Crohn’s disease significantly impairs health-related quality of life (HRQoL), even during remission. The double-blinded, randomised controlled STOP IT trial1 investigated outcomes following infliximab (IFX) withdrawal in patients in sustained clinical-biochemical-endoscopic remission, showing 48% relapse rate within 48 weeks of withdrawal, but did not assess HRQoL. This study evaluated longitudinal HRQoL trajectories to determine whether a decline in HRQoL is detectable prior to clinical relapse following discontinuation of biologics. Post hoc analysis of STOP IT.1 Patients were followed for 48 weeks after randomisation with predefined study visits. HRQoL was assessed at each visit using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) comprising 10 questions each scored from 1 (severe problem) to 7 (not a problem at all). Relapse was defined as CDAI ≥150 together with CDAI increase ≥70 above baseline over 2 consecutive weeks. For patients who experienced clinical relapse between scheduled visits, an early termination visit was conducted, and this SIBDQ measurement was defined as event time. Longitudinal changes in SIBDQ were analysed using linear mixed-effects models. A segmented regression restricted to patients who relapsed was used to estimate the inflection point at which HRQoL began to decline prior to relapse. One hundred patients with Crohn’s disease were included. Forty-six patients discontinued treatment (intervention group), and 22 (48%) had relapse within 48 weeks. In the control group where all 54 patients continued IFX therapy, none experienced a relapse. Baseline SIBDQ was comparable between patients who later experienced relapse and those who did not (median 61, IQR 56–65 vs. 61, 54–66; p = 0.98). At time of clinical relapse, SIBDQ was significantly lower among patients who relapsed (median 43, IQR 36-55 vs. 61, 54-65; p < 0.001). In mixed-effects analyses, SIBDQ remained stable in patients who did not relapse (β = -0.01 [-0.05 – 0.02]; p = 0.51), whereas patients who relapsed showed a significantly decline over time (β = -0.46 [-0.63 – -0.30]; p < 0.001). In segmented regression restricted to relapsing patients, an inflection point was identified 7 weeks prior to clinical relapse. SIBDQ remained stable until this time (β = 0.04, [-0.18 – 0.26]; p = 0.72) and thereafter sharply declined (β = -2.26 [-2.90 − -1.61]; p < 0.001). Significant HRQoL impairment presented 7 weeks prior to manifestation of clinical relapse in Crohn’s disease patients discontinuing IFX while in clinical-biologic-endoscopic remission, supporting SIBDQ as a practical, non-invasive tool for early detection of potential loss of disease control. References: 1Buhl S et al. NEJM Evidence 2022;1:EVIDoa2200061. Conflict of interest: Nissen, Mathilde Jepsen: No conflict of interest Gill, Prabhpreet: No conflict of interest Buhl, Sine: No conflict of interest Brynskov, Jørn: No conflict of interest Christensen, Katrine Risager: No conflict of interest Dorn-Rasmussen, Maria: No conflict of interest Thomsen, Ole Ostergaard: No conflict of interest Klausen, Tobias Wirenfeldt: No conflict of interest Dahlerup, Jens Frederik: No conflict of interest Sorensen, Heidi Gram: No conflict of interest Jahnsen, Jørgen: No conflict of interest Molazahi, Akbar: No conflict of interest Pedersen, Natalia: No conflict of interest Kjeldsen, Jens: No conflict of interest Almer, Sven: No conflict of interest Dahl, Eva: No conflict of interest Vind, Ida: No conflict of interest Cannon, Annett: No conflict of interest Marshall, Jan: No conflict of interest Sipponen, Tiana: No conflict of interest Agnholt, Jørgen Steen: No conflict of interest Kievit, Linda Hendrika Adriana: No conflict of interest Aure, Synnøve Louise: No conflict of interest Martinsen, Lars: No conflict of interest Meisner, Svetlana: No conflict of interest Møller Hansen, Jane: No conflict of interest Ainsworth, Mark Andrew: No conflict of interest Steenholdt, Casper: Lectures for Takeda, MSD and Janssen-Cilag research grant from Takeda.

