominal pain, baseline ascites, and treatment-related grade ≥ 2 toxicity at 3 months after treatment appear to be negative predictors of OS.

RETRACTED: Gluten Does Not Induce Gastrointestinal Symptoms in Healthy Volunteers: A Double-Blind Randomized Placebo Trial

RETRACTED: Gluten Does Not Induce Gastrointestinal Symptoms in Healthy Volunteers: A Double-Blind Randomized Placebo Trial

Characterization of Abdominal Pain Response to Rifaximin in Patients with Irritable Bowel Syndrome with Diarrhea (IBS-D), by Baseline Pain Severity: Presidential Poster Award

Introduction: Rifaximin is indicated for the treatment of IBS-D in adults. This post hoc analysis of a phase 3 trial evaluated response to 2 courses of rifaximin in patients subgrouped by baseline abdominal pain severity. Methods: Adults with IBS-D (mean daily abdominal pain score ≥3) received a 2-week course of rifaximin 550 mg three times daily. Abdominal pain was assessed daily (score range, 0-10). Patients who responded (during 4-week evaluation period) and then had symptom recurrence during an additional ≤ 18-week observation period (up to 22 weeks post-treatment) received a second 2-week rifaximin course and response was assessed during a 4-week evaluation period. Response was defined as a ≥30% decrease from baseline in mean weekly abdominal pain score and ≥50% decrease from baseline in days/week with Bristol Stool Scale type 6/7 (mushy/watery) stool (composite endpoint) for ≥2 of the first 4 weeks post-treatment. Subgroups were defined by baseline abdominal pain scores of <5.0 (group A), ≥5.0 to <8.0 (group B), and ≥8.0 (group C). Results: 2579 patients received the first rifaximin course (68.2% female; mean age, 46.4 y; mean baseline abdominal pain score, 5.5 [median, 5.4]). In 2438 patients evaluable for efficacy (group A, n=962; group B, n=1260; group C, n=216), response to rifaximin (composite endpoint) was observed in 40.4%, 47.0%, and 43.1% of patients in groups A, B, and C, respectively. Response for the individual abdominal pain component was observed in 57.0%, 57.9%, and 49.5% of patients, respectively. In 328 patients who experienced symptom recurrence and received repeat treatment with rifaximin (group A, n=114; group B, n=178; group C, n=36), median baseline abdominal pain score at repeat treatment baseline was 4.4 (mean, 4.6), lower than observed at first-course baseline. When subgrouped by repeat treatment baseline pain score, response to repeat rifaximin treatment (composite endpoint) was reported in 38.6%, 34.8%, and 27.8% of patients in groups A, B, and C, respectively. Response for abdominal pain component was reported by 57.9%, 50.6%, and 50.0% of patients, respectively. Conclusion: In adults with IBS-D treated with rifaximin, a high percentage of patients had clinically meaningful improvement in abdominal pain irrespective of baseline abdominal pain severity category and treatment course (first vs repeat treatment). These data support rifaximin efficacy in improving IBS-related abdominal pain symptoms.

Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome

Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. We performed a double-blind placebo-controlled (maltodextrin) cross-over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1-week pain and stool diaries and a 3-day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. Subjects had more mean episodes of abdominal pain/day during the fructan-containing diet (3.4 ± 2.6) vs the maltodextrin-containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P= .01). Hydrogen (but not methane) production was greater while subjects were on the fructan-containing diet (617 ± 305 ppm∗h) than the maltodextrin-containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan-containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan-sensitive and fructan-insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.

Impact of Baseline Pain Severity on the Efficacy of Eluxadoline in Patients with Irritable Bowel Syndrome with Diarrhea

