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David J Gracie,1 Alexander C Ford1,2 1Leeds Gastroenterology Institute, St James’s University Hospital, 2Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK Abstract: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. Keywords: irritable bowel syndrome, ulcerative colitis, antidepressants, psychological therapies, probiotics

Background: Little is known about the natural history and impact of irritable bowel syndrome (IBS)-type symptoms on psychological health and quality of life in inflammatory bowel disease (IBD). We aimed to address this in a 12-month longitudinal follow-up study of secondary care patients., Methods: We collected demographic, Rome III IBS-type symptom, psychological, and quality of life data, with questionnaires at 3-month intervals, over 12 months of follow-up in patients with IBD in clinical remission at baseline. We assessed the natural history of Rome III IBS-type symptoms over the 12 months of the study and compared psychological and quality of life data between those reporting Rome III IBS-type symptoms at each of the points of follow-up with those not reporting such symptoms., Key Results: Among 206 patients with IBD in clinical remission at baseline (104 [50.5%] women, mean age 56.9 years [range 18-83 years], 79 [38.3%] Crohn's disease), 33 (16.0%) reported Rome III IBS-type symptoms at baseline and 72 (35.0%) reported Rome III IBS-type symptoms at one or more time points. Among the 33 patients with Rome III IBS-type symptoms at baseline, symptoms resolved in 6 (18.2%) patients, were present throughout in 6 (18.2%) patients, and fluctuated in the remaining 21 (63.6%) patients. Among the 39 patients with new onset of Rome III IBS-type symptoms after baseline, 24 (65.1%) had symptoms at one point in time only, 10 (25.6%) at two points, four (10.3%) at three points, and one (2.6%) at four points. At each point in time, reporting IBS-type symptoms was associated with significantly higher anxiety, depression, or somatoform symptom-reporting scores, and/or lower quality of life scores., Conclusions & Inferences: In this 12-month follow-up study, one-third of patients with IBD reported presence of Rome III IBS-type symptoms at any point in time. Reporting such symptoms was associated with significant impacts on psychological health and/or quality of life., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

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., Competing Interests: Conflict of interest Brigida Barberio: none. David J Gracie: none. Christopher J. Black: none. Alexander C Ford: none., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Opioid use is increasingly prevalent amongst patients with inflammatory bowel disease (IBD), but whether opioids have deleterious effects, or their use is merely linked with more severe disease, is unclear. We conducted a longitudinal follow-up study examining this issue., Methods: Data on demographics, gastrointestinal and psychological symptoms, quality of life, and opioid use were recorded at baseline. Data on healthcare use and adverse disease outcomes were obtained from a review of electronic medical records at 12 months. Characteristics at baseline of those using opioids and those who were not were compared, in addition to occurrence of flare, prescription of glucocorticosteroids, treatment escalation, hospitalization, or intestinal resection during the 12 months of follow-up., Results: Of 1029 eligible participants, 116 (11.3%) were taking opioids at baseline. Medium (odds ratio [OR], 4.67; 95% confidence interval [CI], 1.61-13.6) or high (OR, 8.03; 95% CI, 2.21-29.2) levels of somatoform symptom-reporting and use of antidepressants (OR, 2.54; 95% CI, 1.34-4.84) or glucocorticosteroids (OR, 6.63; 95% CI, 2.26-19.5; P < .01 for all analyses) were independently associated with opioid use. Following multivariate analysis, opioid users were significantly more likely to undergo intestinal resection (hazard ratio,  7.09; 95% CI, 1.63 to 30.9; P = .009), particularly when codeine or dihydrocodeine were excluded (hazard ratio, 42.9; 95% CI, 3.36 to 548; P = .004)., Conclusions: Opioid use in IBD is associated with psychological comorbidity and increased risk of intestinal resection, particularly in stronger formulations. Future studies should stratify the risk of individual opioids, so that robust prescribing algorithms can be developed and assess whether addressing psychological factors in routine IBD care could be an effective opioid avoidance strategy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Timings of assessment of efficacy and criteria used to define Crohn's disease (CD) activity at baseline may affect therapeutic gain of active drug over placebo in induction of remission trials in CD, but these issues have not been assessed systematically. We examined these issues in a meta-analysis., Methods: We searched the literature to June 2022 for randomized controlled trials of biologics vs placebo in active CD. We extracted clinical remission and response rates according to criteria used to define CD activity and time point of assessment, pooling them in a meta-analysis for all patients according to previous biologic exposure. 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 these characteristics of trial design., Results: We identified 20 induction of remission trials (6754 patients). Rates of clinical remission were highest (42.6% with active drug vs 21.0% with placebo) and NNT lowest (5; 95% CI, 3-7.5) in trials using clinical and endoscopic activity to define active CD. Rates of remission were lower (26.5% with active drug, vs 18.6% with placebo) and NNT highest (12; 95% CI, 6-61) in trials using clinical activity alone. Results were similar according to previous biologic exposure. Time point of assessment seemed to have less of an effect, although the NNT was lowest in trials assessing remission rates at 9 to 12 weeks (NNT = 5.5; 95% CI, 4-8). Again, results were similar according to previous biologic exposure., Conclusions: Both the criteria used to define CD activity at study entry and the time point used to confirm efficacy may be important in maximizing therapeutic gain of active drug over placebo., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is increasing evidence for an influence of the