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Background Patients with inflammatory bowel disease [IBD] including Crohn’s disease [CD] and ulcerative colitis [UC] are at risk of developing metabolic bone disease. The aims here were to investigate the screening strategy, incidence and risk factors of osteoporosis in a prospective population-based inception cohort. Method Between 2003 and 2004 all incident patients diagnosed with CD and UC in a well-defined Copenhagen area were included and followed until 2015. Data were compared with a control population [at a ratio of 1:20]. Regression models were performed with several covariates. The sensitivity of the Danish registries for osteoporosis was also assessed. Results A total of 513 patients were included [213 CD, 300 UC]. Overall, 338 (66%, CD: 164 [77%], UC: 174 [58%], p Overall, 73 [14.2%] IBD patients (CD: 31 [14.6%], UC: 42 [14%]) and 680 [6.6%, p Conclusion In this population-based inception cohort, the incidence of osteoporosis was significantly higher compared to a control population. Measurement of bone mineral density is infrequent, especially in patients at high risk of developing osteoporosis. These results demonstrate the need of further awareness of the risk of osteoporosis among IBD patients, and prospective population-based studies are warranted.

The evaluation of endoscopic disease severity is a crucial component in managing patients with ulcerative colitis (UC). However, endoscopic assessment suffers from substantial intraobserver and interobserver variations, limiting the reliability of individual assessments. Therefore, we aimed to develop a deep learning model capable of distinguishing active from healed mucosa and differentiating between different endoscopic disease severity degrees.One thousand four hundred eighty-four unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independently of one another according to the Mayo endoscopic subscore (MES). In cases of disagreement, a third expert classified the images. Different convolutional neural networks were considered for automatically classifying UC severity. Five-fold cross-validation was used to develop and select the final model. Afterward, unseen test data sets were used for model evaluation.In the most challenging task-distinguishing between all categories of MES-our final model achieved a test accuracy of 0.84. When evaluating this model on the binary tasks of distinguishing MES 0 vs 1-3 and 0-1 vs 2-3, it achieved accuracies of 0.94 and 0.93 and areas under the receiver operating characteristic curves of 0.997 and 0.998, respectively.We have developed a highly accurate, new, automated way of evaluating endoscopic images from patients with UC. We have demonstrated how our deep learning model is capable of distinguishing between all 4 MES levels of activity. This new automated approach may optimize and standardize the evaluation of disease severity measured by the MES across centers no matter the level of medical expertise.

Background Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center. Methods We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed. Results The population consisted of 327 Crohn’s disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2–5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559–0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736–1.349). Conclusions The annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

BACKGROUND: Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab.AIMS: To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life METHODS: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance.RESULTS: In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring.CONCLUSIONS: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

Objectives Real-world data about sustained clinical remission (SCR) and treatment optimization with vedolizumab for ulcerative colitis (UC) and Crohn's disease (CD) are scarce. We aimed to investigate the short and long-term effectiveness and safety of vedolizumab in a real-world cohort in Denmark. Methods A retrospective two-center cohort study was conducted between November 2014 and November 2019 with the primary outcomes of clinical remission (CR) at weeks 14, 30, 52 and 104 and SCR defined as CR at week 14 through week 52. Results The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. Rates of CR at weeks 14, 30, 52 and 104 were 36.6, 35.1, 34.0 and 27.8%, respectively, in UC, and 31.7, 30.1, 26.5 and 22.4% in CD. SCR was achieved in 19.6 and 20.0%, respectively. In UC and CD, optional dosing of vedolizumab at week 10 (odds ratio [OR] = 0.23 (95% confidence interval [CI], 0.03-1.17), and OR = 0.68 (95% CI, 0.22-2.04)), as well as increase of frequency (OR = .26 (95% CI, 0.01-2.86), and OR = 0.19 (95% CI, 0.01-1.45)), were not associated with CR at week 52. Furthermore, combination treatment with azathioprine was not associated with long-term outcomes. However, dose intensification of vedolizumab successfully restored CR in 65.2 and 57.1% of patients with UC and CD experiencing loss of response. Conclusions Vedolizumab is effective in achieving and restoring short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10, and simultaneous treatment with azathioprine, did not improve long-term outcomes.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are associated with reduced health-related quality of life (HRQoL), but findings differ between studies. The aim of this study was to analyse the impact of disease activity and social factors on HRQoL. METHOD: A total of 513 patients diagnosed with UC and CD between 2003 and 2004, in a population-based setting, were followed for 7 years. HRQoL was assessed using the Short Form-12, the Short Inflammatory Bowel Disease (IBD) Questionnaire (SIBDQ), the Work Productivity and Activity Impairment Questionnaire: General Health and a national health survey. Associations were assessed using multiple linear regressions. RESULTS: A total of 185 of the eligible patients (UC: 107 (50.2%) and CD: 78 (50.3%)) were included. No differences in disease-specific or generic HRQoL were found between CD and UC patients, and IBD patients did not differ compared with the background population. The majority of CD (73.1%) and UC (85.0%) patients had ‘good’ disease-specific HRQoL using the SIBDQ. Unemployment for ≥ 3 months occurred more in CD vs UC patients(30.6 vs 15.5%, p = 0.03); however, sick leave for ≥ 3 months did not differ significantly (17.4 vs 11.4%, p = 0.4). Using multiple linear regressions, unemployment, sick leave and disease activity were the factors most frequently associated with reduced HRQoL. CONCLUSION: In a population-based cohort with 7 years of follow-up, HRQoL did not differ between patients and the background population.