Introduction: Eluxadoline, a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist that is locally active in the gastrointestinal tract, is approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. In two Phase 3 studies, eluxadoline significantly improved symptoms of IBS-D based on a composite endpoint of simultaneous improvement in stool consistency and abdominal pain scores. Post hoc analyses of pooled data from these trials were conducted to further evaluate the impact of baseline abdominal pain severity on treatment outcomes. Methods: Two double-blind, placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients meeting Rome III criteria for IBS-D to twice daily treatment with eluxadoline 75 or 100 mg or placebo. Patients rated IBS symptoms daily, including worst abdominal pain (WAP, 0-10 scale) and stool consistency (Bristol Stool Scale [BSS]). The primary efficacy endpoint was composite response, based on simultaneous daily improvement of ≥30% in WAP score vs. baseline and BSS score < 5 with ≥50% of days demonstrating a response, evaluated over 12 and 26 weeks. The Irritable Bowel Syndrome Quality of Life instrument was assessed at baseline, Week 4, and each subsequent visit. Pooled data were stratified by baseline abdominal pain score ( < 5; 5-< 8; ≥8) and composite, abdominal pain, and stool consistency responder rates over Weeks 1-12 and 1-26 were calculated. Statistical inferences were not made due to this being a post hoc analysis and the small sample size of patients with baseline abdominal pain score ≥8.Table 1Results: 2428 IBS-D patients were enrolled across both trials. Proportions of composite, abdominal pain, and stool consistency responders with eluxadoline were greater than with placebo in the overall population and in all baseline abdominal pain severity subgroups over Weeks 1-12 and 1-26 (Table). Responder rates for composite, stool consistency, and abdominal pain decreased with increasing baseline abdominal pain severity, with differences from placebo largest for patients with the lowest category of abdominal pain. Conclusion: Greater numbers of patients show a composite, abdominal pain, and stool consistency response with eluxadoline vs. placebo across baseline abdominal pain severity categories. This work was funded by Allergan plc.

Retrospective Chart Review Study of Patients Receiving Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) for Nutritional Management of Irritable Bowel Syndrome with Diarrhea (IBS-D)

Introduction: IBS-D is a common condition with few effective treatment options. The prescription medical food, SBI, has been shown to manage chronic loose and frequent stools in IBS-D patients. The safety and effectiveness of SBI as a therapy for IBS-D was further examined in this multi-center, IRB-reviewed study for overall and individual symptom response. Methods: Symptom data including stool frequency and consistency (Bristol Stool Scale 1-7), abdominal pain intensity (0 = no pain to 10 = worst pain) and adverse events (AEs) were collected from medical charts on 116 patients. Criteria for inclusion in primary analysis were patients having baseline recorded scores for stool consistency and abdominal pain, failure of standard-of-care (SOC) treatment, and not having received confounding IBS-D medications while on SBI. Results: The majority of patients who met criteria for analysis (n = 34) were white (94%), female (71%) with a median age of 53 (28, 85) and received SBI therapy for a mean duration of 23.2±24.1 wks [median 15.5 wks (0.4, 97.9)]. Mean baseline symptom scores were: stool frequency 5.24 (range 2 to 20); stool consistency 6.00 (range 4 to 7) and abdominal pain 4.56 (range 2 to 10). Twenty-five of the 34 patients had baseline abdominal pain scores >2 and stool consistency scores ≥ 5 to assess overall response; nine patients were excluded based on absence of pain (recorded score = 0) and normal stool score (Bristol Stool Scale = 4) at baseline. Of the 25 patients, 16 (64%) were responders with stool consistency < 5 and a 30% reduction in abdominal pain scores following SBI therapy. Using a generalized linear regression model for individual symptoms, the number of stools per day decreased by 3.24 (95% Confidence Interval (CI) 0.50, 5.98; P = 0.022), stool consistency improved by 1.86 (95% CI, 1.39, 2.33; P < 0.0001) and abdominal pain/discomfort intensity decreased by 3.03 (95% CI 1.668, 4.39; P < 0.0001). Thirteen of the 116 patients experienced one or more AEs while on SBI therapy. The main AEs were nausea (n = 5 patients) and an increase abdominal discomfort (n = 2 patients). No serious AEs were reported. Conclusion: Though retrospective, the inclusion criteria of SOC failure prior to SBI administration with demonstrated high combined abdominal pain and stool consistency response, as well as statistically significant individual symptom improvement, demonstrate SBI's clinical utility in IBS-D management. Additional chart reviews continue.

Nausea in Children With Functional Abdominal Pain Predicts Poor Health Outcomes in Young Adulthood.