gut-brain axis on the natural history of inflammatory bowel disease (IBD). Psychological therapies could, therefore, have beneficial effects in individuals with IBD, but data are conflicting. We aimed to update our previous systematic review and meta-analysis to assess whether the inclusion of more randomised controlled trials (RCTs) showed any beneficial effects and whether these effects varied by treatment modality., Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials from Jan 1, 2016, to April 30, 2023, for RCTs published in any language recruiting individuals aged 16 years or older with IBD that compared psychological therapy with a control intervention or treatment as usual. We pooled dichotomous data to obtain relative risks (RR) with 95% CIs of inducing remission in people with active disease or of relapse in people with quiescent disease at final follow-up. We pooled continuous data to estimate standardised mean differences (SMD) with 95% CIs in disease activity indices, anxiety scores, depression scores, stress scores, and quality-of-life scores at completion of therapy and at final follow-up. We pooled all data using a random-effects model. Trials were analysed separately according to whether they recruited people with clinically active IBD or predominantly individuals whose disease was quiescent. We conducted subgroup analyses by mode of therapy and according to whether trials recruited selected groups of people with IBD. We used the Cochrane risk of bias tool to assess bias at the study level and assessed funnel plots using the Egger test. We assessed heterogeneity using the I 2 statistic., Findings: The updated literature search identified a total of 469 new records, 11 of which met eligibility criteria. 14 studies were included from our previous meta-analysis published in 2017. In total, 25 RCTs were eligible for this meta-analysis, all of which were at high risk of bias. Only four RCTs recruited patients with active IBD; there were insufficient data for meta-analysis of remission, disease activity indices, depression scores, and stress scores. In patients with active IBD, psychological therapy had no benefit compared with control for anxiety scores at completion of therapy (two RCTs; 79 people; SMD -1·04, 95% CI -2·46 to 0·39), but did have significant benefit for quality-of-life scores at completion of therapy (four RCTs; 309 people; 0·68, 0·09 to 1·26), although heterogeneity between studies was high (I 2 =82%). In individuals with quiescent IBD, RR of relapse of disease activity was not reduced with psychological therapy (ten RCTs; 861 people; RR 0·83, 95% CI 0·62 to 1·12), with moderate heterogeneity (I 2 =60%), and the funnel plot suggested evidence of publication bias or other small study effects (Egger test p=0·046). For people with quiescent IBD at completion of therapy, there was no difference in disease activity indices between psychological therapy and control (13 RCTs; 1015 people; SMD -0·01, 95% CI -0·13 to 0·12; I 2 =0%). Anxiety scores (13 RCTs; 1088 people; -0·23, -0·36 to -0·09; 18%), depression scores (15 RCTs; 1189 people; -0·26, -0·38 to -0·15; 2%), and stress scores (11 RCTs; 813 people; -0·22, -0·42 to -0·03; 47%) were significantly lower, and quality-of-life scores (16 RCTs; 1080 people; 0·31, 0·16 to 0·46; 30%) were significantly higher, with psychological therapy versus control at treatment completion. Statistically significant benefits persisted up to final follow-up for depression scores (12 RCTs; 856 people; -0·16, -0·30 to -0·03; 0%). Effects were strongest in RCTs of third-wave therapies and in RCTs that recruited people with impaired psychological health, fatigue, or reduced quality of life at baseline., Interpretation: Psychological therapies have beneficial, short-term effects on anxiety, depression, stress, and quality-of-life scores, but not on disease activity. Further RCTs in selected groups are needed to establish the place for such therapies in IBD care., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis., Design: We searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score., Results: We identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82)., Conclusion: In a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Symptoms of common mental disorders, such as anxiety or depression, are associated with adverse clinical outcomes in inflammatory bowel disease (IBD). We report trajectories of these symptoms in IBD, patient characteristics associated with different trajectories, and effects on healthcare utilization and prognosis., Methods: We collected demographic, symptom, psychological, and quality-of-life data, with questionnaires at 3-month intervals, over 12 months of follow-up. We collected healthcare utilization and IBD outcomes through notes review. We compared characteristics of those with persistently normal or improving anxiety or depression scores with those with persistently abnormal or worsening scores and the number of flares, glucocorticosteroid prescriptions, escalations of therapy, hospitalizations, or intestinal resections due to IBD activity., Results: Among 771 and 777 patients, respectively, worsening or persistently abnormal anxiety or depression scores were associated with increased antidepressant (28.6% vs 12.3% anxiety, 35.8% vs 10.1% depression, P < 0.001) and opiate use (19.0% vs 7.8% anxiety, P = 0.001 and 34.0% vs 7.4% depression, P < 0.001), compared with those with persistently normal or improving scores. These individuals were also more likely to have been diagnosed with IBD in the last 12 months (16.3% vs 5.0% anxiety, P = 0.001, and 15.1% vs 5.5% depression, P = 0.006), to have clinically active disease at baseline (57.1% vs 26.6% anxiety and 71.7% vs 29.1% depression, P < 0.001) and lower quality-of-life scores ( P < 0.001). Individuals with worsening or persistently abnormal trajectories of anxiety or depression required significantly more outpatient appointments, radiological investigations, and endoscopic procedures for IBD-related symptoms., Discussion: In this 12-month follow-up study, patients with IBD with worsening or persistently high anxiety or depression scores were higher utilizers of health care but were not at an increased risk of future adverse disease outcomes., (Copyright © 2022 by The American College of Gastroenterology.)