ABSTRACT Background Low‐dose thiopurine therapy in combination with allopurinol (LD‐THIO/ALLO) is a widely used treatment for inflammatory bowel disease (IBD). However, little is known about the effects of in utero exposure to this combination on pregnancy and birth outcomes. Methods In this retrospective, single‐center study, we included all patients with IBD treated with LD‐THIO/ALLO during conception and pregnancy between 2013 and 2023 at the Gastro Unit, Hvidovre Hospital, Copenhagen. Data were collected from electronic medical records and questionnaires. Results In total, 44 women with 62 pregnancies, including one twin pregnancy, and 59 live births were included. There was one spontaneous abortion and three induced abortions due to fetal genetic disorders, one because of trisomy 21 and two because of spinocerebellar ataxia. Obstetric complications occurred in eight pregnancies (13%), including preeclampsia, HELLP syndrome, hypertension, and/or gestational diabetes mellitus. Seven women (11%) had an IBD flare during pregnancy, none of which resulted in obstetric complications. Five children (9%) were born preterm, and four (7%) had low birth weight. No congenital malformations were reported. One child was born with facial nerve paralysis and was later diagnosed with hyper‐IgD syndrome. In total, 84% of the children were breastfed during maternal LD‐THIO/ALLO treatment. During the first year of life, one child had repeated infections and was transiently suspected of having an immune defect. Conclusions In this large, single‐center experience of LD‐THIO/ALLO treatment during pregnancy, no malformations or indications of increased risk of complications in pregnancy or birth were observed. Most children were breastfed, and no serious safety signals were reported in the first year of life. Treatment with LD‐THIO/ALLO appears to be safe during both pregnancy and breastfeeding.

INTRODUCTION:Endoscopic classification of ulcerative colitis (UC) shows high interobserver variation. Previous research demonstrated that artificial intelligence (AI) can match the accuracy of central reading in scoring still images. We now extend this assessment to longer colon segments and integrate AI into clinical workflows, evaluating its use for real-time, video-based classification of disease severity, and as a support system for physicians. METHODS:We trained a convolutional neural network with the Mayo Endoscopic Subscores (MESs) of 2,561 images and 53 videos from 645 patients. The model differentiated scorable from unscorable endoscopy sections through open-set recognition. Validation involved 140 video clips from 44 patients with UC. Six inflammatory bowel disease (IBD) experts and 16 nonexperts rated these videos, with expert scores as the gold standard. We assessed the model's performance and the value as a supporting system. Last, the model underwent an alpha test on a real-world patient as a real-time endoscopic support. RESULTS:The model achieved an accuracy of 82%, with no significant differences between the experts and the AI. When used as a supporting system, it improved non-IBD experts' performance by 12% and disagreed with the primary physician in 20%-39% of cases. During the alpha test, it was successfully integrated into clinical practice, accurately distinguishing between MES 0 and MES 1, consistent with endoscopists' assessments. DISCUSSION:Our innovative AI model shows significant potential for enhancing the accuracy of UC severity classification and improving the proficiency of non-IBD experts. It is designed for clinical use and has proven feasible in real-world testing.

BACKGROUND:5-Aminosalicylate (5-ASA) is recommended for the treatment of mild-to-moderate ulcerative colitis (UC). However, adherence may be low; poor adherence is associated with an increased risk for flares. AIM:To investigate whether a regimen of a single 1600 mg tablet of 5-ASA improves adherence with preserved remission rates compared to a conventional regimen of three 800 mg tablets. METHODS:We enrolled 178 patients with UC (89 per group) in this open-label randomised controlled phase IV trial. Patients had to have stable remission on 5-ASA for at least 2 months and no concomitant diseases that could affect compliance. We randomised patients (1:1) to either receive Asacol 1600 mg single tablet or Asacol 2400 mg (three tablets of 800 mg once daily) for 12 months. Patients were assessed five times during the 12 months, where medicine was delivered and received, blood and stool samples were collected and symptom scores were determined. RESULTS:Eighty-two patients taking a single tablet and 78 taking three tablets were adherent (p = 0.32). Fewer patients in the 1600 mg group missed doses (24.5 vs. 26.5). There was no difference in the number of relapses or proportions experiencing relapse. Neither adherence nor treatment group was a significant predictor of relapse. CONCLUSION:The single-tablet lower dose treatment could be a feasible alternative to the conventional three-tablet regimen. TRIAL REGISTRATION:The study was registered at Clinicaltrials.gov (ID NCT04133194) and approved by The Danish Medicine Agency and The National Committee on Health Research Ethics (EudraCT 2019-002070-31).

