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The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a \"treat-to-target\" clinical management strategy using an evidence-based expert consensus process. A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

This third section of the European Crohn’s and Colitis Organisation (ECCO) Consensus on the management of Crohn’s disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn’s disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn’s disease.

Background and aims: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality. Material and methods: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality. Results: Fifty six of 314 Crohn’s disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9–1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6–1.0)). Eighteen patients with Crohn’s disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn’s disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2–11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7–10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3–7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4–0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn’s disease, a diagnosis after 1980 was associated with decreased mortality. Conclusions: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn’s disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.

Background: No previous correlation between phenotype at diagnosis of Crohn’s disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Methods: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Results: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30–2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10–3.14)) and males (SMR 1.79 (95% CI 1.11–2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32–3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80–2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. Conclusions: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

BackgroundIBDs are chronic destructive disorders that negatively affect the functional status of patients. Recently, the Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to standard WHO processes. The aims of the current study were to validate the IBD-DI in an independent patient cohort, to develop an index-specific scoring system and to describe the disability status of a well-defined population-based cohort of French patients with IBD.MethodsFrom February 2012 to March 2014, the IBD-DI questionnaire was administered to a random sample of adult patients with an established diagnosis of IBD issued from a French population-based registry. The IBD-DI consists of 28 items that evaluate the four domains of body functions, activity participation, body structures and environmental factors. Validation included item reduction and data structure, construct validity, internal consistency, interobserver and intraobserver reliability evaluations.Results150 patients with Crohn's disease (CD) and 50 patients with UC completed the IBD-DI validation phase. The intraclass correlation coefficient for interobserver reliability was 0.91 and 0.54 for intraobserver reliability. Cronbach's α of internal consistency was 0.86. IBD-DI scores varied from 0 to 100 with a mean of 35.3 (Q1=19.6; Q3=51.8). IBD-DI scores were highly correlated with Inflammatory Bowel Disease Questionnaire (−0.82; p<0.001) and SF-36 (–0.61; p<0.05) scores. Female gender (p<0.001), clinical disease activity (p<0.0001) and disease duration (p=0.02) were associated with higher IBD-DI scores.ConclusionsThe IBD-DI has been validated for use in clinical trials and epidemiological studies. The IBD-DI showed high internal consistency, interobserver reliability and construct validity, and a moderate intraobserver reliability. It comprises 14 questions and ranges from 0 to 100. The mean IBD-DI score was 35.3 and was associated with gender, clinical disease activity and disease duration. Further research is needed to confirm the structural validity and to assess the responsiveness of IBD-DI.Trial registration number2011-A00877-34

To evaluate the impact of eHealth on disease activity, the need for hospital contacts, and medical adherence in children and adolescents with inflammatory bowel disease (IBD). Furthermore, to assess eHealth's influence on school attendance and quality of life (QoL).MethodsPatients with IBD, 10 to 17 years attending a public university hospital, were prospectively randomized to a 2-year open label case-controlled eHealth intervention. The eHealth-group used the web-application www.young.constant-care.com (YCC) on a monthly basis and in case of flare-ups, and were seen at one annual preplanned outpatient visit. The control-group continued standard visits every third month. Every 3 months, both groups had blood and fecal calprotectin tested and the following were assessed: escalation in medication, disease activity, hospital contacts, medical adherence, school absence, and QoL.ResultsFifty-three patients in nonbiological treatment were included (27 eHealth/26 control). We found no differences between the groups regarding escalation in treatment and disease activity (symptoms, fecal calprotectin, and blood). The number of total outpatient visits (mean: eHealth 3.26, SEM 0.51; control 7.31, SEM 0.69; P < 0.0001) and IBD-related school absence (mean days: eHealth 1.6, SEM 0.5; control 16.5, SEM 4.4; P < 0.002) was significantly lower in the eHealth-group. No differences in medical adherence and QoL were found. Adherence to YCC was 81% (384 of the 475 expected entries). None of the patients or parents felt unsafe using the eHealth system.ConclusionsThe use of eHealth in children and adolescents with IBD is feasible, does not lead to impaired disease control, and can be managed by the patients without risk of increased disease activity.

The risk of intestinal malignancy in Crohn's disease (CD) remains uncertain since risk estimates vary worldwide. The global CD population is growing and there is a demand for better knowledge of prognosis of this disease. Hence, the aim of the present study was to conduct a meta-analysis of population-based data on intestinal cancer risk in CD. The MEDLINE search engine and abstracts from international conferences were searched for the relevant literature by use of explicit search criteria. All papers fulfilling the strict inclusion criteria were scrutinized for data on population size, time of follow-up, and observed to expected cancer rates. STATA meta-analysis software was used to perform overall pooled risk estimates (standardized incidence ratio (SIR), observed/expected) and meta-regression analyses of the influence of specific variables on SIR. Six papers fulfilled the inclusion criteria and reported SIRs of colorectal cancer (CRC) in CD varying from 0.9 to 2.2. The pooled SIR for CRC was significantly increased (SIR, 1.9; 95% CI 1.4-2.5), as was the risk for colon cancer separately (SIR, 2.5; 95% CI 1.7-3.5). Regarding small bowel cancer, five studies reported SIRs ranging from 3.4 to 66.7, and the overall pooled estimate was 27.1 (95% CI 14.9-49.2). The present meta-analysis of intestinal cancer risk in CD, based on population-based studies only, revealed an overall increased risk of both CRC and small bowel cancer among patients with CD. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients' microbiota. Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was -126.50 (IQR -196.75 to -76.75) and for VSL#3 it was -130.00 (IQR -211.00 to -70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients' microbiota. The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622.

BackgroundThe natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities' focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients' education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial ‘Constant-care’ was undertaken in Denmark and Ireland.Methods333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs.Results88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group.ConclusionThe new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.

Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists. Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.