Background: The long-term natural history and impact of irritable bowel syndrome (IBS)-type symptoms on outcomes in inflammatory bowel disease (IBD) are uncertain., Aim: To assess this in a longitudinal follow-up study of patients in secondary care METHODS: We assessed the natural history of IBS-type symptoms in IBD via Rome III criteria applied at baseline, and 2 and 6 years. We defined longitudinal disease activity as the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. To assess healthcare utilisation, we recorded the number of outpatient clinic attendances and investigations. We also collected anxiety, depression and somatoform symptom scores and quality of life scores during follow-up., Results: Among 125 individuals with Rome III data at all three time points, only 41 (32.8%) never reported IBS-type symptoms. Fifteen patients (12.0%) had IBS-type symptoms at baseline that resolved, 19 (15.2%) had fluctuating symptoms, 35 (28.0%) had new-onset symptoms, and 15 (12.0%) had persistent symptoms. Among more than 300 patients with IBD activity data, IBS-type symptoms were not associated with an increased likelihood of the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. However, the mean numbers of outpatient appointments and endoscopic investigations were significantly higher among those with IBS-type symptoms. Anxiety, depression and somatoform symptom scores were significantly higher, and quality of life scores were significantly lower, in those reporting IBS-type symptoms at least once during the study., Conclusions: IBS-type symptoms affected more than two-thirds of patients with IBD during >6 years of follow-up and were associated with increased healthcare utilisation, and worse anxiety, depression, somatoform symptom and quality of life scores, but not adverse disease activity outcomes., (© 2022 John Wiley & Sons Ltd.)

Objective: The role of the brain-gut axis is of increasing interest in IBD, as the link between common mental disorders and GI inflammation may be bidirectional. We performed a systematic review examining these issues., Design: We searched EMBASE Classic and EMBASE, Medline, and APA PsychInfo (to 11 July 2021) for longitudinal follow-up studies examining effect of symptoms of anxiety or depression on subsequent adverse outcomes in IBD, or effect of active IBD on subsequent development of symptoms of anxiety or depression. We pooled relative risks (RRs) and HRs with 95% CIs for adverse outcomes (flare, escalation of therapy, hospitalisation, emergency department attendance, surgery or a composite of any of these) according to presence of symptoms of anxiety or depression at baseline, or RRs and HRs with 95% CIs for new onset of symptoms of anxiety or depression according to presence of active IBD at baseline., Results: We included 12 separate studies, recruiting 9192 patients. All 12 studies examined brain-to-gut effects. Anxiety at baseline was associated with significantly higher risks of escalation of therapy (RR=1.68; 95% CI 1.18 to 2.40), hospitalisation (RR=1.72; 95% CI 1.01 to 2.95), emergency department attendance (RR=1.30; 95% CI 1.21 to 1.39), or a composite of any adverse outcome. Depression at baseline was associated with higher risks of flare (RR=1.60; 95% CI 1.21 to 2.12), escalation of therapy (RR=1.41; 95% CI 1.08 to 1.84), hospitalisation (RR=1.35; 95% CI 1.17 to 1.57), emergency department attendance (RR=1.38; 95% CI 1.22 to 1.56), surgery (RR=1.63; 95% CI 1.19 to 2.22) or a composite of any of these. Three studies examined gut-to-brain effects. Active disease at baseline was associated with future development of anxiety or depression (RR=2.24; 95% CI 1.25 to 4.01 and RR=1.49; 95% CI 1.11 to 1.98, respectively)., Conclusion: Bidirectional effects of the brain-gut axis are present in IBD and may influence both the natural history of the disease and psychological health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Symptoms of common mental disorders, such as anxiety or depression, are common in inflammatory bowel disease (IBD) and may affect prognosis. However, unlike clinical or biochemical markers of disease activity, psychological health is not a recommended therapeutic target. We assessed relative contribution of poor psychological health and clinical or biochemical activity to prognosis., Methods: Demographic features, IBD subtype, treatments, and anxiety and depression scores were recorded at baseline for 760 adults, with clinical activity determined using validated scoring systems. Fecal calprotectin was analyzed in 379 (49.9%) patients (≥250 μg/g used to define biochemical activity). Glucocorticosteroid prescription or flare, escalation, hospitalization, intestinal resection, or death were assessed during 6.5 years of follow-up. Occurrence was