INTRODUCTION:Inflammatory bowel disease [IBD] patients have a relapsing-remitting disease course, and amongst environmental factors that aggravate the disease course, common drugs aside from non-steroidal anti-inflammatory drugs have not been studied in detail. While the microbiome is considered to play a significant role on the disease course, the impact of antibiotics is poorly understood. This study investigated the potential impact of different classes of antibiotics on the course of disease in IBD using the Danish National Patient Registry. METHODS:Danish IBD patients were studied using two nested case-control cohorts exploring associations between antibiotic types and IBD flare-ups, defined as IBD-related hospitalizations and/or high-dose systemic steroid exposure. Multivariate logistic regression and eXtreme Gradient Boosted decision tree [GBDT] machine learning methods evaluated antibiotic risks. RESULTS:Two cohorts with 15 636 and 5178 patients were analysed for risk of hospitalization and course of steroids, respectively. The risk of a flare-up was significantly increased with antecedent exposure to quinolones (ATC:J01M; odds ratio [OR]: 3.04-3.82), antimycotics [ATC:J02A; OR: 1.50-2.30], agents against amoebiasis and protozoal infections [ATC:P01A; OR: 1.95-3.18], intestinal anti-infectives [ATC:A07A; OR: 2.09-2.32], and beta-lactam antibiotics [ATC:J01C; OR: 1.36]. The GBDT models achieved an area under the curve of 0.71-0.85 for predicting flare-ups, with the same above-mentioned antibiotics being in the ten most important variables. CONCLUSION:We found distinctive antibiotics to be significantly associated with an increased risk of IBD flare-ups. Our findings are corroborated by our GBDT machine learning models. Healthcare providers should be aware of the deleterious potential of specific antibiotic groups in patients with IBD only using these agents in a restrictive manner or preferentially consider alternative antibiotic groups.

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease decreasing life quality through symptoms such as bloody diarrhoea and abdominal pain. Endoscopy is a cornerstone of diagnosis and monitoring of UC. The Mayo endoscopic subscore (MES) index is the standard for measuring UC severity during endoscopic evaluation. However, the MES is subject to high inter-observer variability leading to misdiagnosis and suboptimal treatment. We propose using a machine-learning based MES classification system to support the endoscopic process and to mitigate the observer-variability. The system runs real-time in the clinic and augments doctors’ decision-making during the endoscopy. This project report outlines the process of designing, creating and evaluating our system. We describe our initial evaluation, which is a combination of a standard non-clinical model test and a first clinical test of the system on a real patient.

Introduction: 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. Methods: 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. Results: 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. Discussion: 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.

BackgroundWhether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse.ResultsThis study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported.ConclusionsDiscontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

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<0·001 compared to the experts). Interpretation: We propose a new, standardised way of evaluating endoscopic images from UC patients for both clinical and academic purposes. We demonstrate how our DL model is highly capable of distinguishing between all four MES levels of activity. This model will optimize and standardize the evaluation of disease severity measured by the MES across all centres and hospitals, no matter their level of medical expertise. Funding: None received. Declaration of Interest: B. Lo, Z. Liu, C. Igel has nothing to declare I. Vind has received either consulting or lecture fees from Tillotts Pharma AB, AbbVie A/S, Janssen-Cilag A/S, Takeda Pharma A/S. F Bendtsen have received consulting fees, lecture fess or research funds from Takeda Pharma A/S, Norgine Danmark A/S, Ferring Pharmaceuticals A/S J Burisch has received consulting fees from Celgene, Janssen-Cilag, AbbVie, Vifor Pharma, Jansen and Ferring; lecture fees from Abbvie, Pfizer, MSD, Pharmacosmos and Takeda Pharma, and unrestricted grant support from Takeda Pharma and Tillotts Pharma. Ethical Approval: This study was approved by the local hospital board as a quality insurance/improvement study.

