Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically. METHODS: We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score. RESULTS: We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry. CONCLUSIONS: Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.

Utility of irritable bowel syndrome subtypes and most troublesome symptom in predicting disease impact and burden.

BACKGROUND: Little is known about the characteristics of individuals with irritable bowel syndrome (IBS) according to stool subtype or the most troublesome symptom reported by the individual, or whether these are useful in predicting the impact of IBS. METHODS: We collected demographic, gastrointestinal, and psychological symptoms, healthcare usage and direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. KEY RESULTS: We recruited 752 people with Rome IV IBS. Individuals with IBS-D reported a poorer disease-specific quality of life than those with IBS-C or IBS-M (mean (SD) IBS-QOL 45.3 (23.0) for IBS-D, vs. 52.3 (19.9) for IBS-C, vs. 49.4 (22.0) for IBS-M, p = 0.005). Mean (SD) IBS-QOL scores were also lower amongst those who reported diarrhea (44.8 (22.3)) or urgency (44.6 (22.3)) as their most troublesome symptom, compared with those reporting abdominal pain (52.2 (22.9)), constipation (49.5 (21.8)), or abdominal bloating or distension (50.4 (21.3)). However, there were no differences in mean EQ-5D scores, IBS severity, levels of anxiety, depression, somatoform symptom-reporting, or gastrointestinal symptom-specific anxiety. Direct healthcare costs of IBS were similar across all subtypes and all most troublesome symptom groups, although some differences in work productivity and social leisure activities were detected. CONCLUSIONS AND INFERENCES: There appears to be limited variation in the characteristics of individuals with Rome IV IBS based on both stool subtypes and most troublesome symptom reported, suggesting that gastrointestinal symptoms alone have limited ability to predict disease impact and burden.

Assessing Diagnostic Performance of Modifications to the Rome IV Criteria for Irritable Bowel Syndrome.

The gold standard symptom-based criteria for diagnosis of irritable bowel syndrome (IBS) are the Rome IV criteria.1 These are more restrictive than their predecessor, Rome III, because the cardinal feature required to meet criteria for IBS was changed to presence of abdominal pain alone, rather than abdominal pain or discomfort.2 This change was made because discomfort was believed to be an ambiguous term, with no equivalent in some languages. In addition, symptom frequency required for the presence of abdominal pain was increased to 1 day per week from 2 to 3 days per month. This has led to reduced sensitivity for detecting IBS and a 50% decrease in the prevalence of the disorder in the community.3,4 In a cross-sectional survey applying both Rome IV and III criteria to people living with IBS, 89% of those with Rome III-defined IBS not meeting Rome IV criteria did not meet Rome IV criteria because of this change in pain frequency.5 Previous iterations of the Rome criteria have performed only modestly in predicting a diagnosis of IBS.6-8 However, in a validation study, the Rome IV criteria outperformed Rome III,9 largely because their more restrictive nature made them more specific than Rome III. We assessed whether modifications to the Rome IV criteria led to a better trade-off between sensitivity and specificity.

Novel Symptom Subgroups in Individuals With Irritable Bowel Syndrome Predict Disease Impact and Burden.

BACKGROUND & AIMS: Current classification systems based on bowel habit fail to capture the multidimensional nature of irritable bowel syndrome (IBS). We previously derived and validated a classification system, using latent class analysis, incorporating factors beyond bowel habit. We applied this in another cohort of people with IBS to assess its ability to capture the impact of IBS on the individual, the health care system, and society. METHODS: We collected demographic, symptom, and psychological health data from adults in the community self-identifying as having IBS, and meeting Rome IV criteria. We applied our latent class analysis model to identify the 7 subgroups (clusters) described previously, based on overall gastrointestinal symptom severity and psychological burden. We assessed quality of life, health care costs (£1 = $1.20), employment status, annual income, work productivity, and ability to perform work duties in each cluster. RESULTS: Of 1278 responders, 752 (58.8%) met Rome IV criteria. The 7-cluster model fit the data well. The patients in the 4 clusters with the highest psychological burden, and particularly those in cluster 6 with high overall gastrointestinal symptom severity and high psychological burden, showed lower educational levels, higher gastrointestinal symptom-specific anxiety, were more likely to have consulted a gastroenterologist, and used more drugs for IBS. IBS-related and generic quality of life were impaired significantly in these 4 clusters and significantly fewer individuals reported earning ≥£30,000 per year. Productivity and the ability to work, manage at home, engage in social and private leisure activities, and maintain close relationships all were impacted significantly, and IBS-related health care costs over the previous 12 months were highest in these 4 clusters. In those in cluster 6, costs were more than £1000 per person per year. CONCLUSIONS: Our clusters identify groups of individuals with significant impairments in quality of life, earning potential, and ability to work and function socially, who are high utilizers of health care.

Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome.

BACKGROUND & AIMS: Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS. METHODS: We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials. CONCLUSIONS: Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.

Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Some probiotics may be beneficial in irritable bowel syndrome (IBS), but differences in species and strains used, as well as endpoints reported, have hampered attempts to make specific recommendations as to which should be preferred. We updated our previous meta-analysis examining this issue. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to March 2023). Randomized controlled trials (RCTs) recruiting adults with IBS, comparing probiotics with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk of global symptoms, abdominal pain, or abdominal bloating or distension persisting after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized mean difference with a 95% CI. Adverse events data were also pooled. RESULTS: We identified 82 eligible trials, containing 10,332 patients. Only 24 RCTs were at low risk of bias across all domains. For global symptoms, there was moderate certainty in the evidence for a benefit of Escherichia strains, low certainty for Lactobacillus strains and Lactobacillus plantarum 299V, and very low certainty for combination probiotics, LacClean Gold S, Duolac 7s, and Bacillus strains. For abdominal pain, there was low certainty in the evidence for a benefit of Saccharomyces cerevisae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains. For abdominal bloating or distension there was very low certainty in the evidence for a benefit of combination probiotics and Bacillus strains. The relative risk of experiencing any adverse event, in 55 trials, including more than 7000 patients, was not significantly higher with probiotics. CONCLUSIONS: Some combinations of probiotics or strains may be beneficial in IBS. However, certainty in the evidence for efficacy by GRADE criteria was low to very low across almost all of our analyses.

Antibiotics and Probiotics for Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a disorder of a gut-brain interaction characterised by abdominal pain and a change in stool form or frequency. Current symptom-based definitions and the classification of IBS promote heterogeneity amongst patients, meaning that there may be several different pathophysiological abnormalities leading to similar symptoms. Although our understanding of IBS is incomplete, there are several indicators that the microbiome may be involved in a subset of patients. Techniques including a faecal sample analysis, colonic biopsies, duodenal aspirates or surrogate markers, such as breath testing, have been used to examine the gut microbiota in individuals with IBS. Because of a lack of a clear definition of what constitutes a healthy gut microbiota, and the fact that alterations in gut microbiota have only been shown to be associated with IBS, a causal relationship is yet to be established. We discuss several hypotheses as to how dysbiosis may be responsible for IBS symptoms, as well as potential treatment strategies. We review the current evidence for the use of antibiotics and probiotics to alter the microbiome in an attempt to improve IBS symptoms. Rifaximin, a non-absorbable antibiotic, is the most studied antibiotic and has now been licensed for use in IBS with diarrhoea in the USA, but the drug remains unavailable in many countries for this indication. Current evidence also suggests that certain probiotics, including Lactobacillus plantarum DSM 9843 and Bifidobacterium bifidum MIMBb75, may be efficacious in some patients with IBS. Finally, we describe the future challenges facing us in our attempt to modulate the microbiome to treat IBS.

Prevalence and impact of faecal incontinence among individuals with Rome IV irritable bowel syndrome.

BACKGROUND: Little is known about faecal incontinence (FI) in individuals with irritable bowel syndrome (IBS). AIMS: To compare characteristics of people with IBS reporting FI, compared with people with IBS who do not report FI. METHODS: We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. We asked participants about FI, assigning presence or absence according to Rome-IV criteria. RESULTS: Of 752 participants with Rome IV IBS, 202 (26.9%) met Rome IV criteria for FI. Individuals with FI were older (p < 0.001), more likely to have IBS-D (47.0% vs. 39.0%, p = 0.008), and less likely to have attained a university or postgraduate level of education (31.2% vs. 45.6%, p < 0.001), or to have an annual income of ≥£30,000 (18.2% vs. 32.9%, p < 0.001). They were more likely to report urgency (44.6% vs. 19.1%, p < 0.001) as their most troublesome symptom and a greater proportion had severe IBS symptom scores, abnormal depression scores, higher somatic symptom-reporting scores or higher gastrointestinal symptom-specific anxiety scores (p < 0.01 for trend for all analyses). Mean health-related quality of life scores were significantly lower among those with, compared with those without, FI (p < 0.001). Finally, FI was associated with higher IBS-related direct healthcare costs (p = 0.002). CONCLUSIONS: Among individuals with Rome IV IBS, one-in-four repo rted FI according to Rome IV criteria. Physicians should ask patients with IBS about FI routinely.

Factors associated with lower disease-specific and generic health-related quality of life in Rome IV irritable bowel syndrome.

BACKGROUND: Little is known about associations with reduced quality of life in irritable bowel syndrome (IBS) or impact of IBS on quality of life compared with other chronic conditions. METHODS: We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living data from 752 individuals with Rome IV-defined IBS. We used the irritable bowel syndrome quality of life (IBS-QOL) and the EQ-5D-5L questionnaires to examine characteristics associated with lower quality of life. RESULTS: The mean IBS-QOL among all 752 individuals with Rome IV IBS was 48.4 (SD 22.3) and the mean EQ-5D score was 0.570 (SD 0.283), the latter being comparable to people with stroke, leg ulcers or chronic obstructive pulmonary disease. Lower levels of both disease-specific and generic quality of life were associated with severe IBS symptom scores, abnormal anxiety or depression scores, and higher somatoform symptom-reporting and gastrointestinal symptom-specific anxiety scores (p < 0.001 for all analyses). Those with lower quality of life had significantly higher healthcare usage and direct healthcare costs and more impairment in work and activities of daily living (p < 0.01 for all analyses). Avoidance of alcohol, lower educational level, abnormal anxiety, depression or somatoform symptom-reporting scores, and impairment in social leisure activities, home management or maintaining close relationships were all independently associated with lower quality of life. CONCLUSION: IBS has a substantial impact on the quality of life of those affected, and worse than observed in some severe chronic organic conditions.

