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Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times. Funding Agencies|Akershus University Hospital

Tumour necrosis factor-α (TNF) antagonists have improved the management of inflammatory bowel disease (IBD), however, their usage and administration persist to be suboptimal. Here, we examined the relationship between tissue-specific TNF mRNA expression in mucosal biopsies from IBD patients and anti-TNF treatment response. Archived tissue samples from patients with luminal IBD that had all been or were in treatment with anti-TNF were included (18 adults and 24 paediatric patients). Patients were stratified into three groups according to anti-TNF response: responders, primary non-responders (PNR) and secondary loss of response (SLOR). TNF mRNA was detected using RNAscope in situ hybridisation (ISH) and the expression was quantified using image analysis. The ISH analysis showed varying occurrence of TNF mRNA positive cells located in lamina propria and often with increased density in lymphoid follicles (LF). Consequently, expression estimates were obtained in whole tissue areas with and without LF. Significantly higher TNF mRNA expression levels were measured in adults compared to paediatric patients in both the analyses with and without LF (p = .015 and p = .016, respectively). Considering the relation to response, the adult and paediatric patients were evaluated separately. In adults, the TNF expression estimates were higher in PNRs compared to responders with and without LF (p = .017 and p = .024, respectively). Our data indicate that adult PNR have significantly higher TNF mRNA levels than responders. This suggests that higher anti-TNF dose may be considered for IBD patients with high TNF mRNA expression estimates from the start of treatment.

Background Few population-based studies have investigated the long-term prognosis of Crohn's disease (CD). Aim To determine the long-term natural disease course of CD with regard to surgery, cancer and mortality in a population-based cohort followed for more than 50 years. Methods All patients diagnosed with CD from 1962 to 1987 in Copenhagen County, Denmark were included in a population-based cohort. Information about surgeries, cancers and mortality was collected from patient files from 1962 to 1987 and from the Danish National Patient Registry, Cancer Registry, and from the Register of Causes of Death, 1987-2017. Patients were matched with individuals from the general population. Results A total of 373 patients were followed for a median of 33 years (range: 0-56 years). The cumulative probability of surgery 10, 20, 30, 40 and 50 years after diagnosis was 62% (CI 95%: 57%-67%), 71% (CI 95%: 66%-75%), 72% (CI 95%: 67%-76%), 74% (CI 95%: 69%-79%) and 74% (CI 95%: 69%-79%), respectively. A total of 142 patients (54%) were operated upon at least twice: 69 (26%) needing two surgeries and 73 (28%) needing three or more. Patients with CD were found to be at increased risk of intestinal (small bowel, rectum and anus) and extra-intestinal (respiratory organs and skin) cancer. All-cause mortality among CD patients was higher than among controls (RR: 1.22, CI 95%: 1.04-1.43), whereas mortality due to gastrointestinal cancer was not. Conclusion After 50 years of follow-up, 75% CD patients had undergone surgery, with most needing repeat surgery. The risk of intestinal and extra-intestinal cancers, as well as mortality, was higher among CD patients than the background population.

Background and Aims Few studies have assessed the contemporary patterns of disease activity in patients with inflammatory bowel disease [IBD]. We aimed to describe the disease patterns and their long-term outcomes. Methods All Danish individuals with IBD between 1995 and 2018 were identified using information about IBD-related hospitalizations, surgeries and redeemed prescriptions. The disease activity patterns for 5- and 10-year periods were assessed. Results In incident patients with Crohn’s disease [CD], severe disease activity occurred in the year of diagnosis in 80% of patients; for ulcerative colitis [UC] this figure was 75%, in addition to 3.4% of UC patients who underwent a colectomy within the first year. After 20 years of disease, the proportion of CD and UC patients in remission increased to 89% and 72%, respectively. The proportion of prevalent patients in remission each year was stable, despite the introduction of biological therapies. A decreasing activity pattern was the most common in both CD and UC patients [both 45%]. The distribution of the disease activity patterns was seen to be stable over time. A quiescent disease pattern was accompanied by a significantly higher risk of intestinal cancer [HR: 3.37, 95% CI: 1.23–9.19] for CD patients, according to a Cox proportional hazards model. In UC patients, increasing disease activity [HR: 0.67, 95% CI: 0.31–1.48] was associated with an increased risk of intestinal cancer. Conclusions We report the distribution of disease patterns among IBD patients. Patients with quiescent CD, as well as UC patients with chronic continuous or increasing activity, were at increased risk of developing intestinal cancer.

OBJECTIVE: Changes in the secretion of gut-derived peptide hormones have been associated with the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. In this study, the effects of RYGB on anthropometrics, postprandial plasma hormone responses, and mRNA expression in small intestinal mucosa biopsy specimens before and after RYGB were evaluated.METHODS: In a cross-sectional study, 20 individuals with obesity undergoing RYGB underwent mixed meal tests and upper enteroscopy with retrieval of small intestinal mucosa biopsy specimens 3 months before and after surgery. Concentrations of circulating gut and pancreatic hormones during mixed meal tests as well as full mRNA sequencing of biopsy specimens were evaluated.RESULTS: RYGB-induced improvements of body weight and composition, insulin resistance, and circulating cholesterols were accompanied by significant changes in postprandial plasma responses of pancreatic and gut hormones. Global gene expression analysis of biopsy specimens identified 2,437 differentially expressed genes after RYGB, including changes in genes that encode prohormones and G protein-coupled receptors.CONCLUSIONS: RYGB affects the transcription of a wide range of genes, indicating that the observed beneficial metabolic effects of RYGB may rely on a changed expression of several genes in the gut. RYGB-induced changes in the expression of genes encoding signaling peptides and G protein-coupled receptors may disclose new gut-derived treatment targets against obesity and diabetes.