compared using multivariate Cox regression across 4 patient groups according to presence of disease remission or activity, with or without symptoms of a common mental disorder, at baseline., Results: In total, 718 (94.5%) participants provided data. Compared with clinical remission without symptoms of a common mental disorder at baseline, need for glucocorticosteroid prescription or flare (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.58-3.54), escalation (HR, 1.65; 95% CI, 1.14--2.40), and death (HR, 4.99; 95% CI, 1.80-13.88) were significantly higher in those with clinical activity and symptoms of a common mental disorder. Rates in those with clinical remission and symptoms of a common mental disorder at baseline or those with clinical activity without symptoms of a common mental disorder were not significantly higher. Similarly, with biochemical activity and symptoms of a common mental disorder, rates of glucocorticosteroid prescription or flare (HR, 2.48; 95% CI, 1.38-4.46), escalation (HR, 2.97; 95% CI, 1.74-5.06), hospitalization (HR, 3.10; 95% CI, 1.43-6.68), and death (HR, 6.26; 95% CI, 2.23-17.56) were significantly higher., Conclusions: Psychological factors are important determinants of poor prognostic outcomes in IBD and should be considered as a therapeutic target., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Little is known about the differences between patients diagnosed with irritable bowel syndrome (IBS) by a physician who meet the Rome IV criteria for IBS and those who do not. We conducted a longitudinal follow-up study examining this., Methods: We collected complete gastrointestinal, extraintestinal, and psychological symptom data from 577 consecutive adult patients with suspected IBS in a single UK gastroenterology clinic. We compared baseline characteristics between patients who met Rome IV criteria for IBS, and those who had IBS according to a physician's diagnosis but who did not meet Rome IV criteria, as well as examining whether meeting Rome IV criteria at baseline influenced evolution of symptoms under therapy., Key Results: Of 455 patients diagnosed with IBS by a physician, 375 (82.4%) met Rome IV criteria and 80 (17.4%) did not. Those who met Rome IV criteria were more likely to report severe symptoms (67.6%, vs. 30.0%, p < 0.001) and that symptoms limited activities ≥50% of the time (63.0%, vs. 37.5%, p < 0.001). Patients with Rome IV IBS were more likely to have abnormal anxiety scores (50.8%, vs. 35.9%, p = 0.007) and higher levels of somatoform symptom-reporting (29.4%, vs. 12.5%, p < 0.001). Despite this, during longitudinal follow-up, there was no significant difference in mean number of appointments required subsequently, or IBS symptom severity., Conclusions and Inferences: Although patients who met the Rome IV criteria had more severe symptoms at baseline and were more likely to exhibit psychological comorbidity, they did not appear to have a worse prognosis than those with physician-diagnosed IBS., (© 2021 John Wiley & Sons Ltd.)

Background: Irritable bowel syndrome (IBS)-type symptoms are common in inflammatory bowel disease (IBD), but few studies have examined the prevalence and impact of IBS-type symptoms in IBD according to Rome IV criteria., Methods: We collected demographic, symptom (Rome III, Rome IV, and clinical disease activity indices), psychological (anxiety, depression, and somatization), and quality of life data from 973 IBD patients. Medical records were reviewed to document disease type, extent/location, behavior, medical therapy, and antidepressant or opioid use. We compared characteristics of individuals with no IBS-type symptoms, Rome III IBS-type symptoms, and Rome IV IBS-type symptoms., Key Results: In total, 302 (31.0%) patients met the Rome III criteria for IBS, and 172 (17.7%) met Rome IV criteria. Those with IBS-type symptoms were younger, more likely to be female, and had higher rates of antidepressant (p = 0.006) or opioid use (p = 0.001). Rome IV IBS-type symptoms were associated with symptoms of mood disorders, flare of disease activity, and lower quality of life scores (p < 0.001 for all analyses). Compared with Rome III criteria, those with Rome IV IBS-type symptoms had significantly higher rates of anxiety (p < 0.001), depression (p = 0.002), and somatization (p < 0.001), lower quality of life scores (p < 0.001) and were more likely to have CD (p = 0.011), with ileal distribution (p = 0.006)., Conclusions and Inferences: Rome IV IBS-type symptoms are associated with increased psychological co-morbidity, lower quality of life scores, and higher rates of antidepressant or opioid use. This is a cohort potentially at risk of adverse clinical outcomes and should be a focus for future research., (© 2021 John Wiley & Sons Ltd.)

