Introduction Crohn’s disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis.Methods and analysis We describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis.Ethics and dissemination This study protocol achieved National Health Service Research Ethics Committee (NHS REC), London—Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications.Trial registration number ISRCTN76899103.

SummaryBackgroundThe long‐term natural history and impact of irritable bowel syndrome (IBS)‐type symptoms on outcomes in inflammatory bowel disease (IBD) are uncertain.AimTo assess this in a longitudinal follow‐up study of patients in secondary careMethodsWe 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.ResultsAmong 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.ConclusionsIBS‐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.

Background: Primary care faecal calprotectin (FC) was introduced in Leeds in 2014 to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome and with the hope that it may reduce time to IBD diagnosis and treatment. This study examines the association of FC with referral routes, time to diagnosis, and time to treatment. Methods: All patients newly referred to IBD clinics in 2013 and 2016 were studied. Data on referral routes and dates, FC, date of first treatment, and proxy outcomes for disease severity were collected. Results: In 248 patients, there were no differences between 2013 and 2016 cohorts regarding baseline data and disease severity. The number of direct referrals to gastroenterology rose from 3% (2013) to 17% (2016), whilst 10% were diagnosed during emergency admissions. Referrals via suspected cancer pathways remained high (38% in 2013, 28% in 2016), whilst many had initial investigations at independent centres (16% in 2013, 24% in 2016). Time from referral to diagnosis was similar between 2013 (0.77 month) and 2016 (1.10 months, p = 0.2). A total of 48 (33.3%) patients had FC checked prior to referral, and 37.5% of these were referred directly to gastroenterology. Time from diagnosis to treatment reduced from 1.37 months (2013) to 0.72 month (2016, p = 0.01). Conclusion: Patients present via a multitude of referral pathways, but FC was associated with increased direct referrals to gastroenterology. We found a variation in time to diagnosis and treatment depending on referral routes. Further work is required to ensure patients with suspected IBD get referred to IBD services in a timely manner.

Taylor, S.A. and Mallett, S. and Bhatnagar, G. and Baldwin-Cleland, R. and Bloom, S. and Gupta, A. and Hamlin, P.J. and Hart, A.L. and Higginson, A. and Jacobs, I. and McCartney, S. and Miles, Anne and Murray, C.D. and Plumb, A.A. and Pollok, R.C. and Punwani, S. and Quinn, L. and RodriguezJusto, M. and Shabir, Z. and Slater, A. and Tolan, D. and Travis, S. and Windsor, A. and Wylie, P. and Zealley, I. and Halligan, S. (2018) Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn’s disease (METRIC): a multicentre trial. The Lancet Gastroenterology & Hepatology , ISSN 2468-1253.

Background and Aims Surgery is an important treatment for Crohn's disease [CD], but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent post-operative recurrence has been studied in previous meta-analyses, but a number of randomized controlled trials [RCTs] have recently been published. We therefore performed an updated systematic review and network meta-analysis to investigate this issue. Methods We performed a comprehensive literature search through to July 2018 to identify RCTs investigating the endoscopic and clinical recurrence of CD at 12 months post-operatively. We performed a random-effects network meta-analysis to produce a pooled relative risk [RR] with 95% confidence intervals [CIs]. We ranked the treatments according to their P-score. Results We included 10 RCTs, containing 751 patients, in our primary analysis of endoscopic recurrence of CD at 12 months. Anti-tumour necrosis factor [TNF]- therapies were significantly better than placebo, either alone [P-score 0.98, RR 0.13; 95% CI 0.04-0.39] or in combination with 5-aminosalicylates [5-ASAs] [P-score 0.81, RR 0.30; 95% CI 0.12-0.75], or 5-nitroimidazoles [P-score 0.75, RR 0.40; 95% CI 0.23-0.69]. Combination therapy with a thiopurine and 5-nitroimidazole was also more effective than placebo [P-score 0.59, RR 0.56; 95% CI 0.40-0.80], as was thiopurine monotherapy [P-score 0.31, RR 0.84; 95% CI 0.74-0.94]. However, neither 5-nitroimidazoles nor 5-ASAs alone were superior to placebo. Conclusions In network meta-analysis, anti-TNF- therapies alone, or in combination, appear to be the best medications for preventing endoscopic post-operative recurrence of CD.