Bile acid diarrhoea is an underdiagnosed disease estimated to affect 1-2% of the general population. Case reports indicate that the glucagon-like peptide 1 receptor agonist liraglutide might be an effective treatment for bile acid diarrhoea. We aimed to investigate the safety and efficacy of liraglutide for the treatment of bile acid diarrhoea.We conducted a randomised, double-blind, active-comparator, double-dummy, non-inferiority clinical trial at the Center for Clinical Metabolic Research at Copenhagen University Hospital-Herlev and Gentofte, Hellerup, Denmark. Patients aged 18-75 years withBetween April 1, 2019, and Jan 31, 2021, 52 patients were enrolled; 26 were assigned to liraglutide and 26 to colesevelam. 20 (77%) of 26 participants on liraglutide and 13 (50%) of 26 on colesevelam experienced a 25% or greater reduction in stool frequency, corresponding to a significant risk difference of -27% in favour of liraglutide (one-sided 95% CI -100 to -6). Liraglutide was therefore superior to colesevelam in reducing daily stool frequency. Mild nausea with a duration of 10-21 days was reported by six participants in the liraglutide group and by one participant in the colesevelam group. No other adverse events were reported.The superiority of liraglutide compared with colesevelam in reducing stool frequency suggests consideration of liraglutide as a potential new treatment modality for bile acid diarrhoea, although larger confirmatory trials powered for superiority are warranted.Novo Nordisk, Novo Nordisk Foundation, Foundation for the Advancement of Medical Science under The A.P. Møller and Chastine Mc-Kinney Møller Foundation.

INTRODUCTION Differential diagnosis of Inflammatory Bowel Disease Unclassified (IBDU) patients to Crohn’s Disease (CD) or Ulcerative Colitis (UC) at diagnosis is challenging. Personalized disease-specific strategies are becoming state of art and therefore it is of importance for outcome of the patients and treatment decision to be taken by the clinicians to have a precise diagnosis. METHODS Whole transcriptome RNA sequencing was performed using AmpliSeq human gene expression panel on formalin-fixed paraffin-embedded (FFPE) colonic mucosal biopsies of IBD patients (CD, n=16, UC, n=17) and non-IBD controls (n=10) to study differential gene expression between CD and UC samples. Top 100 of the most significant differentially expressed genes were then tested in two independent external GEO datasets. Functional enrichment analysis of 10 successful candidates were performed and 7 genes were selected for further validation. RT-qPCR analyses were performed on an independent patient cohort of 45 CDs and 53 UCs along with 12 non-IBD controls. The cDNA samples were submitted to quality restriction during the statistical analysis resulting in a cut-off of Ct values below 29 for the endogenous control allowing 46 patient samples to enter the analysis. In situ hybridization (ISH) was performed using RNAscope on 11 selected cases for describing tissue localisation and expression. RESULTS Sequencing results showed 308 genes differentially expressed between CD and UC from a total of 14190 genes. The genes MTCL1, SH3PXD2A-AS1, CLCF1, and CD180 were under the limit of detection with RT-qPCR and were excluded from further analysis. Relative expression levels from RT-qPCR for the genes PI3, ANXA1, and VDR, together with the age and sex, resulted in an area under the receiver-operating characteristic curve (AUC) of 0.84 (P = 0.02) in discriminating CD from UC. Significantly higher expression of VDR alone was observed in CD samples with AUCs of 0.77 (P = 0.01). ISH analyses showed expression of PI3, ANXA1, and VDR mRNAs localized to mucosal epithelial cells. CONCLUSION Using whole transcriptome analysis of FFPE sample-derived RNA, we have identified genes that are differentially expressed in CD and UC, and we have developed an RT-qPCR assay including a panel of 3 genes (PI3, ANXA1, VDR) for the differential diagnosis among IBD unclassified (IBDU) patients. We propose that the RT-qPCR assay could be used in a clinical routine setup for distinguishing UC from CD.

Context After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1). Objective To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. Design and Setting Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. Participants Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. Interventions Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB. Main Outcome Measures The 29–amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry–validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry. Results Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon. Conclusion Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

Background Long-term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited. Aims To determine the long-term course and prognosis of UC, including patients' risks of surgery, cancer and mortality, in a population-based cohort followed for over 50 years METHODS: All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population-based cohort. We extracted information about IBD-related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988-2017. Patients were matched with up to 50 individuals from the general population. Results We followed 1161 patients for a median of 34 years (range: 0.1-56.0). Median age at diagnosis was 33 years (range: 2-88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%-25%), 27% (95% CI: 25%-30%), 31% (95% CI: 28%-34%), 34% (95% CI: 31%-37%), and 40% (95% CI: 36%-44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All-cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82-0.99). Conclusion In this population-based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra-intestinal cancers. However, UC patients' risk of mortality is comparable to that of the background population.

