Search

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers., Competing Interests: Declaration of interests JB reports personal fees from AbbVie, Celgene, Pfizer, Samsung Bioepis, Pharmacosmos, Ferring, and Galapagos; grants and personal fees from Janssen, MSD, Takeda, Tillots Pharma, and Bristol Myers Squibb; and grants from Novo Nordisk. MZ has received support for attending a meeting from Takeda. PDC has received grants or contracts from Janssen, Takeda, Ferring, Shire, AbbVie, Celltrion, and Baxter. PDC has been a speaker, consultant, and advisory board member for AbbVie, Janssen, Takeda, Celltrion, Ferring, Shire, and Baxter; received support for travel or attending meetings or both from Ferring, Shire, Janssen, AbbVie, Takeda, Celltrion, and Baxter; and has been a member of the Australia and New Zealand IBD Research Consortium. SV has received research grants from Pfizer, Galapagos, AbbVie, Johnson & Johnson, and Takeda; consulting fees from AbbVie, AbolerIS Pharma, Agomab, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma, Zealand Pharma; speaker fees from Alimentiv, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, Pfizer, Takeda, and Tillots Pharma. CNB has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharma, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; is a consultant for Mylan Pharmaceuticals and Takeda; and educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. CNB is on the speaker's panel for AbbVie Canada, Janssen Canada, Medtronic Canada, and Takeda Canada; and has received research funding from AbbVie Canada and Pfizer Canada. GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Amgen, Sandoz, Pendopharm, and Takeda. He has received research support from Ferring. He shares ownership of a patent: treatment of inflammatory disorders, autoimmune disease, and pbc (WO2019046959A1. PCT/CA2018/051098) since Sept 7, 2018. DD has received lecture or consultancy fees from Takeda, Janssen, and Pfizer, and support for travel or attending meetings or both from Janssen and Takeda. MW has received grants or contracts from Mitsubishi Tanabe Pharma, Takeda, Zeria Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical, Kyorin Pharmaceutical, AbbVie, EA Pharma, Kissei Pharmaceutical, and Alfresa Pharma; consulting fees from AbbVie, EA Pharma, Eli Lilly Japan, Gilead Sciences, Nippon Boehringer Ingelheim, and Takeda Pharmaceutical; and honoraria from EA Pharma, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Zeria Pharmaceutical, Pfizer Japan, Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceutical, Celltrion Healthcare, JIMRO, Eli Lilly Japan, and Mochida Pharmaceutical. LT has received grants or contracts from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, and Amgen; consulting fees from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, Fresnius Kabi, and Viatris; and honoraria for lectures from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, and Organon. KP is an employee of Genentech–Roche and a shareholder of the Roche Group. KHK has served as speaker, consultant, and advisory member for or has received research funding from AbbVie, Amgen, Enorasis, Epsilon Health, Dr Falk Pharma, Faran Ferring, Genesis, Grifols, Janssen, Koper, MSD, Mylan, Shire, Takeda, and Vianex. MLH has received investigator-initiated research grants from Tillotts, Ferring, Takeda, and Pfizer; advisory board honoraria from Takeda and AbbVie; and speaking fees from Takeda, AbbVie, Tillotts, Ferring, Galapagos, Janssen, and MSD. ZK has served as speaker for AbbVie, Takeda, Janssen, Freseinus, and Oktal Pharma/Celltrion. MC has served as a speaker, as a consultant, or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Biogen, Gilead, and Eli Lilly. EVL has received grants or contracts from AbbVie, Bristol Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, and UCB; consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, Janssen, Iterative Scopes, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Takeda, and UCB; reports the following patents: USA 11 249 084 (issued), USA 10 041 948 (issued), and USA 17 668 915 (pending); has participated on a data safety monitoring board or advisory board for Eli Lilly and Morphic; owns stock in Exact Sciences; and is a board member of Crohn's & Colitis Foundation, Minnesota-Dakotas Chapter. PLL has been a speaker or advisory board member, or both, for AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genentech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Takeda, Tillots, and Viatris, and has received unrestricted research grants from AbbVie, Gilead, Takeda, and Pfizer. JPG has served as a speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers Squibb, Gilead/Galapagos, Eli Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma. WB has received research grants from Vifor Pharma and B Braun Medical; consulting fees from Takeda and B Braun Medical; speaker fees from Medtronic, Takeda, B Braun Medical, and Johnson & Johnson; and is a stock owner of Semiflex Company. RBG has received grants or contracts from AbbVie and Janssen; consulting fees from AbbVie; and honoraria for lectures from AbbVie and Cornerstone