Nausea is common among children with functional abdominal pain (FAP). We evaluated the relation of nausea to short- and long-term morbidity in pediatric patients with FAP. We performed a prospective study of 871 children with FAP (age, 8-17 y) seen in a pediatric gastroenterology practice; follow-up data were collected from 392 of the patients at 8.7 ± 3.3 years later. Participants were defined as having significant nausea if they reported nausea "a lot" or "a whole lot" within the past 2 weeks. Validated questionnaires assessed abdominal pain, gastrointestinal and somatic symptoms, and depression. Baseline measures, anxiety, and the Rome III criteria were assessed in the follow-up evaluation. At baseline, 44.8% of the patients reported significant nausea. Those with nausea reported worse abdominal pain, gastrointestinal symptoms, somatic symptoms, and depression than those without nausea (P < .001 for all). When the children had reached young adulthood, those with nausea in childhood continued to have more severe gastrointestinal (P < .001) and somatic symptoms (P= .003) than patients without nausea in childhood, as well as higher levels of anxiety (P= .02) and depression (P= .02). In the follow-up evaluation, somatic symptoms, depression, and anxiety remained significant after controlling for baseline abdominal pain severity. Pediatric patients with FAP and nausea have more severe short- and long-term gastrointestinal and somatic symptoms than patients with FAP without nausea, as well as reductions in mental health and daily function. Pediatric patients with FAP and nausea therefore need intensive treatment and follow-up evaluation.

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

Mo1262 Effects of Baseline Abdominal Pain on Response to Lubiprostone in Patients With Constipation-Predominant Irritable Bowel Syndrome

Background: IBS-D is characterized by a diverse group of core symptoms that include abdominal pain, altered stool consistency, bloating, and urgency. To assess the ability of rifaximin (RFX) to produce a common response to these multiple symptoms, the study design incorporated an open-label (OL) enrichment phase where RFX responders were identified for potential inclusion in a repeat treatment phase. This analysis describes the profile of symptom improvement from the OL enrichment phase. Methods: Subjects with IBS-D (Rome III criteria) with average symptom severity scores of ≥ 3 for abdominal pain (AP, scale 0-10) and bloating (scale 0-6), with ≥ 2 stools with Bristol Stool Scale (BSS) Type 6 (loose) or 7 (watery) during the 7-day baseline were entered into the OL phase. In OL, all subjects received RFX 550 mg TID for 2 weeks, followed by a 4-week, treatment-free assessment period. A responder, as defined by the FDA composite endpoint, was required to achieve a ≥30% decrease from baseline in mean weekly AP score, and simultaneously respond for stool consistency (SC) with a ≥50% decrease from baseline in number of days/ week with BSS Type 6 or 7 stools, for ≥2 weeks of a 4-week period. In addition to the FDA composite endpoint, additional core symptoms of IBS-D were assessed, including bloating (6-point scale; 0=not at all, 6=a very great deal), urgency (Yes/No during the last 24 hours), and overall IBS symptoms (How bothersome were your symptoms of IBS in the last 24 hours?; 6-point scale; 0 = not at all, 6 = a very great deal). Results: A total 2579 subjects (mean age: 46.4; 68% female) received RFX treatment during the OL phase, of which 2331 were evaluable for efficacy. Based on the pre-specified FDA composite definition of response, which stipulates improvements in both AP and SC on the same weeks, 1074 (46%) subjects were deemed responders in the 4-week follow-up period. Another 14% of subjects responded only to the SC component, while a different 11% of subjects responded only to the AP component. Finally, 1% of subjects experienced improvements for AP and SC, but not on the same weeks of the 4-week assessment period. Collectively, 72% of evaluable subjects experienced improvement on at least one component of the FDA composite endpoint. When all symptoms were evaluated independently (AP, SC, urgency, bloating, and overall IBS symptoms), >50% of subjects were deemed to be responders following a 2-week course of OL RFX (Table). Conclusions: These findings suggest that over 70% of patients experience improvement in at least one of the two symptoms of the FDA composite endpoint. Improvements for bloating, urgency, and overall IBS symptoms, suggest that the benefit of rifaximin may extend beyond symptoms comprising the FDA composite endpoint. Proportion of Responders for IBS-D Symptoms During Open-label Phase

Mo1834 Health Care Utilization and Costs Related to Eosinophilic Esophagitis in the United States Represent a Significant Burden of Disease