Despite the increasing use of biologics in patients with inflammatory bowel disease (IBD), real-world data about outcomes in the era of biologics remain inconclusive.To investigate trends in surgeries, hospitalisations and medication use in patients with IBD in a multinational, population-based cohort METHODS: We included 42,894 patients with ulcerative colitis (UC) and 24,864 with Crohn's disease (CD) who were diagnosed between 2010 and 2017 in Denmark, Norway and Sweden. We extracted data about surgeries, hospitalisations and medications from national registries and compared across countries and diagnosis years.Between 2010 and 2017, 2-year surgery rates were 4-7% in UC and 10-15% in CD and were stable over time. Two-year hospitalisation rates increased in Denmark (UC: 20% to 35%; CD: 27% to 32%) but were stable in Norway and Sweden (fluctuating between 33% and 37% in UC, and 46% and 52% in CD). Two-year rates of biologic use increased in both UC (7% to 16% in Denmark, 8% to 18% in Norway) and CD (22% to 26% in Denmark; 21% to 35% in Norway). Two-year rates of immunomodulator use increased in Norway (from 14% to 23% in UC; 37% to 45% in CD) and Sweden (from 41% to 52% in CD), but were stable in Denmark (between 17% and 21% in UC; 39% to 46% in CD).Between 2010 and 2017, surgery rates among Scandinavian patients with IBD remained stable, with no clear changes in hospitalisation rates despite the increasing use of immunomodulators and biologics.

Bile acid malabsorption (BAM) is caused by excessive spill-over of bile acids to the colon and is estimated to affect ∼1% of the general population. It is a socially debilitating disease with watery diarrhea and high stool frequency as main symptoms. BAM is diagnosed by the 75selenium homotaurocholic acid test (SeHCAT) measuring the retention of bile acids. Bile acid sequestrant (BAS) treatment, which is the only recommended treatment of BAM, is associated with poor effect and low compliance. Case reports suggest that the glucagon-like peptide 1 receptor analog (GLP-1RA) liraglutide may be an effective treatment of BAM. In this double-blind, double-dummy, non-inferiority study, nondiabetic individuals with SeHCAT-verified BAM, age 18-75 years and BMI 18.5-40 kg/m2 were randomized to receive the GLP-1RA liraglutide (uptitrated to 1.8 mg per day) or the BAS colesevelam (1.875 mg × 2 per day) for 6 weeks prior to a 7-day run-in period without treatment. SeHCAT was made at baseline, week 3 and week 6. The primary outcome was the proportion of patients experiencing a reduction in stool frequency of ≥25% per day. Of 52 randomized subjects (18 males, 34 females, mean age 50.2 years and BMI 29.9 kg/m2), one patient from each group dropped out due to gastrointestinal side effects. At end-of-treatment, 20 (77%) individuals on liraglutide had experienced a reduction in stool frequency of ≥25% per day vs. 13 (50%) on colesevelam treatment, corresponding to a statistically superior risk difference of -0.27 (one-sided 95% CI: -1; -0.06). In contrast to the colesevelam-treated group, the liraglutide-treated group exhibited a significant increase in SeHCAT values resulting in significantly higher values at end-of-treatment (mean (SD) 8.9 (7.3) vs. 0.9 (2.0) %, P In conclusion, we show that liraglutide enhances the reabsorption of bile acids and constitutes a safe and effective treatment of BAM which is superior compared to current standard of care (colesevelam). Disclosure M. L. Kårhus: None. A. Brønden: None. J. Forman: None. A. Haaber: None. E. Langholz: None. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. D. P. Sonne: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. Funding Novo Nordisk Foundation (NNF17OC0029710); A.P. Møller and Chastine Mc-Kinney Møller Foundation (19-L-0002)

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity of the disease often delays the diagnosis and the initiation of appropriate treatments. In a subset of patients, IBD leads to colitis-associated cancer (CAC). MicroRNAs are single-stranded regulatory noncoding RNAs of 18 to 22 nucleotides with putative roles in the pathogenesis of IBD and colorectal cancer. They have been explored as biomarkers and therapeutic targets. Both tissue-derived and circulating microRNAs have emerged as promising biomarkers in the differential diagnosis and in the prognosis of disease severity of IBD as well as predictive biomarkers in drug resistance. In addition, knowledge of the cellular localization of differentially expressed microRNAs is a prerequisite for deciphering the biological role of these important epigenetic regulators and the cellular localization may even contribute to an alternative repertoire of biomarkers. In this review, we discuss findings based on RT-qPCR, microarray profiling, next generation sequencing and in situ hybridization of microRNA biomarkers identified in the circulation and in tissue biopsies.

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery.FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (pINTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease.FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

International audience; It is increasingly admitted that Crohn's disease and ulcerative colitis, the two entities of inflammatory bowel disease, are initiated and reactivated by environmental factors in genetically susceptible hosts, and result from aberrant immune response to specific intestinal microbes, in the context of altered composition of intestinal microbiota, called dysbiosis. We hypothesize that the role of the gut microbiota in Crohn's disease pathogenesis is linked to early-life abnormal crosstalk with the host immune system under construction. By contrast, in ulcerative colitis, the detrimental effect of intestinal dysbiosis could occur at any time of life, due to instant environment. This hypothesis could explain why the incidence of Crohn's disease raises many years later than that of ulcerative colitis in developing countries that adopt the Western lifestyle. This would also explain why many early-life events, such as caesarean section, increased hygiene and repeated antibiotic exposure, are risk factors for subsequent development of Crohn's disease, but not ulcerative colitis.