Background Inflammatory bowel disease [IBD], encompassing Crohn’s disease [CD] and ulcerative colitis [UC], places a high burden on health care resources. To date, no study has assessed the combined direct and indirect cost of IBD in a population-based setting. Our aim was to assess this in a population-based inception cohort with 10 years of follow-up. Methods All incident patients diagnosed with CD or UC, 2003–2004, in a well-defined area of Copenhagen, were followed prospectively until 2015. Direct and indirect costs were retrieved from Danish national registries. Data were compared with a control population [1:20]. Associations between the costs and multiple variables were assessed. Results A total of 513 (CD: 213 [42%], UC: 300 [58%]) IBD patients were included. No significant differences were found in indirect costs between CD, UC, and the control population. Costs for CD patients were significantly higher than those for UC regarding all direct expenditures (except for5-aminosalicylates [5-ASA] and diagnostic expenses). Biologics accounted for €1.6 and €0.3 million for CD and UC, respectively. The total costs amounted to €42.6 million. Only patients with extensive colitis had significantly higher direct costs (proctitis: €2273 [1341–4092], left-sided: €3606 [2354–5311], extensive: €4093 [2313–6057], p Conclusions In this prospective population-based cohort, direct costs for IBD remain high. However, indirect costs did not surpass the control population. Total costs were mainly driven by hospitalisation, but indirect costs accounted for a higher percentage overall, although these did decrease over time. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Background: Evaluation of endoscopic disease severity is a key component in the management of patients with ulcerative colitis (UC). However, endoscopic assessment suffers from substantial intra- and inter-observer variation of up to 75%, thereby limiting the reliability of individual assessments. Our aim was to develop a deep learning (DL) model capable of distinguishing active from healed mucosa, as well as to differentiate between different degrees of endoscopic disease activity. Methods: 1,484 unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independently of one another according to the Mayo endoscopic subscore (MES). In cases of disagreement, a third expert classified the images. Convolutional neural networks, including InceptionNetV3 and EfficientNetB0-B4, were considered in the development of our DL model. Five-fold cross-validation was used to develop and select the best model. Unseen test datasets were used to evaluate the models. The accuracy, sensitivity, specificity, positive and negative predictive values, and Cohen’s kappa were used to evaluate the final models. Findings: In the most difficult task – distinguishing between all four categories of MES – our final model achieved a mean accuracy of 0·82, a mean AUC of 0·99, test accuracy of 0·84, sensitivity of 0·88, specificity of 0·81 and a weighted Cohen’s kappa of 0·83 (p

The Danish National Patient Registry (DNPR) has been the source of several epidemiological studies of inflammatory bowel disease (IBD). However, the validation dates back to 1996 and lacks outpatient records and disease classification. The aim of this study was to update the validation and assess the validity and reliability of using the registry in disease classification.Validation of the registry was done using a population-based inception cohort of IBD patients from 2003 to 2011 consisting of 513 patients. Specificity and sensitivity were calculated for the diagnoses of Crohn's disease (CD) and ulcerative colitis (UC), age at diagnosis and disease classification according to the Montreal Classification at both time of diagnosis and end of follow-up.The registry showed high validity and reliability in identifying CD and UC patients concerning correct age classification and identifying perianal disease. The registry showed inconsistent, unreliable results in further disease classification.The DNPR has good validity and reliability in identifying patients with CD and UC, and defining the age of patients at diagnosis. However, categorising IBD patients according to the Montreal Classification should not be carried out using DNPR data in their current form, except when identifying CD patients with perianal disease.