Background: The primary pharmacologic treatment modality for EoE is swallowed topical steroids. The factors which predict failure of steroid treatment have been poorly explored. Aim: To determine the frequency and identify predictors of histologic non-response to topical steroid administration in patients with EoE.Methods: This was a retrospective cohort study of the UNC EoE Clinicopathologic database from 2001-2013. Subjects with an incident diagnosis of EoE who met consensus guidelines, including non-response to a PPI trial, were included. Patients were identified who were treated with 2 months of a topical steroid (fluticasone 880-1760mcg/day or budesonide 1-2mg/day). Demographic and pre/post-treatment symptom (patient-reported global improvement), endoscopic (endoscopist-reported improvement), and histologic data were extracted from medical records. Responders were defined by a post-treatment eosinophil count <15 eos/hpf (hpf=0.24mm2) and compared to non-responders. Multivariate logistic regression was performed to assess predictors of response. Sensitivity analysis with different response thresholds (<5 eos/hpf; 0 eos/hpf) was also performed. Results: Of 455 EoE patients, 307 were treated with topical steroids, and 189 met inclusion criteria. Those who had a steroid response (n=109, 58%) did not differ from non-responders (n=80, 42%) on age (28 vs 25, p=0.23), gender (72% vs 70% male, p=0.82), or race (87% vs 78% White, p=0.08). Responders were more likely to have abdominal pain (23% vs 8%, p=0.005), but did not differ on other symptoms, symptom duration, or rates of atopic disease (see Table). Baseline endoscopic findings were similar between groups. Non-responders were almost twice as likely to have undergone dilation at baseline (36% vs 19, p=0.008). Baseline eosinophil counts were similar (76 vs 73 eos/hpf, p=0.80), as were doses of fluticasone and budesonide. Patients with <15 eos/hpf on treatment had better symptom response (87% vs 60%, p<0.001) and EGD response (92% vs 47%, p<0.001). After multivariate analysis, baseline abdominal pain predicted steroid response (OR 3.27 [1.25, 8.57]), while non-White race (OR 0.42 [0.19, 0.96] and baseline dilation (OR 0.42 [0.21, 0.85]) predicted non-response. Results were similar on sensitivity analysis when different histologic response thresholds were used. Conclusions: In this large cohort of EoE patients treated with topical steroids, histologic non-response was common. White race, abdominal pain, and dilation at the initial endoscopy were independently associated with decreased histological response. It is possible that dilation was a marker of more severe disease or that the more open post-dilation esophagus resulted in increased clearance of medication. These response data can help guide therapeutic decisions, particularly when weighing dietary and steroid therapy. Comparison of Histologic Responders (<15 eos/hpf) to Non-Responders (≥ 15 eos/hpf)

MAI, The Other Mycobacterium, as a Complication from Anti-TNF Therapy in IBD

Purpose: The patient is a 61-year-old male who presented with several weeks of malaise, weight loss, and several days of vomiting. He has a 25-year history of fibrostenotic Crohn's disease, for which he underwent an ileo-cecectomy in the past. Six months prior to presentation, the patient began having weight loss, abdominal pain, and was found to have strictures and ulcers in his small bowel. He had a negative Quantiferon Gold, and was started on infliximab therapy, 5 mg/kg with a standard initiation protocol. He received a total of six infusions prior to the current presentation, most recently 3 weeks prior. He was not taking any other medications for IBD, including a 5-ASA, immunologic or steroids. On presentation, the patient reported no fever, chills, nightsweats or cough. He had his baseline abdominal pain, but continued to have regular flatus and bowel movements, as well as a normal appetite. His physical exam demonstrated a thin man with notable pallor. His oropharynx was clear, and there was no palpable cervical lymphadenopathy. He had ronchi in his right lower lobe with deep inspiration. Abdominal exam was notable for a scaphoid abdomen with mild tympanic distention, and hyperactive bowel sounds. On labs, his WBC was 12.2 K/uL with a slight left shift, and his hemoglobin was 7.5 g/dL. He had a CT of the abdomen performed, where a 3-cm mass-like opacity was seen at the right lung base abutting the pleura. He also has some thickened small bowel loops in the left upper quadrant. Microbiology data was negative for legionella or strep pneumonia, as well as negative for histoplasmosis. The patient then underwent a video-assisted thoracic surgery with removal of the mass lesion. Pathology revealed areas of fibrosis, inflammation and foci with multinucleated giant cells suggestive of granulomas. Stains for AFB and fungus were negative. On sputum cultures, one-sixth grew Micobacterium avium-intracellulare (MAI). The patient was subsequently begun on multidrug treatment of his MAI with resolution of his symptoms and return to his normal weight. Anti-TNF therapy is a well-known risk factor for tuberculosis and other granulomatous diseases. Nontuberculosis mycobacterium has been reported in rheumatologic patients, usually in those taking corticosteroids or methotrexate concomitantly, but a specific warning or testing for MAI is not standard of care for IBD patients receiving anti-TNF therapy.