Health. MDK has received grants or contracts from Pfizer, Takeda, Janssen, AbbVie, Eli Lilly, Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, and Arenapharm; consulting fees from Takeda and Pfizer; speaker fees from AbbVie; has participated on data safety monitoring board or advisory board for Eli Lilly; and owns stock in Johnson & Johnson. MJP has received grants or contracts from Takeda, Janssen, Galapagos, Tramedico, MSD, Takeda, Janssen, and Bristol Myers Squibb; honoraria for lectures from Bristol Myers Squibb, Janssen, AbbVie, and Galapagos; consulting fees from Janssen and Gilead; and has a leadership or fiduciary role in the MyCoach foundation. JMA has served as speaker, consultant, and advisory member for AbbVie, Allergan, Anatara, Atmo Capsule, Bayer, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Ferring Fresenius Kabi, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Pfizer, Sandoz, Shire, Takeda, and Vifor; has participated on a data safety monitoring board or advisory board for Janssen; has received research grants from the Royal Adelaide Hospital research fund, The Hospital Research Fund 2020–22, and The Helmsley Trust 2020–23. SCN has received grants or contracts from AbbVie, Ferring, and Olympus and Janssen; consulting fees from AbbVie, Pfizer, Ferring, and Janssen; honoraria for lectures from AbbVie, Ferring, Janssen, Menarini, Takeda, Tillotts and Pfizer; has participated on a data safety monitoring board or advisory board for AbbVie, Pfizer, Ferring, and Janssen; is a shareholder of GeniBiome; and is a director of the Microbiota I-Center, Hong Kong. HOM has received research grants from Takeda and Biogen, consulting fees from Takeda, and speaking fees from Pfizer and Biogen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Patients with longstanding inflammatory bowel disease [IBD] may be at an increased risk of death compared to the general population, especially elderly patients. The Inflammatory Bowel South-Eastern Norway [IBSEN] study has previously detected a small but not statistically significant increase in mortality 20 years after diagnosis. The aim of this study was to evaluate the overall and cause-specific mortality at 30 years of follow-up., Methods: The IBSEN cohort included 519 incident patients with ulcerative colitis [UC] and 237 patients with Crohn's disease [CD] between 1990 and 1993, each matched with five controls. Death certificate data were obtained from the Norwegian Cause of Death Registry. The underlying causes of death were categorized into five groups: all cancers, gastrointestinal cancers, cardiovascular diseases, infections and all other causes. Hazard ratios [HRs] were modelled using Cox regression., Results: There was no statistically significant difference in the overall mortality rates. However, in patients with CD, male sex (HR = 1.65 [95% CI: 1.04-2.62]), onset after 40 years of age (HR = 1.72 [1.19-2.48]), colonic disease (HR = 1.57 [1.05-2.35]) and penetrating behaviour (HR = 3.3 [1.41-7.76]) were clinical factors associated with an increased mortality. IBD patients were at a higher risk of death due to cardiovascular disease: HR = 1.51 [1.10-2.08] for UC and 2.04 [1.11-3.77] for CD. When taking into account both the underlying and the immediate cause of death, infection was more frequent in patients with IBD., Conclusions: Overall, all-cause mortality rates were similar between patients with IBD and controls. However, clinicians should remain alert to cardiovascular diseases and infections, particularly in specific subgroups of CD patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Objectives: The use of biologic therapy in inflammatory bowel disease (IBD) is likely to increase with lower costs and more biologics and biosimilars becoming available. Our aim was to estimate the trends in use of first-line biologics during the first year after diagnosis in a Norwegian IBD population from 2010 to 2016., Methods: Data were collected from the Norwegian National Patient Registry and Norwegian Prescription Database. Patients defined as incident IBD cases between 2010 and 2016 were included and followed for 12 months. Patients were stratified by year of diagnosis to examine change over time. Chi-square test was used for calculations on proportions. Time from diagnosis to first biologic was calculated by Kaplan-Meier failure estimates., Results: 14,645 patients were included, 5283 (36%) with Crohn's disease (CD) and 9362 (64%) with ulcerative colitis (UC). In the 2010 and 2016 cohort, the proportion initiating biologics increased from 17% to 33% ( p  < .001) for CD and 7% to 13% ( p  < .001) for UC. The most frequently used first-line biologics were infliximab (CD: 64% and UC: 82%) and adalimumab (CD: 36% and UC: 15%). The highest registered use of adalimumab was in the 2012 cohort (CD: 56% and UC: 39%). In the 2014-2016 cohorts, infliximab was the most used first-line biologic for both CD and UC., Conclusions: The proportion of IBD patients initiating biologics within 12 months after diagnosis increased between 2010 and 2016. The use of infliximab as first-line biologic increased after the approval of biosimilar infliximab in 2013.