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: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.

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

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. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.

Introduction 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. Methods 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. Results 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. Conclusions 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: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 < 0.001] patients received ≥ 500 mg corticosteroid within a year, resulting in 781 patient-years at risk of osteoporosis. Of those, only 83 [10.6%] patient-years were followed by a dual-energy X-ray absorptiometry scan within the same or the following 2 years.Overall, 73 [14.2%] IBD patients (CD: 31 [14.6%], UC: 42 [14%]) and 680 [6.6%, p < 0.001] controls were diagnosed with osteoporosis during follow-up. The risk of osteoporosis was increased compared to the control population (odds ratio: CD: 2.9 [95% confidence interval: 2.0-4.1], UC: 2.8 [2.1-3.9]). 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.

Paediatric onset IBD (pIBD) has been reported to be more aggressive than adult onset IBD (aIBD). Yet, a more extensive disease presentation in paediatric onset ulcerative colitis (pUC) has been the only consistent finding. In a population-based study, we aimed to further elucidate the differences in disease course between pIBD and aIBD. We compared a pIBD cohort (diagnosis <15 years of age) and an aIBD cohort (diagnosis ≥18 years of age). Medical records were retrieved manually at last follow-up, and clinical data concerning IBD phenotype and treatment were registered. We included 333 pIBD and 449 aIBD patients. Patients with pIBD more often presented with extensive disease localisation than aIBD (24%/9% of pCD/aCD with L4 disease localisation and 67%/24% of pUC/aUC with E3 disease extent). Of the patients with inflammatory disease at diagnosis, 34% and 16% of pCD and aCD patients, respectively, progressed to complicated disease over the first 7 years after diagnosis ( P  = .002). Patients with pUC were more often treated with systemic corticosteroids (HR: 2.0 [CI: 1.6-2.6], P  < .0001) and/or thiopurines (HR: 3.8 [CI: 2.8-5.2], P  < .0001). Lastly, pIBD patients more often received biologics (HR: 2.5 [CI: 1.8-3.6, P  < .0001] in CD and HR: 3.8 [CI: 2.1-6.9, P  < .0001] in UC) and had an increased risk of relapse (incidence rate ratio of 1.8 [CI: 1.4-2.2, P  < .0001]). In this population-based cohort study we demonstrated a more severe disease course in pIBD than in aIBD. This message should be considered by both paediatric and adult gastroenterologists when caring for pIBD patients.

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 (sic)1.6 and (sic)0.3 million for CD and UC, respectively. The total costs amounted to (sic)42.6 million. Only patients with extensive colitis had significantly higher direct costs (proctitis: (sic)2273 [1341-4092], left-sided: (sic)3606 [2354-5311], extensive: (sic)4093 [2313-6057], p <0.001). No variables were significantly associated with increased total costs in CD or in UC patients. 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.