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.

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.

Background: Inflammatory bowel disease (IBD) related arthropathy may manifest as peripheral arthritis, dactylitis or enthesitis as well as inflammatory back pain (IBP) due to sacroiliac joint (SIJ) and/or spinal inflammation. HLA-B27 correlates with the presence of MRI determined SIJ bone marrow oedema (BMO) in axial spondyloarthritis (axSpA) and axial psoriatic arthritis (PsA) patients. The prevalence of HLA-B27 positivity is low in IBD and patients may already be on therapy that potentially modifies MRI spinal lesions at the time of imaging. Objectives: To evaluate the utility of MRI to aid the diagnosis of axSpA in IBD patients with IBP and to explore the relationship of MRI abnormalities with HLA-B27 status. Methods: Cross-sectional, retrospective audit of consecutive MRI scans of the SIJ and spine performed (2008-2018) in a large teaching hospital. All scans were requested in IBD patients presenting with IBP and clinical suspicion of axSpA. Demographic and clinical data were retrieved from the medical notes. Decision from the clinician whether the patient had axSpA related to the IBD was also recorded. MRI scans were scored by 2 readers using the semiquantitative Leeds Scoring System (BMO grade from 0 to 3)1. An overall score for inflammatory (sum of SIJ and Spine BMO scores) and structural lesions (sum of lesions per quadrant) was calculated. Results: MRI scans from 119 IBD (Crohn’s n=82, ulcerative colitis n=31, and undifferentiated IBD n=6) patients were available for analysis. 63.9% were female, mean age 38.7 years at time of MRI with mean age of IBP onset 36.3 years. The majority (n=65/83, 78.3%) were HLA-B27 negative (missing data n=36). Thirty subjects were receiving biologic therapy for IBD. A summary of MRI findings (SIJ and spine) is shown on Table 1.Abstract aB0727 Table 1 Abnormal SIJ MRI BMO Grade 1 N=20 (16.8%) Grade 2 N=24 (20.2%) Structural lesions Fat deposition N=46 (38.7%) Sclerosis N=45 (37.8%) Erosions N=39 (32.8%) Ankylosis N=4 (3.4%) Abnormal Spine MRI BMO <3 lesions N=17 (14.3%) 3 lesions N =7 (5.9%)(ASAS criteria) Structural lesions Posterior fusion N=1 (1%)Syndesmophytes N=1 (1%) Degenerative disc disease was common in the cohort with 55/119 having at least one affected level. Other incidental findings included: hemangiomas (n=8), osteoporotic fractures (n=2) and myeloma (n=1). The total BMO MRI scores (Spine plus SIJ), SIJ only BMO score, erosions, sclerosis and fat scores were higher in the HLA-B27 positive group as seen in Figure 1, with only differences in the erosion (P=0.002) and sclerosis score (P=0.038) being statistically significant.Abstract aB0727 Figure 1 Less active (BMO) and structural lesions were seen in the biologic treated group, reaching statistical significance in total BMO (P=0.041), erosions (P=0.039), fat (P=0.003) and sclerosis (P=0.013) scores. A clinical diagnosis of axial SpA was made in 42/119 (35%) cases. Of these, n=25/42 had BMO (SIJ or spine) and structural lesions. Structural lesions alone were evident in 13/42 of these cases. BMO lesions alone with no structural changes was found in 2 cases (grade 1). Conclusion: MRI findings of sacroiliitis and spinal involvement, defined as a combination of active and structural lesions, are common in IBD subjects with symptomatic back pain. The low prevalence of BMO seen in this cohort may represent partially treated disease. The addition of structural lesions to the current definitions of a positive MRI, may help with the diagnosis of axSpA. The presence of HLA-B27 positivity appears to define a more severe axial phenotype in IBD associated axSpA. References [1] Marzo-Ortega H, et al. Ann Rheum Dis2009; 68:1721–7. Disclosure of interests: Xabier Michelena-Vegas: None declared, Leticia Garcia-Montoya: None declared, Gabriele De Marco: None declared, Dennis McGonagle Consultant for: Lilly, Novartis UCB, Speakers bureau: Lilly, Novartis UCB, John Hamlin: None declared, Christian Selinger: None declared, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: abbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: abbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB

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: 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.