Objective: Biological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis., Design: We searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score., Results: We identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91)., Conclusion: In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Psychological co-morbidity is more common in patients with inflammatory bowel disease (IBD), compared with the general population, but little is known about the cumulative effect of increasing psychological burden on disease behaviour., Aims: To examine the effect of psychological co-morbidity on inflammatory bowel disease in a longitudinal follow-up study., Methods: We collected complete demographic, symptom and psychological co-morbidity data (anxiety, depression and somatisation scores) at baseline from adults with IBD in biochemical remission (faecal calprotectin <250 µg/g). Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalisation or intestinal resection, were reviewed ≥2 years of follow-up. We performed multivariate Cox regression, controlling for patient characteristics and follow-up duration, to examine cumulative effect of psychological co-morbidities on subsequent IBD behaviour., Results: Among 218 participants, 48 (22.0%) had one, 13 (6.0%) two and nine (4.1%) three psychological co-morbidities at baseline. Following multivariate Cox regression analysis, glucocorticosteroid prescription or flare, and escalation of medical therapy were significantly higher among those with two (hazard ratio [HR] = 3.18; 95% confidence interval [CI] 1.44-7.02, and HR = 2.48; 95% CI 1.03-5.93, respectively) or three (HR = 3.53; 95% CI 1.26-9.92, and HR = 8.19; 95% CI 2.88-23.23, respectively) psychological co-morbidities. Occurrence of at least one endpoint of interest was significantly higher with increasing psychological co-morbidity (HR = 1.74; 95% CI 1.07-2.82 for one, HR = 2.47; 95% CI 1.12-5.46 for two and HR = 4.93; 95% CI 1.84-13.17 for three psychological co-morbidities)., Conclusions: Individuals with IBD in biochemical remission experienced a worse disease course with increasing psychological co-morbidity at baseline., (© 2021 John Wiley & Sons Ltd.)

Objectives: Despite being proposed 4 years ago, there has been no independent validation study of the Rome IV criteria for IBS. We assessed their performance for the diagnosis of IBS in secondary care and compared them with the previous iteration, the Rome III criteria., Design: We collected complete symptom data from consecutive adult patients with suspected IBS referred to a single UK clinic. All subjects underwent relatively standardised workup, with assessors blinded to symptom status. The reference standard used to confirm IBS was the presence of lower abdominal pain or discomfort in association with altered stool form or frequency, in a patient with no evidence of organic gastrointestinal disease after investigation. Sensitivity, specificity and positive and negative likelihood ratios (LRs), with 95% CIs, were calculated for each of the diagnostic criteria., Results: The level of agreement between the Rome IV and Rome III criteria was good (kappa=0.65). Compared with the reference standard, sensitivity and specificity of the Rome IV criteria in 572 patients (431 (75.3%) women, mean age 36.5 years) were 82.4% and 82.9%, respectively. Positive and negative LRs for the Rome IV criteria were 4.82 (95% CI 3.30 to 7.28) and 0.21 (95% CI 0.17 to 0.26), respectively. The Rome IV criteria performed best in those with IBS with constipation or mixed bowel habits. In 471 patients (350 (74.3%) women, mean age 36.7 years), compared with the reference standard, the sensitivity and specificity of the Rome III criteria were 85.8% and 65.0%; positive and negative LRs were 2.45 (95% CI 1.90 to 3.27) and 0.22 (0.16 to 0.29), respectively. Incorporating mood and extraintestinal symptom reporting into diagnostic criteria did not improve their performance significantly., Conclusions: The Rome IV criteria performed significantly better than the Rome III criteria in diagnosing IBS in this single centre secondary care study, although the clinical relevance of this is uncertain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Near-peer assisted learning (NPAL) has been welcomed in recent years as a favourable method for teaching medical students. It has proven advantages for both the educator and the learner. As such it was identified as an ideal approach for delivering the local curriculum within a paediatric surgical setting. Short duration of placements further suggests that structured tutorials would best guarantee coverage of the student curriculum. Our hypothesis was that the introduction of a structured programme such as this could lead to reduced dependence on senior staff for teaching, increased exposure of junior staff as educators, and increased coverage of the curriculum., Methods: Curriculum outcomes were identified, and a series of tutorials developed for delivery by juniors within the department. Pre and post intervention questionnaires were given to students rotating through the department., Results: 70 responses were analysed (23 pre; 47 post intervention). Reliance on Consultant teaching dropped 29% and engagement of surgical, GP and foundation trainees in teaching increased by 29%, 43% and 9% respectively. Overall curriculum coverage increased by 12%., Conclusion: A near-peer assisted tutorial programme is an effective way of increasing coverage of the medical curriculum with benefits for tutors and learners, whilst increasing junior engagement in teaching and reducing burden on Consultants.