Background & Aims Patients with Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk of developing intestinal cancer. However, less is known about the risk of extraintestinal cancers (EICs). The aim of this study was to conduct a systematic review and meta-analysis of population-based cohorts assessing the risk of EICs in inflammatory bowel disease (IBD) patients. Methods Only population-based studies reporting on the prevalence or incidence of EICs were included. In total, 884 studies were screened and those included were assessed for quality. Eligible studies were pooled for length of follow-up evaluation, events in the IBD population, and events or expected events in a control population for the meta-analyses. Results In total, 40 studies were included in the systematic review and 15 studies were included in the meta-analysis. The overall risk of EICs was found to be increased in both CD (incidence rate ratio [IRR]: 1.43 [CI, 1.26, 1.63]) and UC (IRR: 1.15 [1.02, 1.31]) patients. Both CD and UC patients presented with an increased risk of skin (IRR: CD, 2.22 [1.41–3.48]; UC, 1.38 [1.12–1.71]) and hepatobiliary (IRR: CD, 2.31 [1.25–4.28]; UC, 2.05 [1.52–2.76]) malignancies. Furthermore, CD patients showed an increased risk of hematologic (IRR, 2.40 [1.81–3.18]) and lung (IRR, 1.53 [1.23–1.91]) cancers. These increased risks were present despite treatment with immunosuppressives. Conclusions This systematic review and meta-analysis shows that both CD and UC patients are at an increased risk of developing EICs, both overall and at specific sites. However, additional studies with longer follow-up evaluation are needed to assess the true risk of EICs posed by IBD.

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.

BACKGROUND: The inflammatory bowel disease disability index (IBD-DI) was developed recently. The aim was to translate the IBD-DI into Danish and validate it for future clinical studies and practice, and to assess the level of disability among IBD patients.PATIENTS AND METHODS: The IBD-DI was translated using a transcultural adaptation method. Between January and December 2017, patients from three outpatient clinics in three different regions in Denmark were given the final version of the IBD-DI for self-completion. Validation was carried out according to guidelines. Disability level was assessed among the entire cohort and in various subgroups.RESULTS: A total of 200 patients were included in the study, including 112 Crohn's disease (CD) and 88 ulcerative colitis (UC) patients. The response rate was 90%. The IBD-DI showed excellent reliability and validity. CD patients showed worse disability levels than UC patients [mean (SD): CD: 37.3 (20.2) vs. UC: 21.7 (16.4); P=0.04]. In both CD and UC, significantly increased disability levels were found between patients with active disease, use of steroid and extraintestinal manifestation (PCONCLUSION: A valid and reliable version of the IBD-DI is now available in Danish for future studies. Several clinical factors are shown to affect the levels of disability among patients with CD and UC. The disability levels are significantly increased in patients with active disease, treated with systemic steroids, and extraintestinal manifestations are present in both CD and UC. Further testing of the Danish IBD-DI is needed to assess its responsiveness and interpretability.

Background Real-world data about treatment optimization of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD) are scarce. Therefore, we aimed to investigate the influence of administration of a supplementary dose of vedolizumab at week ten on short and long-term outcomes. Methods A retrospective two-center cohort study was conducted between November 2014 and November 2019. The primary outcomes were clinical remission (CR) at weeks 14, 30, 52, and 104 and Sustained CR (SCR) defined as CR at week 14 through week 52. Results The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. As shown in Table 1, patients with CD receiving or not receiving the additional dosing at week ten were comparable in terms of disease activity at weeks 0 and 6, while patients with UC receiving the dosing at week 10 experienced higher disease activity at week 0 but not week 6. The overall efficacy of vedolizumab in UC and CD stratified according to treatment with the optional dosing at week ten is summarized in Figures 1 and 2, demonstrating no statistically significant difference among patients receiving or not receiving vedolizumab at week 10. Furthermore, the optional dosing of vedolizumab at week 10 (odds ratio (OR)=0.23 (95%CI 0.03-1.17), and OR=0.68 (95%CI 0.22-2.04)), was not associated with CR at week 52 among patients with UC and CD, respectively. Conclusion Vedolizumab is effective in achieving short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10 did not improve long-term outcomes.

Background and Aim Crohn's disease [CD] is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery. Few population-based studies have investigated the predictors for disease progression and surgery in CD according to the Montreal classification. We aimed to identify clinical predictors associated with complicated CD in a Danish population-based inception cohort during the biologic era. Methods All incident patients with CD in a well-defined Copenhagen area, between 2003 and 2004, were followed prospectively until 2011. Disease progression was defined as the development of bowel stricture [B2] or penetrating disease [B3] in patients initially diagnosed with non-stricturing/non-penetrating disease [B1]. Associations between disease progression and/or resection, and multiple covariates, were investigated by Cox regression analyses. Results In total, 213 CD patients were followed. A total of 177 [83%] patients had B1 at diagnosis. Patients who changed location had increased risk of disease progression (hazard ratio [HR] = 3.1, 95% CI: 1.12,8.52). Biologic treatment was associated with lower risk of change in location [HR = 0.3, 95% CI: 0.1-0.7]. Colonic involvement [L2 or L3 vs L1] was associated with a lower risk of surgery (HR = 0.34/0.22, 95% CI: [0.13,0.86]/[0.08,0.60]). All CD patients who progressed in behaviour or changed location had an increased risk of surgery [p < 0.05]. Conclusions This population-based inception cohort study demonstrates that changes in disease location or behaviour in patients with CD increase their risk of resection. Our findings highlight the protective effect of biologic treatment with regard to change in disease location, which might ultimately improve the disease course for CD patients.