Aims The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. Material and methods A total of 10 normal glucose-tolerant (NGT) obese subjects and 9 age-, body weight- and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and 1 week (1w) and 26 weeks (26w) after implantation. Results At 26w, both groups had achieved a weight loss of 6 to 7 kg. Postprandial glucagon-like peptide-1 (GLP-1) and peptide YY responses increased at 1w and 26w, but only in T2D subjects. In contrast, glucose-dependent insulinotropic polypeptide responses were reduced only by DJBS in the NGT group. Postprandial glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin responses were unaffected by DJBS in both groups. Satiety and fullness sensations were stronger and food intake was reduced at 1w in NGT subjects; no changes in appetite measures or food intake were observed in the T2D group. No effect of DJBS on postprandial gallbladder emptying was observed, and gastric emptying was not delayed. Conclusions DJBS-induced weight loss was associated with only marginal changes in postprandial physiology, which may explain the absence of effect on postprandial glucose metabolism.

Background Incidence and prevalence of inflammatory bowel diseases (IBD) have been increasing for the past decades in the western world, however with an emerging trend of incidence stabilisation in recent years. There is an indication of higher IBD incidence and prevalence in northern Europe, especially in the Nordic region, compared with southern Europe. Methods This retrospective observational study collected data from the National Patient Registries and National Prescription Registries (Sweden [SWE], Norway [NOR], Denmark [DEN]) and one university hospital database (Turku, Finland [FIN]) during 2010–2017 to investigate the annual incidence and prevalence of ulcerative colitis (UC) and Crohn’s disease (CD). Patients with ≥2 ICD-10 diagnosis codes for UC (K51) or CD (K50) from 2010 or later and no K51 or K50 codes prior to 2010 were included; patients were classified according to their last code. The look-back period for SWE was until 2000, for NOR until 2008, for DEN until 1995, and for FIN until 2004. Incidence proportions highlight results through 2016, as 2017 patients had less than 1-year follow-up. Results In total, 69,876 patients were included (SWE n = 27,902, NOR n = 20,761, FIN n = 2,118, DEN n = 19,095), of which 44 367 patients were diagnosed with UC and 25,509 with CD. In 2016, the annual incidence of UC was 28 patients per 100,000 persons in NOR, 32 patients per 100,000 persons in DEN, 25 patients per 100,000 persons in SWE, and 44 patients per 100,000 in FIN. The corresponding results for the annual incidence of CD per 100,000 persons were 22 in NOR, 16 in DEN, 16 in SWE, and 21 in FIN. The prevalence per 100,000 persons of both UC and CD was the highest in DEN, followed by SWE and NOR, and lowest in FIN. Prevalence estimates increased in all four Nordic countries during 2010–2017: for UC, from 409 to 488 patients in SWE, from 256 to 428 in NOR, from 129 to 375 in FIN, and from 577 to 798 in DEN. For CD, it increased from 261 to 313 patients in SWE, from 164 to 258 in NOR, from 54 to 164 in FIN, and from 280 to 400 in DEN. Conclusion This retrospective observational study showed that during 2016, the annual incidence of UC ranged from 25–44 patients per 100,000 persons across the evaluated Nordic countries, whereas the annual incidence of CD was 16–22 patients per 100,000 persons. Prevalence of both UC and CD increased during 2010–2017 in all four countries. Estimates of UC and CD incidence and prevalence in this analysis are greater than reported in the published literature. Additional analyses are underway to further explore the impact of methodological decisions on the estimates of UC and CD annual incidence and prevalence.

Background Biological therapy has been suggested to decrease surgery and hospitalisation risk in patients diagnosed with inflammatory bowel disease (IBD). During 2010 to 2016, the use of biologics in Denmark (DEN), Sweden (SWE) and Norway (NOR) increased dramatically and the time to first biologic treatment declined.1 However, the impact of increasing use of biologics on disease outcomes remains to be shown in real-life practice. In this nationwide study in three Nordic countries, we aimed to investigate trends in surgery and hospitalisation rates in IBD patients in the biological era.1 Høivik ML et al. Time to first treatment with biologic agents for Ulcerative Colitis and Crohn’s Disease across four Nordic countries: Results from the TRINordic study, Submitted to ECCO 2020. Methods A total number of 67 758 IBD patients (42 894 patients with ulcerative colitis (UC) and 24 864 Crohn’s disease (CD) diagnosed during the period from 2010 to 2017 in DEN, NOR and SWE were included using the National Patient Registries. Patients were required to have 1-year follow-up; results are limited to patients diagnosed between 2010 and 2016, inclusive. Using the unique personal identification number, individual-level information on surgery, hospitalisation and drug treatment were extracted from the National Patient Registries and the National Prescription Registries. Disease outcomes within two years after diagnosis were compared across annual cohorts. Results During 2010 to 2016, 2-year surgery rates in CD patients showed a non-significant decline from 11.9% in 2011 to 9.5% in 2016 in SWE while remaining stable in NOR and DEN (Figure 1). No temporal pattern in surgery risk was observed for UC. The proportion of CD patients being hospitalised within two years from diagnosis declined in SWE and NOR from 52.3% and 51.0% in 2011 to 47.3% and 38.5% in 2015 (p < 0.001), respectively, while hospitalisation in UC remained stable. In contrast, 2-year hospitalisation rates in DEN increased in CD from 27.0% in 2011 to 31.5% in 2016 (p = 0.045) and similarly in UC from 20.4 to 35.0% (p < 0.001), respectively (Figure 2). Conclusion No clear pattern was seen in two-year surgery and hospitalisation rates in IBD patients during 2010 to 2017 despite a concurrent increase in biological use in all countries. However, differences in treatment practices across countries might influence these findings. The impact of increased biological use on long-term outcomes in IBD remains to be shown.

