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.

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.

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.

Maintenance of clinical remission with biologics and small molecules in inflammatory bowel disease according to trial design: Meta-analysis.

BACKGROUND AND AIMS: Design of randomised controlled trials (RCTs) examining maintenance of clinical remission in inflammatory bowel disease (IBD) varies, with some trials re-randomising patients who have responded to active drug during induction to either active drug or placebo and others treating patients through with active drug or placebo from baseline. Whether this influences therapeutic gain of drug over placebo is unknown. METHODS: We searched the literature to January 2023 for maintenance of remission trials of biologics or small molecules versus placebo in IBD. We extracted maintenance of remission rates according to trial design; either trials re-randomising patients or trials treating patients through. We pooled data in a meta-analysis for all patients, and according to type of IBD. We calculated the number needed to treat (NNT), with a 95% confidence interval (CI), to assess therapeutic gain of active drug over placebo according to trial design. RESULTS: We identified 37 maintenance of remission trials (12,075 patients). Rates of maintenance of clinical remission were higher (41.9% with active drug, versus 20.3% with placebo), and NNT lowest (5; 95% CI 4-6), in trials re-randomising patients compared with those treating through (maintenance of remission rate 30.9% with active drug versus 14.6% with placebo, NNT = 7; 95% CI 5-9). Results were similar when trials were analysed according to IBD type but were more marked in ulcerative colitis RCTs (maintenance of remission rates in re-randomised trials 39.4% with active drug versus 17.8% with placebo, NNT = 5; 95% CI 3-7; treat-through trials 27.3% with active drug versus 11.9% with placebo, NNT = 7; 95% CI 5-11.5). CONCLUSION: Trials re-randomising patients had generally higher maintenance of remission rates, lower NNTs, and greater therapeutic gains over placebo.

Novel symptom clusters predict disease impact and healthcare utilisation in inflammatory bowel disease: Prospective longitudinal follow-up study.

BACKGROUND: Predicting adverse disease outcomes and high-volume users of healthcare amongst patients with inflammatory bowel disease (IBD) is difficult. AIMS: The aim of this study is to use latent class analysis to create novel clusters of patients and to assess whether these predict outcomes during 6.5 years of longitudinal follow-up. METHODS: Baseline demographic features, disease activity indices, anxiety, depression, and somatoform symptom-reporting scores were recorded for 692 adults. Faecal calprotectin (FC) was analysed at baseline in 348 (50.3%) patients (<250 mcg/g defined biochemical remission). Using baseline gastrointestinal and psychological symptoms, latent class analysis identified specific patient clusters. Rates of glucocorticosteroid prescription or flare, escalation, hospitalisation, or intestinal resection were compared between clusters using multivariate Cox regression. RESULTS: A three-cluster model was the optimum solution; 132 (19.1%) patients had below-average gastrointestinal and psychological symptoms (cluster 1), 352 (50.9%) had average levels of gastrointestinal and psychological symptoms (cluster 2), and 208 (30.1%) had the highest levels of both gastrointestinal and psychological symptoms (cluster 3). Compared with cluster 1, cluster 3 had significantly increased risk of flare or glucocorticosteroid prescription (hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.46-3.10), escalation (HR: 1.92; 95% CI: 1.34-2.76), a composite of escalation, hospitalisation, or intestinal resection (HR: 2.05; 95% CI: 1.45-2.88), or any of the endpoints of interest (HR: 2.06; 95% CI: 1.45-2.93). Healthcare utilisation was highest in cluster 3. CONCLUSIONS: Novel model-based clusters identify patients with IBD at higher risk of adverse disease outcomes who are high-volume users of healthcare.

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.

Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis.

BACKGROUND: There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. METHODS: We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score RESULTS: Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo. CONCLUSIONS: Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy.

Irritable bowel syndrome and mental health comorbidity - approach to multidisciplinary management.