Background and aims Disease extent in ulcerative colitis [UC] is dynamic and can progress over time. Little is known about risk factors for UC extension in the era of biologics. We investigated the risk of UC extension and subsequent risk of surgery in a Danish population-based cohort. Methods All incident UC cases in a strictly defined Copenhagen area between 2003 and 2004 were followed prospectively through 2011. Disease extension was defined as patients with limited UC [E1 or E2] at diagnosis having progressed from the initial extent by colonoscopy or surgery to E2 or extensive colitis [E3]. Associations between progression or colectomy and multiple covariates were analysed by Cox regression analysis. Results Of 300 UC patients, 220 [73%] had E1 or E2 at diagnosis. During follow-up, 50 [23%] patients with E1/E2 progressed to E3, and 22 [10%] with E1 progressed to E2. Disease extent at diagnosis was the sole predictor of extension to E3. A total of 18 [8%] patients with E1/E2 at diagnosis had a colectomy. Progression from E1/E2 to E3, female gender and a history of smoking were risk factors for colectomy. Conclusion After 7 years of follow-up, 33% of patients with limited UC experienced disease extension. Only extent at diagnosis was a clinical predictor for disease extension. The risk of colectomy was increased in former smokers and patients who progressed to extensive colitis. This highlights the need to prevent disease progression in patients with limited UC, and to identify new histological or molecular markers that might help stratify risks for disease progression.

Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed a significant increase (p = 0.03) in CD patients. We found a change in the microbial abundance in UC patients with active disease and in CD patients with aggressive disease. These results suggest that dysbiosis of the gut in IBD patients is not only related to current activity but also to the course of the disease.

Background Evaluation of endoscopic disease severity is a key component in the management of ulcerative colitis (UC) patients. However, endoscopic assessment suffers from substantial intra- and interobserver variation, up to 75 %, thereby limiting the reliability of individual assessments. Our aim was to develop an artificial intelligence (AI) model capable of distinguishing active from healed mucosa as well as to differentiate different levels of endoscopic disease activity. Methods 1484 unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independent of each other according to the Mayo endoscopic subscore (MES). In case of disagreement, a third expert classified the images. Different convolutional neural network architectures were implied in the development of the AI model. Five-fold cross-validation was employed to select the best model. Unseen test data were used for evaluation. The final model was evaluated on its performance for distinguishing MES 0 from 1–3, MES 0–1 (i.e. mucosal healing) from 2–3, and distinguish between all MES. The accuracy, sensitivity, specificity, positive and negative predictive value, and Cohen’s Kappa were used to evaluate the final models. Results Our final model achieved at the most difficult task (distinguishing between all 4 categories of MES) a mean accuracy of 0.82, mean AUC of 0.99, test accuracy of 0.84, a sensitivity of 0.88, and a specificity of 0.81 and a weighted Cohens Kappa of 0.83 (p The results from the other tasks are shown in table 1. Conclusion We propose a new standardised way of evaluating endoscopic images from UC patients for both clinical and academic purposes. The proposed AI model demonstrated a very good capability of distinguishing between all 4 MES levels of activity. This will optimize and unify the evaluation of the disease severity measured by the Mayo endoscopic subscore across all centres and hospitals no matter the level of medical expertise.