Willingness to pay for medications among patients with Rome IV Irritable Bowel Syndrome.

BACKGROUND: Little is known about willingness to pay for medications among individuals with irritable bowel syndrome (IBS). METHODS: We collected demographic, gastrointestinal symptom, psychological health, quality of life, and healthcare usage data from 752 adults with Rome IV-defined IBS. We examined willingness to pay for a hypothetical medication in return for improvement in IBS symptoms using a contingent valuation method, according to these variables. RESULTS: The median amount of money individuals was willing to pay was £1-£50 (IQR £0-£100) per month for a medication with a 100% chance of improving IBS symptoms. Women, compared with men, (92.7% willing to pay "£0," 89.8% "£1-£50," 87.3% "£51-£100," 78.9% "£101-£200," and 78.5% "more than £200," p = 0.008) were less likely to be willing to pay for a pill with a 100% chance of improving IBS symptoms whilst those with an annual income of £30,000 or more (12.2% willing to pay "£0," 25.2% "£1-£50," 33.5% "£51-£100," 40.2% "£101-£200," and 35.1% "more than £200," p = 0.002) were more likely. We observed a higher willingness to pay among those with lower IBS-related quality of life (p = 0.002 for trend). Of all 752 individuals, 92.7%, 74.5%, and 58.0% would be willing to pay for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms, respectively. CONCLUSION: Patients with IBS are willing to pay for medications which improve IBS symptoms. Future studies should investigate the relative importance of medication pricing, efficacy, and side effect profile among individuals with IBS.

Impact of Rome IV irritable bowel syndrome on work and activities of daily living.

BACKGROUND: Few studies have demonstrated the impact of irritable bowel syndrome (IBS) on work and activities of daily living. METHODS: We collected demographic, gastrointestinal symptom, psychological health and quality of life data from 752 adults with Rome IV-defined IBS. We used the work productivity and activity impairment questionnaire for irritable bowel syndrome and the work and social adjustment scale to examine the degree of both impairment at work and in activities of daily living, as well as factors associated with these. RESULTS: Of 467 individuals who were employed, 133 (28.5%) reported absenteeism, 373 (85.6%) presenteeism and 382 (81.8%) overall work impairment. A mean of 1.97 hours of work per week was lost due to IBS. Extrapolating this across the entire UK, we estimate that between 72 and 188 million hours of work are lost per year due to IBS in individuals of working age. Among all 752 participants, 684 (91.0%) reported any activity impairment with 220 (29.3%) reporting impairment in home management, 423 (56.3%) in social leisure activities, 207 (27.5%) in private leisure activities, and 203 (27.0%) in maintaining close relationships. Severe IBS, higher levels of anxiety, depression, somatization and gastrointestinal symptom-specific anxiety, and lower levels of IBS-related quality of life were associated with impairment in both work and activities of daily living. CONCLUSION: Patients with IBS experience a substantial impact on their work and activities of daily living because of their IBS. Future studies should assess the impact of medical interventions on the ability to work and participate in social activities.

Direct healthcare costs of Rome IV or Rome III-defined irritable bowel syndrome in the United Kingdom.

BACKGROUND: Previous studies have demonstrated a substantial economic impact of irritable bowel syndrome (IBS). AIMS: To provide contemporaneous estimates of direct healthcare costs of IBS in the United Kingdom. METHODS: We collected demographic, gastrointestinal and psychological symptoms, quality of life and healthcare usage data from adults with Rome IV or Rome III IBS in the United Kingdom. We calculated the mean annual direct healthcare costs of IBS per person and used contemporaneous IBS prevalence data, together with census data, to estimate annual direct costs of IBS. We also examined predictors of higher costs. RESULTS: The mean annual direct cost of IBS per person among 752 individuals with Rome IV IBS was £556.65 (SD £1023.92) and £474.16 (SD £897.86) for 995 individuals with Rome III IBS. We estimate the annual direct healthcare cost of IBS in the United Kingdom is £1.27 billion if the Rome IV criteria are used to define IBS, and £2.07 billion using Rome III. Among individuals with Rome IV IBS, mean annual costs were higher in those with opiate use (£907.90 vs £470.58, p < 0.001), more severe symptoms (p < 0.001 for trend), a shorter duration of IBS (1 year, £1227.14 vs >5 years £501.60, p = 0.002), lower quality of life (p < 0.001 for trend), and higher depression, somatisation and gastrointestinal symptom-specific anxiety scores (P < 0.001 for trend for all). CONCLUSION: We estimate annual direct healthcare costs of IBS of between £1.3 and £2 billion in the United Kingdom.