Background and Aims: Patients with inflammatory bowel diseases (IBD) have experienced changes to the routine management because of the SARS-CoV-2 pandemic. The aim of this study was to examine patients with IBD's adherence to the restrictions imposed by society and the hospital, worries and concerns regarding medical treatment and clinical follow-up under the pandemic., Methods: IBD patients (≥18 years) at the outpatient clinic at Oslo University Hospital were included and answered a self-report questionnaire including concerns regarding their disease, medical therapy and follow-up during SARS-CoV-2 pandemic., Results: In total, 522 IBD patients were included, 317 Crohn's disease, 205 ulcerative colitis, 386 patients <50 years. Eighteen percent were in obligatory quarantine, and more often patients <50 years compared to patients ≥50 years. Five patients tested positive to SARS- CoV-2. A higher proportion <50 years reported worries for their medical treatment and risk of COVID -19 disease compared to those ≥50 years. Forty percent avoided family, two-thirds avoided friends, and 4% cancelled their scheduled consultation at the hospital. The hospital changed physical consultation to telephone consultation for 15% of the patients. The preferred follow-up was physical consultation. A higher proportion of the patients <50 years preferred telephone consultation compared to those ≥50 years. Four out of five IBD patients were satisfied with the information about their IBD and COVID-19., Conclusions: SARS-CoV-2 pandemic affects the daily lives for patients with IBD. It is important to develop evidence-base guidelines in follow-up and treatment, as well as patient information about COVID-19and IBD.

Our aim in this study was to analyze the importance of childbearing for risk of inflammatory bowel disease. Using data from the Norwegian Population Register and the Norwegian Patient Register, we fitted discrete-time hazard models for diagnosis of Crohn disease (CD) or ulcerative colitis (UC) among men and women aged 18-81 years in 2011-2016. Year and various sociodemographic factors were controlled for. The data included 4,304 CD cases and 8,866 UC cases. Women whose youngest child was ≤4 years of age had lower CD risk the following year than childless women (odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.62, 0.86). There was no such reduction in CD risk among fathers. Men whose youngest child was aged ≥20 years had higher risks of CD (OR = 1.22, 95% CI: 1.01, 1.49) and UC (OR = 1.15, 95% CI: 1.02, 1.30) than childless men. UC risk was also increased among men whose youngest child was aged ≤4 years (OR = 1.14, 95% CI: 1.02, 1.27). The short-term reduction in women's CD risk after a birth may reflect biological effects of pregnancy. Alternatively, it may reflect residual confounding or lifestyle effects of parenthood that are of special relevance for CD in women. In particular, differences in use of oral contraceptives (which it was not possible to control for) may have contributed to the observed pattern., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Serological antibodies have been associated with complicated disease course in Crohn's disease (CD), including the need for surgery. Aim: The aim of this study was to investigate if a panel of relevant antibodies could predict surgery in a prospective population-based cohort of patients with CD. Methods: The population-based IBSEN cohort has been followed prospectively for 20 years. At the 10- and 20-year follow-up, the following panel of serological antibodies was analysed: pANCA, ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1. At the 20-year follow-up or until lost to follow-up, all CD-related surgeries were registered. Results: Serum was available from 159 patients at 10-year follow-up and 135 patients at 20-year follow-up. In 113 patients, serum was available at both time points. No significant change of antibody status (positive vs. negative) was found from 10-year to 20-year follow-up. Negative pANCA, positive ASCA IgA and positive ASCA IgG at 10-year follow-up were all individually associated with increased risk for CD-related surgery. There was no association between anti-OmpC, anti-I2 or anti-CBir1 and CD-related surgery. In a multiple regression model including disease location and behaviour, only stricturing or penetrating disease behaviour and negative pANCA remained significantly associated with higher odds for surgery. Conclusion: Positive ASCA IgA and IgG, and negative pANCA were associated with higher odds for CD-related surgery in univariate analysis. Since disease phenotype changes during the disease course, while serological antibodies are stable, our results support the use of pANCA, ASCA IgA and ASCA IgG as prognostic markers in CD.

Background & Aims: Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis., Methods: We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis., Results: Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women., Conclusions: In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD)., Methods: IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance., Results: In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients., Conclusion: In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Background and Aims: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data., Methods: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010-2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis., Results: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn's disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway's health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD., Conclusions: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway's health regions during the three first years after IBD diagnosis.