Background It remains unknown whether infliximab (IFX) successfully can be discontinued once Crohn's disease (CD) patients have attained sustained, complete clinical, biochemical, and endoscopic remission. No randomized, placebo (PBO) controlled trial has previously assessed this. Methods This double-blind, randomized, PBO-controlled multicenter trial enrolled patients with luminal CD who had been treated with standard IFX maintenance therapy for at least 1 year, in complete remission at the time of inclusion defined as CD Activity Index (CDAI) 150 with an increase in CDAI >70-point from baseline over two consecutive weeks; or definitive clinical relapse requiring immediate intervention as judged by treating physician) in the intention-to-treat population. Results The study population comprised 115 patients (n=54 female; age median 34 years [IQR 26-50]; disease duration median 6 years [3-12]; IFX treatment duration median 23 months [16-39]). All patients were in combined clinical- (CDAI median 41 [IQR 15-66]), biochemical- (CRP median 3mg/L [IQR 2-4]), and endoscopic- (Simple Endoscopic Score for CD median 0, [IQR 0-0] (n=99)) remission. Patients were randomized to continued IFX therapy (n=59) or to start PBO infusions (n=56) (Figure 1). Time to relapse was significantly shorter among patients who discontinued IFX as compared to those continuing IFX (p 150) the figures were 47% in the PBO group vs. 98% in IFX group (p Conclusion This first double-blinded placebo-controlled RCT of IFX withdrawal in Crohn's disease patients strongly suggests that discontinuation of IFX leads to a considerable risk of relapse despite combined clinical, biochemical, and endoscopic remission. Download : Download high-res image (53KB) Download : Download full-size image Download : Download high-res image (56KB) Download : Download full-size image

AIM: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research.STUDY POPULATION: The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated.MAIN VARIABLES: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology.DESCRIPTIVE DATA: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200-1,300 new biological therapies are initiated each year in Danish patients with IBD.CONCLUSION: The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).

Background Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5-aminosalicylic acid among unselected patients with ulcerative colitis. Methods The authors conducted a 7-year follow-up study of a population-based inception cohort of 243 Danish patients with ulcerative colitis diagnosed from 2003 to 2004. Compliance was defined as consumption of ≥80% of prescribed oral 5-aminosalicylic acid. Data were collected from medical records and the Danish National Prescription Database. They performed Cox regression analysis with adjustments for demographic and clinical characteristics to examine risk of recurrence (defined by increased use of oral 5-Aminosalicylic Acid, other additional treatment, or colectomy) in compliant versus noncompliant patients. Results In total, 182 patients (75%) experienced at least 1 recurrence during follow-up. For the first year after diagnosis, risk of recurrence did not differ significantly between compliant and noncompliant patients. For 1 to 3 years (hazard ratio: 0.46, 95% CI, 0.33-0.63) and 3 to 8 years (hazard ratio: 0.42, 95% CI, 0.32-0.55) after diagnosis, risk of recurrence was significantly decreased among noncompliant patients compared with that of compliant patients. Conclusions This unselected cohort study revealed a reverse association between compliance and recurrence of ulcerative colitis. This is unlikely to be explained by severe confounding because the authors were able to adjust for several demographic and clinical factors. Results may instead reflect that patients during recurrence-free periods through self-management choose not to take their medication.

Background Perianal complications in patients with Crohn's disease are common and have a negative impact on the patients' quality of life. Data about the long-term disease course of perianal Crohn's disease in the era of biological treatment are limited. In this population-based cohort study, we sought to investigate the occurrence, clinical risk factors, and disease course of perianal disease. Methods A total of 213 Crohn's disease patients were included in a prospective population-based inception cohort. Data were retrieved from medical records and national health administrative databases. Perianal disease was defined as a perianal fistula and/or abscess. Associations between outcomes and covariates were analyzed by Cox regression analysis. Results A total of 48 (22.5%) patients developed perianal disease after 10 years. Colonic disease location (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.01-3.92) and penetrating behavior (HR, 5.65; 95% CI, 2.65-12.03) were associated with the development of perianal disease. The cumulative risk of undergoing abdominal surgery was 51% after 10 years. Patients with perianal disease had a higher rate of resection (HR, 3.92; 95% CI, 1.86-8.67) and hospitalization (HR, 1.01; 95% CI, 1.00-1.01). There was no significant difference in the rate of sick leave, unemployment, or disability pension between patients with and without perianal disease. Conclusions Patients with perianal disease carry a higher risk of surgery and hospitalization, and this suggests a more severe disease course and poorer prognosis among these patients, even in the era of biological treatment. These findings underline the importance of optimizing treatment strategies for patients with perianal disease.

SummaryBackground The Inflammatory Bowel Disease Disability Index (IBD-DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC). Aim To assess the severity of disability and associated factors using the IBD-DI, and review the validity of the IBD-DI as a tool. Method Systematic review of cross-sectional studies. Patients included had UC or CD and were classified as active, in remission, or needing surgery, biological and/or steroid treatment. We included studies assessing disability using the IBD-DI and that were captured by electronic and manual searches (January 2017). The possibility of bias was evaluated with the Newcastle-Ottawa Scale. Results Nine studies were included with 3167 patients. Comparatively, patients with active disease had higher disability rates than those in remission (SMD [CI95] = 1.49[1.11, 1.88], I2 = 94%, P

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.

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.