BACKGROUND & AIMS Inflammatory bowel diseases (IBD) are associated with mood disorders, such as anxiety or depression, but it is not clear whether one contributes to development of the other, or if the interaction is bi-directional (anxiety or depression contributes to the progression of IBD, and IBD affects psychological health). We performed a 2-year longitudinal prospective study of patients in secondary to care investigate the bi-directionality of IBD and mood disorders. METHODS We collected data from 405 adult patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) from November 2012 through June 2017. Demographic features, subtypes of IBD, treatments, symptoms, somatization, and fecal level of calprotectin were recorded at baseline. IBD activity was determined at baseline and after the follow-up period (2 years or more) using the Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for UC (scores ≥5 used to define disease activity). Anxiety and depression data were collected using the Hospital Anxiety and Depression Scale (HADS), at baseline and after the follow-up period. Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalization secondary to IBD activity, and intestinal resection during follow-up were assessed via case note review. A brain-gut direction of disease activity was defined as development of new IBD activity in patients with quiescent IBD and abnormal HADS scores at baseline. A gut-brain direction of disease activity was defined by subsequent development of abnormal HADS scores in patients with active IBD and normal HADS scores at baseline. We performed multivariate Cox regression controlling for patient characteristics and follow-up duration. RESULTS Baseline CD or UC disease activity were associated with an almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio [HR], 5.77; 95% CI, 1.89-17.7). In patients with quiescent IBD at baseline, baseline abnormal anxiety scores were associated with later need for glucocorticosteroid prescription or flare of IBD activity (HR, 2.08; 95% CI, 1.31-3.30) and escalation of therapy (HR, 1.82; 95% CI, 1.19-2.80). These associations persisted when normal IBD activity index scores and fecal level of calprotectin <250 μg/g were used to define quiescent disease at baseline. CONCLUSIONS In a 2-year study of patients with CD or UC, we found evidence for bi-directional effects of IBD activity and psychological disorders. Patients with IBD should be monitored for psychological well-being.

Background Vedolizumab (VDZ) is a gut selective α4β7 anti-integrin approved for the treatment of UC and CD. We aimed to assess one year clinical and safety outcomes of VDZ. Methods We previously reported 12 week outcomes using retrospectively collected demographic, clinical, and adverse effects data of patients treated with VDZ at 8 UK centres since 2014. We now report longer term outcomes, evaluating clinical response at week 12 and 52, using Physician Global Assessment, Harvey Bradshaw Index (HBI) and partial Mayo Score (pMS). Results Of 203 patients, 135 had CD (96% anti-TNF experienced), and 68 UC (66% anti-TNF experienced). 101 received concomitant immunomodulator therapy and 97 received steroid bridging therapy. Of 135 CD patients, 9 discontinued VDZ prior to week 12. At week 12, 38.5% were in PGA remission and 40.0% had a PGA response. Between week 12 and 52, a further 35 patients discontinued VDZ. At week 52 PGA remission and response were seen in 39.2% and 24.3% respectively. Mean HBI decreased from 9.2 (baseline) to 5.1 (week 12) and 5.2 at week 52 (p<0.01). Of 68 UC patients, 3 discontinued VDZ prior to week 12. At week 12, 48.5% were in PGA remission and 42.6% had a PGA response. Between week 12 and 52, a further 9 patients discontinued VDZ. At week 52, PGA remission and response were seen in 67.2% and 16.4% respectively. Mean pMS decreased from 6.1 (baseline) to 3.1 (week 12) and 2.2 (week 52; p<0.01). Adverse events were reported in 48 cases (24%) Of these 29 were infection related. Overall incidence of infection was 11.1 per 100 person-years of VDZ exposure. Conclusion In our cohort of refractory (predominantly anti-TNF experienced) patients, VDZ proved to be safe and effective. Although at 12 weeks response/remission rates were similar in CD and UC, VDZ appeared to be more effective at maintaining remission for UC compared to CD. The incidence of infectious complications was lower than that seen with anti-TNF therapies (average 14 per 100 person-years).