Background Real-world data on time from diagnosis to first biologic treatment is limited for ulcerative colitis (UC) and Crohn’s disease (CD) patient populations. Methods This retrospective observational study collected data from the National Patient Registries and National Prescription Registries in Sweden (data on biologic use was only available for Stockholm [STK], Norway [NOR], Denmark [DEN]) and one university hospital database (Turku, Finland [FIN]) during 2010–2017 to investigate time from diagnosis to first biologic treatment for UC and CD. Patients with ≥2 ICD-10 diagnosis codes for UC (K51) or CD (K50) from 2010 or later were included; patients were classified according to their last code. The look-back period for SWE was until 2000, for NOR until 2008, for DEN until 1995, and for FIN until 2004. Time to first biologic was defined as the period from the first UC or CD code to first biologic record. In FIN, it was only possible to investigate infliximab (IFX). Results A total of 47,568 patients were included (STK n = 5594, NOR n = 20,761, FIN n = 2118, DEN n = 19,095). Of them, 30 397 patients had UC and 17 171 CD diagnosed during 2010–2017. Time to first biologic following diagnosis of UC or CD was decreased over time. For patients diagnosed with CD in 2015, in STK, NOR, FIN, and DEN, 30%, 35%, 25%, and 26%, respectively, received a biologic within 2 years; in 2010, the proportions were less than 10%, 20%, 5%, and 22%, respectively. FIN results may be attributed to only IFX use captured in the data sources. NOR had in most cohorts the shortest time between diagnosis and first treatment with a biologic agent, e.g. 33%, 35%, 36%, 34% and 33% of patients diagnosed with CD in 2011, 2012, 2013, 2014 and 2015, respectively, received a biologic already one month after diagnosis compared with 2%, 1%, 3%, 4% and 6%, respectively, in STK, 7%, 5%, 9%, 4% and 5%, respectively, in FIN and 3%, 10%, 28%, 12% and 23%, respectively, in DEN. Fewer UC than CD patients received biologics, but the time to first biologic was shortened to the same extent (Figure 1 and 2, respectively). In NOR, FIN and DEN, the most common biologic used was IFX for UC and CD, e.g. 18%, 14% and 15%, respectively, of UC and 35%, 17% and 35%, respectively, of CD patients diagnosed in 2015 had received IFX; in STK it was IFX for UC (8% of patients diagnosed in 2015) and adalimumab for CD (20% of patients diagnosed in 2015). Conclusion This retrospective observational study of >45 000 patients with inflammatory bowel disease in four Nordic countries showed reduced time between diagnosis and first biologic from 2010 to 2017, with the shortest time between diagnosis and first biologic in Norway. IFX was most commonly used.

Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.

To evaluate the effect of colostomy on bowel function and quality of life (QoL) in individuals with spinal cord injury (SCI).Cross-sectional descriptive study.Department for Spinal Cord Injuries and Departments of Gastroenterology and Radiology, Rigshospitalet.Eighteen individuals with SCI and a colostomy performed post injury, 12 males, 6 females, 8 with tetraplegia and 10 with paraplegia. Median age at time of study was 49.9 years, years since lesion was 3-56 years, and time since colostomy was performed 0.5 to 20 years.Questionnaires and measurement of gastrointestinal transit time (GITT).Retrospective data collection from patient records, a questionnaire on bowel management pre and post colostomy, quality of life (QoL) by SF-36, and GITT.Seventy-two percent significantly reduced their use of time on bowel emptying after the colostomy. All but one reported being content with the colostomy. Thirty-nine percent reported one or more problems related to the colostomy. Seventy-five percent had a GITT within normal range for able-bodied populations. When disregarding the physical component, QoL was not significantly lower in the total study group compared to a Danish norm group, but significantly lower when compared the subgroup of persons with tetraplegia.A colostomy reduces the time necessary for bowel management. The majority of individuals with SCI and a colostomy did not perceive bowel management as being a problem. The results indicate that colostomy is a favourable option for individuals with SCI, who spend long hours on bowel management and for whom non-invasive procedures did not improve the situation enough.