In this population-based 7-year follow-up of incident patients with ulcerative colitis (UC) or Crohn's disease (CD), we aimed to describe disease progression and surgery rates in an era influenced by the increased use of immunosuppressants and the introduction of biological therapy.From 1 January 2003 to 31 December 2004, all incident cases (562) of patients diagnosed with UC, CD, or inflammatory bowel disease unclassified in a well-defined Copenhagen area were registered. Medical records were reviewed from 1 November 2011 to 30 November 2012, and clinical data were registered. Clinical data on surgery, cancer, and death were cross-checked with register data from national health administrative databases in order to include missed data.In total, 513 patients (213 CD and 300 UC) entered the follow-up study. Twenty-six patients changed diagnosis during the follow-up. Changes in disease localization and behavior in CD according to the Vienna classification were observed in 23.9% and 15.0% of the patients, respectively, during follow-up. In total, 28.3% of the 300 UC patients had disease progression during the follow-up. The overall use of systemic steroids, immunomodulators, and anti-tumor necrosis factor agents in CD was 86.4%, 64.3%, and 23.5%, respectively. The rate of first-time intestinal resection in CD was 29.1% (n=62), and the 7-year cumulative risk was 28.5%. The cumulative risk of colectomy in UC was 12.5% at 7 years.UC and CD are dynamic diseases that progress in extent and behavior over time. The resection rate in CD and the colectomy rate in UC are still relatively high, although the rates seem to have decreased compared with historic data, which could be due to an increase in the use of immunomodulating therapy.

Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1 are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer.

Aliment Pharmacol Ther 2011; 34: 1217–1224 Summary Background Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). Aim To compare phenotype, treatment and disease course in children (

Background: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. Methods: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). Results: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). Conclusions: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.

A global gene expression profile of non-inflamed colonic mucosal cells from patients with Crohn's disease (CD) and of colonic mucosal cells from controls was performed.Tissue specimens from macroscopically non-inflamed descending colon were obtained colonoscopically from 33 CD patients and from 17 control subjects. All controls and 10 CD patients were medication-free at the time of colonoscopy. The Human Genome U133 Plus 2.0 GeneChip Array was used for gene profiling. Hybridization data were analysed with dChip software. Results were confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Protein product expression of selected genes was assessed by immunohistochemistry using the Envision+ visualization technique.The expression profile was not homogeneous with the statistical cut-point settings applied. In comparison with controls, it was found that 19 CD patients had three differentially expressed genes, two of them related to the innate immune system: dual oxidase 2 on chromosome 15 (DUOX2, fold change 4.1) and lipocalin 2 on chromosome 9 (LCN2, fold change 3.1). The third gene, regenerating islet-derived 1 alpha (REG1A, fold change 3.9), codes for a mitogenic protein; this could not be confirmed by RT-PCR. Medication-free patients had no differentially expressed genes as compared with controls. Immunohistochemistry indicated that these proteins were produced by epithelial cells (REG1A, LCN2) and leucocytes (DUOX2 and LCN2).As compared with controls, non-inflamed colonic mucosal cells contain two up-regulated genes related to the innate immune system. Up-regulation of these genes, known to be induced by microorganisms, suggests either increased microflora antigenicity or an altered function in mucosal barrier defence.

BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe.METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register.RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51).CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

BACKGROUND: To assess the occurrence and risk of unemployment (UE), sick leave (SL), and work disability (WD) in incident patients with inflammatory bowel disease (IBD) after 7 years of follow-up compared with the background population and to determine outcome predictors.METHODS: The study population consisted of patients aged 18 to 67 years (N = 379) from an IBD inception cohort registered January 1, 2003, and to December 31, 2004, in the Copenhagen area. Clinical data were retrospectively collected from medical records. Data on UE, SL, and WD were retrieved from national registries. A random subset of the general population (n = 1435) were matched with IBD cases based on sex, age, and residency. The cumulative probabilities of UE, SL, and WD were calculated. A Cox proportional hazard regression was performed to identify possible outcome predictors.RESULTS: There was no difference in UE rates between patients with IBD and controls (P = 0.23). The risk of SL was significantly increased in patients with IBD (hazard ratio 2.0; 95% confidence interval 1.7-2.4). Patients with IBD showed a higher risk of WD (hazard ratio 2.1; 95% confidence interval 1.2-3.8), particularly male patients older than 55 years. The rate of WD in CD (5.8%) was markedly lowered compared with previous studies. Within the IBD population, sex, educational level, disease behavior, smoking status, and surgery were predictors of UE, SL, and WD.CONCLUSIONS: The observed increased risk of SL and WD in patients with IBD underscores the need for the early identification of risk factors. A multidisciplinary approach to secure IBD patients' participation in the labor market is recommended.