Background: Therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies in conjunction with symptoms, disease history, and investigations can aid decision-making. This study evaluated 1-year outcomes of patients with decisions that were altered on the basis of TDM results, in order to investigate whether outcomes from TDM-based decisions to adjust or stop IFX treatment are durable., Methods: We retrospectively collected clinical outcomes 12 months post treatment decisions based on proactive TDM. Patients whose initial treatment decisions were altered on the basis of TDM results were compared with those where the decision remained unchanged. Events of interest were inpatient admissions with active inflammatory bowel disease (IBD), further changes to biologic therapy, and IBD-related health-care costs., Results: Of 189 patients, 54 (28%) had initial treatment decisions altered in the light of TDM results. The 135 patients whose initial decision was not altered in light of TDM results served as the comparator. There were no differences in hospitalization rates or subsequent biologic switches between the altered decision groups and the comparator group. IBD-related health-care costs were higher in those whose initial decision was altered (median GBP 7,912 vs. GBP 6,521; p < 0.0001) due to higher drug costs (median GBP 7,062 vs. GBP 6,012; p < 0.0001)., Conclusion: Our study demonstrates good outcomes from changes to IFX treatment based on TDM. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes but had higher drug-related expenditure than those whose treatment decision was not altered in light of TDM., Competing Interests: C.P.S. has received unrestricted research grants from Warner Chilcott, Janssen, and AbbVie, has provided consultancy to Warner Chilcott, Dr. Falk, AbbVie, Takeda, Fresenius Kabi, and Janssen, and had speaker arrangements with Warner Chilcott, Dr. Falk, AbbVie, MSD, Pfizer, and Takeda. T.A. has received unrestricted educational grants, consultancy fees, speaker fees, and support to attend conferences from AbbVie, MSD, NAPP, Pfizer, Janssen, and Takeda. P.J.H. has received speaker fees from AbbVie, Ferring, MSD, and Takeda, and fees for advisory boards from Warner Chilcott, Dr. Falk, AbbVie, Takeda, and Otsuka. D.J.G. has received speaker fees from Takeda and AbbVie. All other authors declare no conflict of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Background: Patients with inflammatory bowel disease (IBD) often report symptoms compatible with irritable bowel syndrome (IBS), which might have an effect on psychological health. However, previous estimates of the magnitude of this issue have not accounted for ongoing inflammation as the potential cause. We updated a previous systematic review and meta-analysis to determine prevalence of IBS-type symptoms in patients with IBD in remission to better quantify the magnitude of this issue., Methods: In this systematic review and meta-analysis, Embase, Embase Classic, and MEDLINE were searched (from Jan 1, 2012, to May 11, 2020) to identify prospective case-control or cross-sectional studies reporting prevalence of symptoms meeting diagnostic criteria for IBS in adults with IBD in remission. Studies were required to have recruited an unselected adult population (more than 90% of participants aged ≥16 years) with histologically or radiologically confirmed IBD and include at least 50 participants. Pooled prevalence and odds ratios (ORs) with 95% CIs were calculated according to the definition of remission, criteria used to define IBS-type symptoms, and type of IBD. The association between IBS-type symptom reporting and psychological comorbidity was examined using weighted mean difference (WMD) or standardised mean difference (SMD) in anxiety and depression scores between those reporting IBS-type symptoms and those not, for cases in which these data were available., Findings: Of 3370 studies identified, 27 were eligible, of which 18 were newly identified. Among 3169 patients with IBD in remission, pooled prevalence of IBS-type symptoms was 32·5% (95% CI 27·4-37·9; I 2 =90·1%). Prevalence was lower when remission was defined by endoscopic assessment (23·5%, 95% CI 17·9-29·6; I 2 =59·9%) or histological assessment (25.8%, 95% CI 20.2-31.7; I 2 =not applicable) than when defined by validated clinical disease activity index (33·6%, 26·3-41·2; I 2 =91·8%) and higher in Crohn's disease than in ulcerative colitis (36·6%, 29·5-44·0; I 2 =82·9% vs 28·7%, 22·9-34·8; I 2 =87·2%). Anxiety (WMD 2·5; 95% CI 0·8-4·3) and depression (SMD 0·64; 0·44-0·84) scores were significantly higher among those who reported IBS-type symptoms than in those who did not., Interpretation: Prevalence of symptoms compatible with IBS in patients with IBD varied according to how remission was defined. However, even when stringent criteria such as endoscopic or histological remission were used, about a quarter of patients reported these symptoms. Such symptoms were more common in patients with Crohn's disease and were associated with psychological comorbidity. Addressing psychological wellbeing might improve outcomes in this specific group of patients., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently., Methods: We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity., Key Results: As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe., Conclusions and Inferences: Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD., (© 2019 John Wiley & Sons Ltd.)