The medical management of inflammatory bowel disease has changed considerably over time with wider use of immunosuppressant therapy and the introduction of biological therapy. To what extent this change of medical paradigms has influenced and modified the disease course is incompletely known. To address this issue, an extensive review of the literature has been carried out on time trends of hospitalization, surgery, infections, cancer, and mortality rates in inflammatory bowel disease [IBD] patients. Preference was given to population-based studies but, when data from these sources were limited, large cohort studies and randomised controlled trials were also considered. In general, data on hospitalisation rates are strikingly heterogeneous and conflicting. In contrast, the consistent drop in surgery/colectomy rates suggests that the growing use of immunosuppressants and biological agents has had a positive impact on the course of IBD. Most clinical trial data indicate that the risk of serious infections is not increased in patients treated with anti-tumour necrosis factor alpha [TNFα] agents, but a different picture emerges from cohort studies. The use of thiopurines increases the risk for non-melanoma skin cancers and to a lesser extent for lymphoma and cervical cancer [absolute risk: low], whereas no clear increase in the cancer risk has been reported for anti-TNF agents. Finally, the majority of studies reported in the literature do not reveal any increase in mortality with immunosuppressant therapy or biologicals/anti-TNF agents.

We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of GCG (encoding preproglucagon), PYY, CCK, GIP, GHRL (encoding ghrelin), SCT (encoding secretin), NTS (encoding neurotensin) and NR1H4 (encoding farnesoid X receptor) was evaluated.The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups, GHRL, SCT and GIP mRNA was reduced after RYGB while PYY, CCK, NTS and NR1H4 gene expression was unaltered. GCG mRNA was upregulated in both groups.Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG.

Background and Aims: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases [IBD] between Eastern and Western Europe. The aim of this study was to analyse the differences in the disease phenotype, medical therapy, surgery, and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis. Methods: Nine Western, five Eastern European centres and one Australian centre with 258 Crohn’s disease [CD], 380 ulcerative colitis [UC] and 71 IBD unclassified [IBDU] patients [female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years] participated. Patients’ data were registered and entered in the web-based ECCO-EpiCom database [www.epicom-ecco.eu]. Results: In CD, 36 [19%] Western Europe/Australian and 6 [9%] Eastern European patients received biological therapy [ p = 0.04], but the immunosuppressive [IS] use was equal and high in these regions [Eastern Europe vs Western Europe/Australia: 53% vs 45%; p = 0.27]. Surgery was performed in 17 [24%] CD patients in Eastern Europe and 13 [7%] in Western Europe/Australia [ p < 0.001, p LogRank = 0.001]. Of CD patients from Eastern Europe, 24 [34%] were hospitalized, and 39 [21%] from Western Europe/Australia, [ p = 0.02, p LogRank = 0.01]. In UC, exposure to biologicals and colectomy rates were low and hospitalization rates did not differ between these regions during the 1-year follow-up period [16% vs 16%; p = 0.93]. Conclusions: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared with Western Europe/Australia, whereas significantly more CD patients were treated with biologicals in the Western Europe/Australian centres.

Background The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Methods Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. Results For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. Conclusion The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.

Aim To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB. Methods Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas. Results GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice. Conclusion GN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.

Background and aims: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort.Methods: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria.Results: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed.Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

Cost analysis in a prospective European population-based inception cohort : is there a cost-saving effect of biological therapy?

Background The use of biologic therapy has increased significantly during the last decade. In 2015, one in three Crohn’s disease (CD) patients and one in five ulcerative colitis (UC) patients had received biologics within 2 years of diagnosis 1 in Denmark (DEN), Sweden (SWE) and Norway (NOR). Whether this change in treatment strategy has resulted in changes in the use of conventional drugs (5-aminosalicylates [5-ASA], immunomodulators [IM] or corticosteroids) remains unknown. An aim of this study was to investigate the use of these drugs in the biological era.1 Høivik ML et al. Time to first treatment with biologic agents for ulcerative colitis and Crohn’s disease across four Nordic countries: Results from the TRINordic study, Submitted to ECCO 2020. Methods A total of 67,758 incident IBD patients (42,894 UC, 24,864 CD) diagnosed between 2010 to 2017 were included in a nationwide cohort in DEN, NOR and SWE. Information on drug treatment was extracted from the National Patient Registries and the National Prescription Registries. Patients were required to have at least 1-year of follow-up post-diagnosis; results are limited to patients diagnosed between 2010 to 2016, inclusive. Results During 2010 to 2016, cumulative exposure to 5-ASA in CD patients at 2 years after diagnosis declined from 19.0%, 39.0% and 50.5% in 2011 to 16.3%, 31.1% and 39.6% in 2016 in DEN, NOR and SWE, respectively (p < 0.001). The opposite trend was observed in UC where 87.3–91.1% received 5-ASA within 2 years in 2015 compared with 75.8–87.3% in 2011 (p < 0.001) (Figure 1). In all countries, corticosteroid use remained stable in CD with more than half of patients receiving corticosteroids within 2 years of diagnosis. In UC, corticosteroid use within 2 years of diagnosis increased in NOR from 42.2% in 2011 to 51.6% in 2015 (p < 0.001) but remained stable in DEN and SWE (Figure 2). The use of IM within 2 years increased in CD patients in NOR and SWE from 36.5% and 40.8% in 2010 to 51.3% and 52.1% in 2015 (p < 0.001). IM were less frequently used in UC but increased similarly from 14.0% and 21.1% in 2010 to 22.5% and 26.4% in 2015 (p < 0.001). In DEN, IM use remained stable over time (Figure 3). Conclusion The use of 5-ASA declined over time in patients diagnosed with CD but increased over time in patients diagnosed with UC. Corticosteroid use remained stable in CD but increased over time in UC patients in NOR. The increasing and earlier use of biologics was accompanied by increasing use of IM in all countries. While this could suggest a more aggressive treatment approach, differences in treatment practices across countries might contribute to these findings. The impact of changes in treatment strategies on disease outcomes remains to be shown.

