Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease.

BACKGROUND: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS: We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 µg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES: Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

Symptomatic Response to Antibiotics in Patients With Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-analysis.

Background/Aims: We performed a systematic review and meta-analysis evaluating the symptomatic response rate to antibiotics in patients with small intestinal bacterial overgrowth (SIBO). Similarly, we performed a meta-analysis on the symptomatic response to antibiotics in irritable bowel syndrome (IBS) patients with and without SIBO. Methods: MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched from inception to March 2021. Randomized controlled trials and prospective studies reporting dichotomous outcomes were included. Results: There were 6 studies included in the first meta-analysis comparing the efficacy of antibiotics to placebo or no antibiotic. This included 196 patients, of whom 101 received antibiotics and 95 received placebo or no antibiotics. Significantly more patients improved with antibiotics (relative risk [95% CI] = 2.46 [1.33-4.55], P = 0.004). There were 4 studies included in the analysis comparing symptomatic response rates in IBS patients with or without SIBO with 266 IBS patients, of whom 172 had SIBO and 94 did not. The pooled response rate for symptomatic response was 51.2% in the SIBO group vs 23.4% in the no SIBO group, respectively. Significantly more IBS patients with SIBO responded to antibiotics compared to those without SIBO (relative risk [95% CI] = 2.07 [1.40-3.08], P = 0.0003). Conclusions: Antibiotics appear to be efficacious in treating SIBO, although small sample sizes and poor data quality limit this interpretation. Symptomatic response rates also appear to be higher in IBS patients with SIBO. This may be the first example of precision medicine in IBS as opposed to our current empiric treatment approach. Large-multicenter studies are needed to verify the results.

Optimizing the Management Algorithm for Adults With Functional Constipation Failing a Fiber/Laxative Trial in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population. METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity. RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility. DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies.

Objective: This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week. Conclusion: In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO.

Long-term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO-3 study.

BACKGROUND: Tenapanor, a first-in-class, minimally systemic inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults based on two randomized, placebo-controlled, phase III studies (T3MPO-1 [NCT02621892], T3MPO-2 [NCT02686138]). The open-label T3MPO-3 extension study (NCT02727751) enrolled patients who completed these studies to investigate long-term safety and tolerability of tenapanor. METHODS: Patients who completed T3MPO-1 (16 weeks) or T3MPO-2 (26 weeks) were eligible for enrollment in T3MPO-3. Patients in T3MPO-3 received open-label tenapanor 50 mg twice a day for up to an additional 39 (T3MPO-1) or 26 (T3MPO-2) weeks. Treatment-emergent adverse events (TEAEs) were evaluated in the entire T3MPO-3 safety population and in patients who received a total of ≥52 weeks of tenapanor. KEY RESULTS: A total of 312 patients were enrolled in T3MPO-3; 90 received ≥52 weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received ≥52 weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received ≥52 weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO-3 study. CONCLUSIONS: Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS-C.

Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study.

BACKGROUND & AIMS: The estimated prevalence of irritable bowel syndrome (IBS) using Rome IV criteria in the United States (US) ranges from 4.7% to 5.3%, although these estimates arise from studies with relatively small sample sizes. This study assessed the prevalence of IBS and its associated burden of illness using a nationally representative data set with nearly 89,000 people in the US. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults aged ≥18 years old as a "national health survey." We recruited a representative sample of people in the US to complete the survey, which included the Rome IV IBS questionnaire, National Institutes of Health Patient-Reported Outcome Measurement Information System (PROMIS) gastrointestinal scales, and questions on health care-seeking behavior. RESULTS: Overall, 88,607 people completed the survey, of whom 5414 (6.1%) met Rome IV IBS criteria: mixed IBS (n = 1838 [33.9%]), constipation-predominant IBS (n = 1819 [33.6%]), diarrhea-predominant IBS (n = 1521 [28.1%]), and unsubtyped IBS (n = 236 [4.4%]). Women had higher odds for IBS compared with men, whereas racial/ethnic minorities had lower odds for IBS vs non-Hispanic Whites. Across the 3 main subtypes, 68.2% to 73.2% of people reported ever seeking care for their IBS symptoms, whereas 53.8% to 58.9% did so in the past 12 months. CONCLUSIONS: In this nationwide US survey, we found that Rome IV IBS is slightly more prevalent (6.1%) vs prior estimates (4.7%-5.3%). Additional research is needed to determine whether this higher prevalence is in part due to the coronavirus disease 2019 pandemic during which this study was conducted.

Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of Helicobacter pylori infection.

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. Design: A comprehensive literature review and time-trend analysis. Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910). Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.

A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome.

BACKGROUND & AIMS: Gut-directed hypnotherapy (GDH) is effective for treating irritable bowel syndrome (IBS), but access limits its widespread use. We report the first randomized controlled trial comparing the safety and efficacy of a self-administered, digital GDH treatment program with that of digital muscle relaxation (MR) in adults with IBS. METHODS: After a 4-week run-in period, patients were randomized to 12 weeks of treatment with digital GDH (Regulora), or digital MR accessed via a mobile app on a smartphone or tablet. The primary endpoint was abdominal pain response, defined as ≥30% reduction from baseline in average daily abdominal pain intensity in the 4 weeks following treatment. Key secondary outcomes included mean change from baseline in abdominal pain, stool consistency, and stool frequency. RESULTS: Of 378 randomized patients, 362 were treated and included in the efficacy analysis. A similar proportion of the GDH (30.4%) and MR (27.1%) groups met the primary endpoint, with no significant difference between the groups (P = .5352). Significantly more patients treated with GDH than MR were abdominal pain responders during the last 4 weeks of treatment (30.9% vs 21.5%; P = .0232) and over the entire treatment period (29.3% vs 18.8%; P = .0254). Improvements in abdominal pain, stool consistency, and stool frequency were consistent across IBS subtypes. No patients experienced serious adverse events or adverse events leading to study discontinuation. CONCLUSIONS: Treatment with a digital GDH program led to an improvement in abdominal pain and stool symptoms in patients with IBS, supporting a role for this intervention as part of integrated care for IBS. CLINICALTRIALS: gov identifier NCT04133519.

Prevalence and Burden of Illness of Rome IV Chronic Idiopathic Constipation, Opioid-Induced Constipation, and Opioid-Exacerbated Constipation in the United States.

INTRODUCTION: Chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) are disorders that negatively affect quality of life. We sought to assess the prevalence, symptom severity, and medication use among people with Rome IV CIC, OIC, and opioid-exacerbated constipation (OEC) using a nationally representative data set with nearly 89,000 people in the United States. METHODS: From May 3, 2020, to June 24, 2020, we recruited a representative sample of people in the United States ≥ 18 years to complete an online national health survey. The survey guided participants through the Rome IV CIC and OIC questionnaires, Patient-Reported Outcome Measurement Information System gastrointestinal scales (percentile 0-100; higher = more severe), and medication questions. Individuals with OEC were identified by asking those with OIC whether they experienced constipation before starting an opioid and whether their symptoms worsened afterward. RESULTS: Among the 88,607 participants, 5,334 (6.0%) had Rome IV CIC, and 1,548 (1.7%) and 335 (0.4%) had Rome IV OIC and OEC, respectively. When compared with people with CIC (Patient-Reported Outcome Measurement Information System score, 53.9 ± 26.5; reference), those with OIC (62.7 ± 28.0; adjusted P < 0.001) and OEC (61.1 ± 25.8, adjusted P = 0.048) had more severe constipation symptoms. People with OIC (odds ratio 2.72, 95% confidence interval 2.04-3.62) and OEC (odds ratio 3.52, 95% confidence interval 2.22-5.59) were also more likely to be taking a prescription medication for their constipation vs those with CIC. DISCUSSION: In this nationwide US survey, we found that Rome IV CIC is common (6.0%) while Rome IV OIC (1.7%) and OEC (0.4%) are less prevalent. Individuals with OIC and OEC have a higher burden of illness with respect to symptom severity and prescription constipation medication use.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Overlap of disorders of gut-brain interaction: a systematic review and meta-analysis.

BACKGROUND: Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom categories frequently occurs. This systematic review and meta-analysis aimed to define the prevalence of DGBI overlap and compare overlap in population-based, primary care or tertiary care health settings. Furthermore, we aimed to compare symptom severity of psychological comorbidities in DGBI with and without overlap. METHODS: For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101). FINDINGS: 46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I2=99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001). INTERPRETATION: Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution. FUNDING: National Health and Medical Research Council and Centre for Research Excellence.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation.

BACKGROUND & AIMS: Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed. RESULTS: Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P = .001 for CSBM1; 22.7% vs 11.4% P = .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial. CONCLUSIONS: In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239).