Brain-gut interactions affect psychological wellbeing and symptom reporting in functional gastrointestinal disorders; the presence of anxiety or depression is associated with the development of new-onset gastrointestinal symptoms, and the presence of gastrointestinal symptoms is associated with the development of psychological disorders de novo. In inflammatory bowel diseases (IBD), the reporting of irritable bowel syndrome (IBS)-type symptoms by patients with quiescent disease is common, and is associated with psychological disorders, impaired quality of life, and increased health-care use. In IBD, data from observational studies suggest that psychological disorders might be associated with relapse of disease activity, and that inflammatory activity is associated with the development of new psychological disorders, as has been described for functional gastrointestinal disorders such as IBS and functional dyspepsia. The brain-gut axis provides the physiological link between the CNS and gastrointestinal tract that might facilitate these relationships. In IBS, treatments targeting disordered brain-gut axis activity, including psychological therapies and antidepressants, might lead to improved symptoms and quality of life. However, in IBD, the benefit of these treatments is less certain because of a scarcity of interventional studies. Despite the scarcity of trials, observational data suggest that the effect of disordered brain-gut axis activity in IBD is substantial, and scope remains for further well designed trials of psychological therapies and antidepressants, particularly in the subset of patients who have coexistent psychological disorders, or in those who report IBS-type symptoms. Integrating these treatments into a biopsychosocial model of care has the potential to improve both psychological wellbeing and quality of life in some patients with IBD, reducing health-care use and altering the natural history of disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Fatigue is a frequent, debilitating symptom of inflammatory bowel disease (IBD). Despite this, studies report dissatisfaction among IBD patients regarding how little attention is given to fatigue-related issues during consultations. We performed a pilot randomized controlled trial (RCT) to assess whether a brief, structured, multidisciplinary psychological support program improved fatigue, mood and quality of life indices in patients with quiescent IBD., Methods: The intervention consisted of three small-group psychoeducational sessions over 6 months. Primary outcomes were effect on fatigue severity and impact scores. Secondary outcomes included effect on depression, anxiety, somatization scores, generic and disease-specific quality of life., Results: Twenty-three patients were enrolled, 10 in the intervention arm and 13 controls. Mean fatigue severity and impact scores improved for patients in the intervention group (by 14.5-13.1 and 49.7-45.8, respectively), and worsened in controls (by 11.5-12.6 and 33.5-35 respectively). Mean Short Form 36 (SF-36) scores for role limitations due to physical health decreased from 44.4 to 38.9 in the intervention group, but increased from 44.2 to 51.9 among controls. Energy scores in the intervention group improved from 17.8 to 26.6, but only from 31.4 to 31.7 among controls. Short IBD questionnaire scores improved in both groups, from 46.2 to 45.2 in controls compared with 44.4-40 in the intervention group., Discussion: In this small pilot RCT, positive effects were demonstrated on fatigue, energy levels and other quality of life outcomes. Larger, adequately powered studies with longer follow up are required. ClincialTrials.gov identifier: NCT02709434., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: Mood may have an important role in the natural history of inflammatory bowel disease (IBD). However, the impact of antidepressant use on prognosis is unknown. We aimed to address this in a longitudinal study in a referral population., Methods: We collected demographic data, clinical disease activity and mood using validated questionnaires, and antidepressant use at baseline. Longitudinal disease activity was defined by disease flare or need for glucocorticosteroids, escalation of medical therapy, hospitalisation, or intestinal resection. We compared rates of these over a minimum period of 2 years according to antidepressant use at baseline., Results: In total, 331 patients provided complete data, of whom 54 (15.8%) were taking an antidepressant at study entry. Older age, female gender, and abnormal mood scores were associated with antidepressant use. During longitudinal follow-up, there was a trend towards lower rates of any of the four endpoints of IBD activity of interest in patients with abnormal anxiety scores at baseline and who were receiving an antidepressant (42.3% versus 64.6%, P = 0.05). Based on univariate Cox regression analysis, there was a trend towards lower rates of escalation of medical therapy among patients receiving antidepressants at baseline (hazard ratio (HR) = 0.59; 95% confidence interval (CI) 0.35-1.00, P = 0.05). None of the differences observed persisted after multivariate Cox regression., Conclusions: Antidepressants may have some beneficial effects on the natural history of IBD, but larger studies with longer follow-up are required. Whether these effects are limited to patients with abnormal mood remains uncertain.