Results: A total of 95 patients (62% females; median age 45 yr) were included in the study and allocated 4.8 g mesalazine per day. Of these, 82 (86%) patients were adherent to web therapy, completing 3 months of web-guided mesalazine therapy. Of the 82 adherent patients, 72 (88%) continued mesalazine and 10 (12%) needed rescue therapy. From weeks 0 to 12, patients had experienced a significant reduction in mean SCCAI (4.6 versus 1.6, P , 0.001), mean FC (437 versus 195, P , 0.001), and mean TIBS (6.7 versus 2.4, P , 0.001). Based on TIBS values (#1), the dose of mesalazine was reduced to 2.4 g in 25% of patients at week 3 in 50% of subjects at week 5 and in 88% of patients at week 12. Conclusions: Web-guided therapy with mesalazine in mild-to-moderate ulcerative colitis helps to individualize the dose and improve adherence to therapy. The study confirms mesalazine efficacy in mild-to-moderate UC, significantly improving TIBS values in majority of the patients. (Inflamm Bowel Dis 2014;20:2276–2285)

Background and aims: The aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohn's and Colitis Organization–Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia. Methods: Fourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. Results: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohn's disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p = 0.02). Conclusion: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort. * Abbreviations: : IBD : inflammatory bowel diseases CD : Crohn's disease UC : ulcerative colitis IBDU : inflammatory bowel disease unclassified ECCO : European Crohn's and Colitis Organization EpiCom : Epidemiological Committee IRR : incidence rate ratio CI : confidence interval EC-IBD : European Collaborative Study on Inflammatory Bowel Disease ACCESS : Asia-Pacific Crohn's and Colitis Epidemiology Study SE : standard error

Background and Aims: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. Methods: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1. million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. Results: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p.

The 2015 EpiCom survey evaluated population, patient, and research registries across Europe. Information was collected from 38 countries. The registries included those falling within the remit of national statistics, hospital databases, twin and multiplex registries, inflammatory bowel disease [IBD] registries and biobanks, and cancer and surgical registries. The scale and nature of registries were investigated, and where possible a contact detail for each registry was obtained.The survey demonstrated 33 birth and death registers across Europe. It also highlighted ethical and legal challenges in linking information from health and social registries: 30 delegates reported that their home country has a hospital database; 21 have adverse events registers, although the majority only mandate reporting of events that occur during drug trials; 17 countries have twin registries; And IBD registries have been established in 19 countries, with 15 countries having a biobank with IBD samples. The cancer registries were the most complete and consistent.Despite heterogeneity between countries, the registries represent an invaluable source of information for future IBD research. Supplementary material [available at ECCO-JCC online] depicts active registries in each of the participating countries.

Background. The treatment of chronic inflammatory bowel disease (IBD) is costly, and limited resources call for analyses of the cost effectiveness of therapeutic interventions. The present study evaluated the equivalency of the Short Form 6D (SF-6D) and the Euro QoL (EQ-5D), two preference-based HRQoL instruments that are broadly used in cost-effectiveness analyses, in an unselected IBD patient population.Methods. IBD patients from seven European countries were invited to a follow-up visit ten years after their initial diagnosis. Clinical and demographic data were assessed, and the Short Form 36 (SF-36) was employed. Utility scores were obtained by calculating the SF-6D index values from the SF-36 data for comparison with the scores obtained with the EQ-5D questionnaire.Results. The SF-6D and EQ-5D provided good sensitivities for detecting disease activity-dependent utility differences. However, the single-measure intraclass correlation coefficient was 0.58, and the Bland-Altman plot indicated numerous values beyond the limits of agreement.Conclusions. There was poor agreement between the measures retrieved from the EQ-5D and the SF-6D utility instruments. Although both instruments may provide good sensitivity for the detection of disease activity-dependent utility differences, the instruments cannot be used interchangeably. Cost-utility analyses performed with only one utility instrument must be interpreted with caution.

Natural disease course of inflammatory bowel disease unclassified in a prospective European population-based inception cohort-the Epi-IBD cohort

Summary Background Infliximab (IFX) maintenance therapy for Crohn's disease (CD) is administered every 8 weeks, but inter-patient variation in optimal treatment intervals may exist. Aim To assess, in a prospective pilot study, the efficacy, safety and quality of life (QoL) of IFX maintenance treatment scheduled through web-based self-monitoring of disease activity. Methods Twenty-seven CD patients in IFX maintenance therapy were enrolled and received a standardised disease education and web-training. Using the http://www.cd.constant-care.dk concept, patients recorded their disease activity and faecal calprotectin weekly. From this, the inflammatory burden (IB) score was calculated, placing patients in the green, yellow or red zones of a ‘traffic light’ system. If placed in the yellow or red zones, the computer directed these patients to consult their physician for IFX infusion. Results Seventeen patients (63%) completed 52 weeks of follow-up, 6 (22%) completed 26 weeks and 4 (15%) were excluded due to loss of response, patient decision or non-adherence. In total, 121 IFX infusions were given with a median interval of 9 (range: 4–18) weeks. Only 10% of infusions were given at 8-week intervals, whereas 39% were administered with shorter and 50% with longer intervals respectively. The mean IB and the QoL remained stable during the web-treatment. One mild infusion reaction and one case of folliculitis were observed, while three patients underwent surgery. Conclusions The program http://www.cd.constant-care.dk appears to be a practical and safe concept for the individualised scheduling of maintenance treatment with IFX in patients with Crohn's disease. Larger studies are awaited to confirm this preliminary outcome.