Irritable bowel syndrome (IBS) affects 5-10% of the global population. Up to one-third of people with IBS also experience anxiety or depression. Gastrointestinal and psychological symptoms both drive health-care use in people with IBS, but psychological comorbidity seems to be more important for long-term quality of life. An integrated care approach that addresses gastrointestinal symptoms with nutrition and brain-gut behaviour therapies is considered the gold standard. However, best practice for the treatment of individuals with IBS who have a comorbid psychological condition is unclear. Given the rising prevalence of mental health disorders, discussion of the challenges of implementing therapy for people with IBS and anxiety and depression is critical. In this Review, we draw upon our expertise in gastroenterology, nutrition science and psychology to highlight common challenges that arise when managing patients with IBS and co-occurring anxiety and depression, and provide recommendations for tailoring clinical assessment and treatment. We provide best practice recommendations, including dietary and behavioural interventions that could be applied by non-specialists and clinicians working outside an integrated care model.

A prospective comparison of UK and Malaysian patients with irritable bowel syndrome in secondary care.

BACKGROUND: The prevalence of irritable bowel syndrome (IBS) is now known to be similar in various geographical regions, but there has been no study directly comparing characteristics of patients with IBS between populations. AIMS: To evaluate clinical and psychological differences between adults with IBS seen in secondary care in the United Kingdom (UK) and Malaysia. METHODS: Age- and sex-matched patients with IBS from a single centre in the UK (Leeds) and two centres in Malaysia (Kuala Lumpur and Kota Bharu), who fulfilled Rome III criteria, were recruited prospectively. Demographic characteristics and gastrointestinal and psychological symptoms were compared between both groups. RESULTS: A total of 266 (133 UK and 133 Malaysian) age- and sex-matched patients with Rome III IBS were recruited (mean age: 45.1 years Malaysia, vs. 46.5 years UK; 57.9% female). UK patients were more likely to consume alcohol than Malaysian patients (54.1% vs. 10.5%, p < 0.001). Compared with Malaysian patients, UK patients had more frequent abdominal pain, abdominal bloating, meal-related symptoms (p < 0.001 for all), higher symptom scores (mean 268.0 vs 166.0; p < 0.001), greater limitation of activities due to IBS (p = 0.007) and were more likely to report abnormal anxiety scores (p < 0.001). Higher perceived stress (mean 21.3 vs. 19.1, p = 0.014) and gastrointestinal symptom-specific anxiety scores (mean 50.8 vs. 43.0, p < 0.001) were also observed in UK patients. Finally, UK patients had higher somatoform symptom-reporting scores (mean 8.9 vs. 6.9, p < 0.001). CONCLUSIONS: IBS is more severe and is associated with a higher level of psychological symptoms in the UK compared with Malaysian patients in secondary care.

A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria. METHODS: We collected complete symptom data from 373 well-characterized adults meeting Rome IV criteria for IBS referred to a single UK clinic between September 2016 and March 2020. All patients underwent relatively standardized work-up to exclude relevant organic disease before diagnosis. We followed these individuals up to December 2022, assessing rates of rereferral, reinvestigation, and missed organic gastrointestinal disease. RESULTS: During a mean follow-up of 4.2 years per patient (total follow-up in all patients, 1565 years), 62 (16.6%) patients were rereferred. Of these, 35 (56.5%) were rereferred for IBS and 27 (43.5%) for other gastrointestinal symptoms. Among the 35 rereferred with IBS this was caused by a change in symptoms in only 5 (14.3%). Reinvestigation was undertaken in 21 (60.0%) of 35 rereferred with IBS and 22 (81.5%) of 27 rereferred with other symptoms (P = .12). Only 4 (9.3% of those reinvestigated and 1.1% of the entire cohort) new cases of relevant organic disease, which may have been responsible for IBS symptoms at baseline, were identified (1 case of chronic calcific pancreatitis among those rereferred with IBS and 1 case each of inflammatory bowel disease-unclassified, moderate bile acid diarrhea, and small bowel obstruction among those rereferred with other gastrointestinal symptoms). CONCLUSIONS: Despite rereferral for gastrointestinal symptoms among 1 in 6 patients overall, with almost 10% rereferred with ongoing IBS symptoms, and substantial reinvestigation rates, missed organic gastrointestinal disease occurred in only 1%. A diagnosis of Rome IV IBS after limited investigation is safe and durable.