BACKGROUND: The existing population-based comparative studies between adult onset IBD (aIBD) and pediatric onset IBD (pIBD) consistently report, that pediatric onset of ulcerative colitis (pUC) present with more extensive disease. In this population-based study, we aim to further characterize the differences in the natural history between pIBD and aIBD. METHODS: AIBD patients included (>18 years of age) were diagnosed from January 2003 to December 2004. PIBD patients were diagnosed from January 1998 to December 2008 (<15 years of age). Both cohorts are population-based. All medical records were retrieved manually at time of last follow-up, and clinical data concerning IBD phenotype (Montreal classification 1 ) and treatment were registered. Number of relapses were recorded as defined by Romberg-Camps et al 2 . Differences regarding medical treatment and surgery was calculated using Cox regression analysis. Comparison of risk of relapse (IRR) was calculated using Poisson regression. All other comparisons were calculated using Chi 2 . RESULTS: 446 aIBD (CD/UC 183/263) and 333 pIBD (CD/UC/IBDU 166/145/22) patients were included. Median follow-up time was 7.6 years (aIBD) and 8.9 years (pIBD). In CD, 9% aCD and 24% pCD ( P < 0.0001) patients had involvement of the upper GI tract (L4a or L4b either alone or in combination with L1-L3). At diagnosis, 22% and 12% of aCD and pCD, respectively, had non-inflammatory behavior and at end of follow-up this increased to 37% and 48%, respectively ( P = 0.04). 24% and 66% of aUC and pUC, respectively, had extensive disease (E3) at diagnosis ( P < 0.0001). A total of 14% and 42% of aIBD and pIBD patients, respectively, were treated with anti-TNF-alpha (HR: 3.2 (2.4–4.4), P < 0.0001) during follow-up. The increased risk was independent of IBD diagnosis and disease extent. In UC, 41% and 74% of aUC and pUC, respectively received either azathioprine or 6-mercatopurine (IM) during follow-up (HR 3.8 (2.8–5.2), P < 0.0001). This increased risk in pUC was independent of disease extent. Over the first 7 years after diagnosis pIBD patients had an increased risk of relapse compared to aIBD patients IRR 1.8 (CI 1.4–2.2), P < 0.0001. The increased risk of relapses persisted when adjusting for IBD diagnosis and extension. At end of follow-up bowel resection occurred in 18% and 29% of aIBD and pIBD, respectively, resulting in a hazard ratio of 1.4 (CI 0.97–2.0) and 0.9 (CI 0.5–1.7), P = 0.07 in CD and UC, respectively. CONCLUSION(S): PIBD patients had more extensive disease than aIBD patients, were more often treated with immunomodulators and biologic agents and had an increased risk of relapse. Moreover, pCD patients more often developed non-inflammatory behavior and a trend towards increased risk of surgery was noted. Compared to previous results this population-based cohort study demonstrated a clearly more severe disease course in pIBD than in aIBD. Consequently, pIBD patients must be monitored intensively and the top-down treatment protocol should be investigated for pIBD. As a future consequence of the severe disease course and frequent use of immunosuppressive medicine, attention should be paid towards the possible increased cancer risk in these patients.

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 and aims: Despite promising results, only a few studies have been published on serum calprotectin as a biomarker in IBD. Recently, plasma measurements of calprotectin have been shown to be more reliable than serum measurements. In this study, we aim to assess plasma and serum calprotectin measurements as biomarkers of disease activity in paediatric and adult ulcerative colitis.Methods: Paediatric (5-18 years) and adult (>18 years) patients scheduled for colonoscopy due to suspected or confirmed ulcerative colitis were included prospectively. Stool and blood samples were collected at time of colonoscopy and patient symptom scores were recorded. At colonoscopy the Ulcerative Colitis Endoscopic Index of Severity was recorded. Histology was graded according to the Geboes score.Results: 84 patients where included; 30 paediatric and 54 adult patients. Plasma calprotectin had a stronger correlation to all outcome variables than serum calprotectin. Plasma calprotectin correlated positively to disease extent (Rho = 0.53, p < .0001), symptoms scores (Rho = 0.54, p = .002, only in the paediatric cohort), endoscopic scores (Rho = 0.39, p = .0003), histological scores (Rho 0.28, p = .01) and, when using endoscopic assessment of severity as reference, could discriminate active disease from patients in remission (p = .03).Conclusions: While more studies are needed to assess if plasma calprotectin can discriminate healthy individuals from ulcerative colitis, this study indicates that plasma calprotectin can be used as a biomarker of disease activity, especially in cases where faecal calprotectin measurements are cumbersome either due to patient compliance or logistical requirements.