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disorder. Systemic inflammation increases the risk of atherosclerosis and ischaemic heart disease (IHD). Objective To examine the impact of IBD, including its duration and treatment, on the risk of IHD. Methods In a nationwide population-based cohort of 4.6 million Danes aged ≥15 years, we compared people diagnosed with IBD during 1997–2009 (n=28 833) with IBD-free individuals. Subjects with IHD were identified in the National Patient Register. Using Poisson regression, we estimated the incidence rate ratios (IRRs) for IHD with 95% CI with adjustment for age, gender, socioeconomic status, calendar year and use of drugs for comorbidities. Results A markedly increased risk of IHD was seen within the first year after IBD diagnosis (IRR=2.13 95% CI 1.91 to 2.38). During 1–13 years of follow-up after IBD diagnosis, the risk of IHD was 1.22 (95% CI 1.14 to 1.30). The risk of IHD was lower among patients with IBD using 5-aminosalicylic acids (IRR=1.16; 95% CI 1.06 to 1.26) than among non-users (IRR=1.36; 95% CI 1.22 to 1.51) (p=0.02), in particular among oral corticosteroid users, used as a proxy for disease severity. Likewise patients treated surgically or with thiopurines and tumour necrosis factor α antagonists tended to have reduced IRRs for IHD. Conclusions The risk of IHD was highest in the first year after IBD diagnosis, possibly owing to ascertainment bias. The increased long-term risk of IHD in IBD may be related to chronic inflammation, and interventions reducing the inflammatory burden may attenuate this risk.

Background The EpiCom-study investigates a possible East-West-gradient in Europe in the incidence of IBD and the association with environmental factors. A secured web-based database is used to facilitate and centralize data registration. Aim To construct and validate a web-based inception cohort database available in both English and Russian language. Method The EpiCom database has been constructed in collaboration with all 34 participating centers. The database was translated into Russian using forward translation, patient questionnaires were translated by simplified forward-backward translation. Data insertion implies fulfillment of international diagnostic criteria, disease activity, medical therapy, quality of life, work productivity and activity impairment, outcome of pregnancy, surgery, cancer and death. Data is secured by the WinLog3 System, developed in cooperation with the Danish Data Protection Agency. Validation of the database has been performed in two consecutive rounds, each followed by corrections in accordance with comments. Results The EpiCom database fulfills the requirements of the participating countries' local data security agencies by being stored at a single location. The database was found overall to be "good" or "very good" by 81% of the participants after the second validation round and the general applicability of the database was evaluated as "good" or "very good" by 77%. In the inclusion period January 1st –December 31st 2010 1336 IBD patients have been included in the database. Conclusion A user-friendly, tailor-made and secure web-based inception cohort database has been successfully constructed, facilitating remote data input. The incidence of IBD in 23 European countries can be found at www.epicom-ecco.eu.

Background The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities9 focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients9 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. Methods 333 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 patients9 compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. Results 88% 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. Conclusion The 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.

Aliment Pharmacol Ther 2010; 32: 859–871 Summary Background The evidence concerning the use of isosorbide-mononitrate (IsMn) for oesophageal varices is equivocal. Aim To assess the effects of IsMn for patients with oesophageal varices and no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention). Methods Systematic review with meta-analyses of randomized trials on IsMn alone or with beta-blockers or endoscopic therapy for oesophageal varices. Electronic and manual searches were combined. Randomized trials on primary and secondary prevention were included. The primary outcome measure was mortality. Intention-to-treat random effects meta-analyses were performed. The robustness of the results was assessed in trial sequential analyses. Results Ten randomized trials on primary and 17 on secondary prevention were included. Evidence of bias was identified. No apparent effect of IsMn on mortality compared with placebo or beta-blockers or IsMn plus beta-blockers vs. beta-blockers was identified. Compared with endoscopic therapy, IsMn plus beta-blockers had no apparent effect on bleeding, but did seem to reduce mortality in secondary prevention (RR 0.73, 95% CI 0.59–0.89), but not in primary prevention. The effect of IsMn plus beta-blockers on mortality in secondary prevention was not confirmed in trial sequential analysis. Conclusions Isosorbide-mononitrate used alone or in combination with beta blockers does not seem to offer any reduction in bleeding in the primary or secondary prevention of oesophageal varices. Compared with endoscopic therapy, there may be a survival advantage in using IsMn and beta-blockers, but additional large multicentre trials are needed to verify this finding.

Aliment Pharmacol Ther 31, 735–744 Summary Background Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn’s disease (CD) patients is complex, but necessary. Aims To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Methods Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Results Over 10 years, 630 UC and 318 CD patients had 22,823 and 11 871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. Conclusions Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.