Background: The microbiome is implicated in the pathogenesis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Whether a distinct microbiome profile is associated with the reporting of IBS-type symptoms in IBD patients is uncertain. We aimed to resolve this issue using a cross-sectional study design., Methods: Using clinical disease activity indices, the Rome III criteria for IBS and fecal calprotectin levels, we divided IBD patients into 4 groups: IBS-type symptoms, quiescent disease, occult inflammation, and active disease. A16S rRNA microbiome analysis was performed to determine whether any taxa were differentially abundant, and whether there were any differences in alpha or beta diversity in patients reporting IBS-type symptoms compared with those in the other 3 groups., Results: Of 270 patients included, 70 (25.9%) had IBS-type symptoms, 81 (30.0%) quiescent IBD, 66 (24.4%) occult inflammation, and 53 (19.6%) active IBD. At phylum level, there was a nonsignificant increase in the abundance of Actinobacteria in patients reporting IBS-type symptoms, but no other differences at any taxonomic level. When compared with patients reporting IBS-type symptoms, mean alpha diversity was greater in patients with quiescent disease, although this was nonsignificant (28.6 vs 31.7, P = 0.33), and similar to those with occult inflammation and active disease. Beta diversity variation among the 4 groups was significant for unweighted (P = 0.002) but not weighted (P = 0.21) UniFrac analysis., Conclusions: Reporting IBS-type symptoms was not associated with distinct microbiome alterations. Unmeasured confounding could have impacted the significance of our findings.

Objectives: Recently, the infliximab biosimilar (CT-P13) received market authorisation for inflammatory bowel disease (IBD), allowing cost benefits when switching to CT-P13. We aim to assess the efficacy and safety of switching from originator infliximab to CT-P13 for new and existing patients., Material and Methods: Treatment response, remission, primary and secondary loss of response rates, and adverse events in patients who initiated infliximab originator in the 12 months pre-switch (n = 53) were compared with the patients who initiated CT-P13 in the 12 months post-switch (n = 69). Sustained responses were compared for existing infliximab originator patients who switched to CT-P13 (n = 191) and those who continued with the originator (n = 19)., Results: There was no difference in remission (58.1% vs. 47.4%, p = .37), response (12.6% vs. 10.5%, p = .80), secondary loss of response (24.6% vs. 42.1%, p = .10), or adverse events (4.7% vs. 0% p = 1.0) between those who switched to CT-P13 and those who continued infliximab originator. There was no difference in remission (42.0% vs. 26.4%, p = .074), response (21.7% vs. 22.6%, p = .91), primary non-response (5.8% vs. 15.1%, p = .09), secondary loss of response (21.7% vs. 22.6%, p = .91), or adverse events (8.7% vs. 11.3%, p = .63) in those who initiated CT-P13 compared with infliximab originator., Conclusions: There was no difference in the efficacy and safety of infliximab originator and CT-P13 during the first 12 months after switching.

Objectives: The impact of irritable bowel syndrome (IBS)-type symptoms on the natural history of inflammatory bowel disease (IBD) is uncertain. We aimed to address this in a longitudinal study of secondary care patients., Methods: Longitudinal disease activity was defined by disease flare, escalation of medical therapy, hospitalization, or intestinal resection. The number of investigations performed and clinics attended determined healthcare utilization. Psychological well-being and quality of life were assessed using validated questionnaires. These outcomes were compared over a minimum period of 2 years between patients reporting IBS-type symptoms and patients with quiescent disease, occult inflammation, and active disease at baseline., Results: In 360 IBD patients, there were no differences in longitudinal disease activity between patients with IBS-type symptoms and patients with quiescent disease or occult inflammation. Disease flare and escalation of medical therapy was more common in patients with active disease than in patients with IBS-type symptoms (hazard ratio (HR) = 3.16; 95% confidence interval (CI) 1.93-5.19 and HR = 3.24; 95% CI 1.98-5.31, respectively). A greater number of investigations were performed in patients with IBS-type symptoms than quiescent disease (P = 0.008), but not compared with patients with occult inflammation or active disease. Anxiety, depression, and somatization scores at follow up were higher, and quality-of-life scores lower, in patients with IBS-type symptoms when compared with patients with quiescent disease, but were similar to patients with active disease., Conclusions: IBS-type symptoms in IBD were associated with increased healthcare utilization, psychological comorbidity, reduced quality of life, but not adverse disease activity outcomes during extended follow-up.