Quality-of-life tests are used because they provide information about symptoms, potential complications, and response to treatment with patients as active participants. We took Crohn's disease (CD) during diet supplement with omega 3 or 6 fatty acids (ω-3FA vs. ω-6FA) Impact® as an example and assessed three quality-of-life tests: The inflammatory bowel disease questionnaire (IBDQ), the Beck depression inventory (BDI), and the visual analogue scale (VAS). These tests have been found inconvenient, not informative in daily clinical use, and inhomogeneous in international studies. We used the body mass index (BMI) (kg/m2) as a clinical quantitative effect parameter and the patient self-rated quality of life as qualitative variables during recovery. All ratings were converted into numeric standardized percent point before isolation of optimized ratings. BMI increased on average 2 BMI units in both diet groups. The classical wellness tests or their traditional sub-scores identified improved outcome during recovery, primarily in the ω-3FA group. Separate items on bowel function, wellness, and asthenia possessed the best item responsiveness - (30-35 percent point). A new selective scale with the six most responsive items is proposed as a specific optimized questionnaire. Based on CD as an example, we described a method to isolate responsive items from quality-of-life tests and described a method to optimize their sensitivity. We propose for validation a new optimized disease - specific VAS scale for rating of wellness during treatment in inflammatory bowel disease, in which ω-3FA seemed superior in improving outcome.

A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City.All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered.Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported.The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients. METHODS: In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohn's disease (CD) patients form the basis for the present study. RESULTS: In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004). CONCLUSIONS: Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Objective: The aim of this study is to evaluate the cumulative probability of recurrence and admission rates in an inflammatory bowel disease (IBD) inception cohort diagnosed in 2003–2004. Methods: Data on medications, phenotypes and surgery for 513 individuals with ulcerative colitis (UC, n = 300) and Crohn's disease (CD, n = 213) were obtained from medical records and linked to population-based health administrative database information. The admission rates and cumulative probability of recurrences were estimated, and the association with the baseline factors and medication was tested. Results: The cumulative risk of first recurrence after 1, 5 and 7 years was 40%, 63%, and 66% in CD patients and 51%, 75%, and 79% in UC patients, respectively. The cumulative risk of first surgical relapse was 6%, 18%, and 23% at 1, 5 and 7 years in CD respectively. One hundred and CD patients (66%) and 142 UC patients (47%) had at least one IBD-related hospitalisation. The hospitalisation rate decreased from 7.0 days/person-year in year one to 0.9 day at year 5 in CD, and from 4.7 days to 0.4 days for UC patients. Age above 40, current smoking, stricturing behaviour, and disease localisation (colonic, ileocolonic, and upper-GI) at diagnosis were predictors of recurrence in CD. In UC, age above 40 and former smoker status were predictors of recurrence and left-sided and extensive colitis were predictors of first-time hospitalisation. Conclusion: In an era of improved treatment options, the recurrence rates, but not the surgery or hospitalisation rates, have decreased for CD but not for UC. The phenotypic characteristics at diagnosis predict the risk of recurrence and hospitalisation. * Abbreviations : 6-MP : 6-Mercaptopurine Anti-TNF : Anti-tumour necrosis factor alpha AZA : Azathioprine CD : Crohn's disease CE : Capsule endoscopy CPR : Central person registration CT : Computed tomography ECCO : European Crohn's and Colitis Organisation EC-IBD : European Collaborative Study Group on Inflammatory Bowel Disease NPR : The National Patient Registry MRI : Magnetic resonance imaging IBD : Inflammatory bowel disease IBDU : Inflammatory bowel disease unclassified IMM : Immunomodulators RCT : Randomised clinical trial SMI : Small bowel imaging UC : Ulcerative colitis US : Ultra sonography

Summary Background : Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. Aim : To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. Methods : The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. Results : Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon-γ, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1β and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1β, interleukin-6, interferon-γ, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. Conclusions : The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder.

Background: A North-South gradient in Crohn’s disease (CD) implying a higher incidence in northern Europe compared to southern Europe has been established. Aims: To investigate whether there is a difference between Denmark and Portugal in the frequency of CARD15 mutations in CD patients compared to a healthy background population and to compare genotype-phenotype relations in the two countries. Methods: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. Results: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates in Danish patients were significantly different (p = 0.02) compared with Danish controls, no difference (p = 0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p = 0.03) using the Mantel-Haenszel test. No difference in evolution of phenotypes and the CARD15 status in CD was found during follow-up between the two matched populations. Ileal disease correlated to high occurrence of CARD15. Conclusion: No North-South gradient regarding occurrence of CARD15 was revealed. Although a trend towards more mutations in the Portuguese controls was seen, a relationship between CD and CARD15 mutations was observed in both countries.

Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). This may be caused by the disease activity itself and/or the medical treatment, and both may lead to changes in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The aim of the present study was to examine the effects of enteral nutrition, Impact Powder, as adjuvant therapy to corticosteroid treatment on changes in the GH/IGF-I axis in patients with Crohn's disease (CD).The patients were randomized to 3-IP (omega-3-fatty acid (FA), 3 g/day) or 6-IP (omega-6-FA, 9 g/day). Changes in total IGF-I (tIGF-I) and total IGF-II (tIGF-II), free IGF-I (fIGF-I), IGF binding proteins (IGFBP-1 and IGFBP-3), IGFBP-3 protease activity and insulin levels were examined in 31 patients with active CD (CDAI: 186-603) during treatment with prednisolone (40 mg for 1 week) and tapering the dose by 5 mg/week. Clinical and biochemical markers of inflammation were studied at day 0, and after 5 and 9 weeks.There were no differences at baseline between the two groups. During the treatment period, tIGF-I, fIGF-I and IGFBP-3 increased significantly in both groups compared to baseline (p0.05) without differences between the groups. Insulin and IGFBP-1 showed no significant changes throughout the treatment period.There was no difference between 3-IP and 6-IP as adjuvant enteral nutrition on the GH/IGF-I axis. The changes observed in the GH/IGF-I axis are in line with previously published studies and may be explained by corticosteroid treatment; however, we cannot exclude an additional effect of omega3-/omega6 FA as adjuvant enteral nutrition.

Background/Aims: Familial Crohn’s disease has shown concordance concerning location and clinical type of the disease especially among monozygotic twins. Susceptibility to Crohn’s disease is both based on genetic and environmental factors. We investigated polymorphisms of CARD15, TLR4, and OCTN, and environmental factors in a monozygotic twin pair with Crohn’s disease and their first-degree relatives. Methods: 22-year-old monozygotic female twins with ileocolonic Crohn’s disease and their healthy brother and parents were examined. DNA samples from patients and relatives were genotyped for CARD15, TLR4,and OCTN polymorphisms. ASCA and p-ANCA analyses were performed. Additionally, patients and relatives filled out a questionnaire concerning multiple environmental factors. Results: Both twins presented in the same year with identical Vienna Classification phenotypes: stenotic behavior (B2) and localization in terminal ileum and colon (L3). Both carried a CARD15 R702W variant, but had normal alleles in TLR4 and OCTN. They were smokers since the age of 15, used oral contraceptives and had undergone appendectomy. The healthy father and brother were CARD15 R702W positive, were non-smokers and had not undergone appendectomy. Conclusion: This case report is the first to describe complete concordance in CARD15 status, phenotypic appearance, and smoking, appendectomy and oral contraceptive use in a pair of monozygotic twins with CD.

Les maladies inflammatoires intestinales sont associees a une augmentation du risque de developper un cancer colorectal (CCR). La duree et l’etendue de la maladie sont des facteurs de risque importants, de meme que la presence d’une cholangite sclerosante primitive (CSP) et un diagnostic a une âge precoce. La chimioprevention du cancer vise a empecher, arreter ou renverser la phase d’initiation ou de progression des cellules neoplasiques vers le cancer. Un interet croissant a ete accorde aux agents chimiopreventifs potentiels dans la CCR sporadique et associee a la colite. Plusieurs etudes ont montre qu’une prise reguliere de 5-aminosalicylates peut apporter une certaine protection contre le developpement de la CCR dans les MICI. Chez les patients porteurs de colite ulcereuse ou de CSP, il a ete demontre que l’acide ursodeoxycolique pouvait reduire le risque de CCR. L’acide folique ne semble pas protecteur contre le cancer. Cet article donne un resume d’un grand nombre d’etudes de diverses provenances, epidemiologiques,in vivo etin vitro, qui ont etudie la question de la chemoprevention dans les MICI. Inflammatory bowel disease (IBD) is associated with an increased risk of developing colorectal cancer (CRC). Both duration and extent of disease are important risk factors, as is the presence of primary sclerosing cholangitis (PSC) and early age at diagnosis. Chemoprevention of cancer aims to prevent, arrest or reverse the initiation phase or the progression of neoplastic cells to cancer. A growing interest in possible chemopreventive agents, in both sporadic and colitisassociated CRC has occurred. Several studies have indicated that regular intake of 5-aminosalicylates can provide some protection against the development of CRC in IBD. In patients with ulcerative colitis and PSC ursodeoxycolic acid has been shown to reduce the risk of CRC. Folic acid has not been proven cancer protective in IBD. The current review gives an overview of the evidence of a variety of sources including epidemiological, in vivo, and in vitro studies that have addressed the question of chemoprevention in IBD.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe.METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up.RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population.CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.