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: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

Introduction We have previously shown that therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies (ADAS) can aid decision making for patients on biological therapy, in conjunction with clinical symptoms, disease history and investigations. The aims of this follow-up study were to evaluate 1 year outcomes of patients who had decisions changed on the basis of TDM results in our original study, and to test the hypothesis that TDM-based decisions to alter or stop IFX treatment are safe and durable. Methods In our original study, a blinded treatment decision was first made, without knowledge of IFX trough and ADAs. Immediately after this, TDM results were released and a final treatment decision was recorded. For this study we collected long-term clinical outcomes 12 months after the decision. We compared patients with changed treatment decisions with those where the decision to continue IFX remained unchanged. We defined changed decision groups as (I) IFX stopped, (II) switch to other biological therapy, and (III) continue IFX with adjusted dose or interval. Events of interest were hospitalisation for IBD or further changes to biological therapy. Results Of 190 patients reviewed in virtual biologics clinic 54 (28%) had decisions changed in the light of results of TDM. Of the 136 patients with an unchanged decision, 128 who continued IFX as previously dosed were used as the comparator group. There were no differences in hospitalisation rates between 3 changed decision groups (I, p=1), (II, p=0.2), (III, p=0.4) and the unchanged decision comparator group (table 1). Similarly, we found no differences in subsequent biologic therapy switches between 3 changed decision groups (I, p=1), (II, p=1), (III, p=0.2) and the unchanged decision comparator group. Conclusion Our study demonstrates that changes to IFX treatment based on TDM were durable. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes with those who continued IFX therapy unchanged. TDM-based decisions about IFX treatment that incorporate the clinical picture can safely alter therapy without exposing patients to an increased risk of hospitalisation or need for subsequent changes to biologic therapy.

BACKGROUND:Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. METHODS:We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. FINDINGS:284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. INTERPRETATION:Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. FUNDING:National Institute of Health and Research Health Technology Assessment.

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 & AIMS: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with inflammatory bowel disease (IBD), but it is unclear whether this relates to occult IBD activity. We attempted to resolve this issue in a secondary care population by using a cross-sectional study design.METHODS: We analyzed Rome III IBS symptoms, disease activity indices, and psychological, somatization, and quality of life data from 378 consecutive, unselected adult patients with IBD seen in clinics at St James's University Hospital in Leeds, United Kingdom from November 2012 through June 2015. Participants provided a stool sample for fecal calprotectin (FC) analysis; levels >= 250 mu g/g were used to define mucosal inflammation. By using symptom data and FC levels we identified 4 distinct groups of patients: those with true IBS-type symptoms (IBS-type symptoms with FC levels <250 mu g/g, regardless of disease activity indices), quiescent IBD (no IBS-type symptoms with FC levels <250 mu g/g, regardless of disease activity indices), occult inflammation (normal disease activity indices and FC levels >= 250 mu g/g, regardless of IBS symptom status), or active IBD (abnormal disease activity indices with FC levels >= 250 mg/g, regardless of IBS symptom status). We compared characteristics between these groups.RESULTS: Fifty-seven of 206 patients with Crohn's disease (27.7%) and 34 of 172 patients with ulcerative colitis (19.8%) had true IBS-type symptoms. Levels of psychological comorbidity and somatization were significantly higher among patients with true IBS-type symptoms than patients with quiescent IBD or occult inflammation. Quality of life levels were also significantly reduced compared with patients with quiescent disease or occult inflammation and were similar to those of patients with active IBD. By using FC levels >= 100 mu g/g to define mucosal inflammation, we found a similar effect of IBS-type symptoms on psychological health and quality of life.CONCLUSIONS: In a cross-sectional study, we identified a distinct group of patients with IBD and genuine IBS-type symptoms in the absence of mucosal inflammation. These symptoms had negative effects on psychological well-being and quality of life to the same degree as active IBD. New management strategies are required for this patient group.

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.