Background and Aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC., Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute., Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities., Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD., Competing Interests: Competing interests: Phase 1 was funded thanks to an unrestricted educational grant to IOIBD from AbbVie and Tillotts. CAS has served as a consultant on advisory boards for AbbVie, Amgen, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Takeda, Theradiag and UCB; as a speaker for American Regent, AbbVie, Janssen, Pfizer and Takeda; and receives grant support from AbbVie, Janssen and Takeda. BMRS has research grants from Shire and Takeda. BF has served as a consultant for Abbott/AbbVie, Actogenix, Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared, Warner-Chilcott, Wyeth, Zealand and Zyngenia; has been a speaker for Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott and UCB Pharma; has served on advisory boards for Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics, Bristol-Myers Squibb, Celgene, Centocor, Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG and UCB Pharma; receives research funding from Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts and UCB Pharma; and serves on the board of directors for Robarts Clinical Trials. BS has served as a consultant for AbbVie, Celgene, Janssen Biotech, MedImmune, Takeda, Pfizer, TiGenix, Bristol-Myers Squibb, Receptos, Akros Pharma, Arena Pharmaceuticals, Theravance Biopharma R&D, Boehringer-Ingelheim, Synergy Pharmaceuticals, Toplvert Pharma, UCB and Lilly; has served on scientific advisory boards for Celgene, Janssen Biotech, MedImmune, Takeda, Pfizer, TiGenix and Lily; and he receives research funding from Celgene, Janssen Biotech, MedImmune, Takeda and Pfizer. EVL has consulted for UCB Pharma, Takeda, Janssen, AbbVie, Genentech, Celgene, Amgen, Mesoblast, Theradiag, Sun Pharma and Seres Health; has received research support from UCB Pharma, Takeda, Janssen, AbbVie, Genentech, Celgene, Amgen, Pfizer, Receptos, Gilead and Robarts Clinical Trials. RP has served as a consultant for Abbvie/Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Janssen, Merck, Schering-Plough, Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Warmer Chilcot, Takeda, Cubist and Celgene; on speaker's bureaus for Abbvie/Abbott, AstraZeneca, Janssen, Schering-Plough, Shire, Centocor, Elan, Prometheus, Warner Chilcott and Takeda; on advisory boards for Abbvie/Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Genentech, Janssen, Merck, Schering-Plough, Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Warner Chilcott, Takeda, Cubist, Celgene and Salix; and receives research/educational support from Abbvie, Abbott, Ferring, Janssen, Schering-Plough, Centocor, Millenium, Elan, Proctor and Gamble and Bristol-Myers Squibb. GD has served as advisor for Abbvie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Meyers Squibb, Boerhinger Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Ferring, DrFALK Pharma, Engene, Galapagos, Gilead, Glaxo Smith Kline, Hospira, Johnson & Johnson, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Novonordisk, Pfizer, Prometheus laboratories/Nestle, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; and received speaker fees from Abbvie, Ferring, Johnson & Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Shire, Millenium/Takeda, Tillotts and Vifor. CNB is supported in part by the Bingham Chair in Gastroenterology. He has served on advisory boards to Abbvie Canada, Janssen Canada, Shire Canada, Takeda Canada and Pfizer Canada and has consulted to Mylan Pharmaceuticals; he has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Shire Canada and Takeda Canada. RG has received consulting and speaking fees from AbbVie, Janssen, MSD, Ferring, Takeda and Baxter; and research grants from AbbVie. GJM has served as speaker or advisory board member for AbbVie, Angelini, Astellas, Danone, MSD, Falk Pharma, Ferring, Hospira, Janssen, Omega Pharma, Otsuka, Pharmacosmos, Pfizer, Sandoz and Takeda; as consultant for Janssen, MSD, Takeda and Omega Pharma; and has received research grants in the last 3 years from Menarini, AbbVie, and MSD. BS has served on advisory boards for Dann and Yakult North American Probiotic Council, Second Genome, Lilly and Enterome; and receives grant support from Janssen, Salix and GSK. MSS has received consulting and speaker fees from AbbVie, Amgen, Ferring, Janssen, Merck, Pfizer, Prometheus, Shire and Takeda; and research funding from AbbVie, Janssen, Prometheus and Takeda. IEK has served as a consultant and on advisory boards for AbbVie and MSD. CO is the principal investigator for Redhill Pharma. DPBM is a consultant for UCB, Jannsen, Merck and Second Genome. WR has served as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor and Yakult; as a consultant for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Vifor, Zyngenia and 4SC; as an advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zyngenia and 4SC; and has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik and MSD. GR has consulted to Abbot, Abbvie, Augurix, Boehringer, Calypso, FALK, Ferring, Fisher, Genentech, Essex/MSD, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillots, Vifor, Vital Solutions and Zeller; has received speaker's honoraria from Astra Zeneca, Abbott, Abbvie, FALK, MSD, Phadia, Tillots, UCB and Vifor; has received educational grants and research grants from Abbott/Abbvie, Ardeypharm, Augurix, Calypso, Essex/MSD, FALK, Flamentera, Novartis, Roche, Takeda, Tillots, UCB and Zeller. WK has received fees for advising from Dr. Falk Pharma GmbH, Ferring International, GA-Analysis; support for research from Dr. Falk Pharma GmbH and GA-Analysis; grants for lectures from Abbvie, Ardeypharm, Falk Foundation, Ferring Arzneimittel, GA-Analysis, Institut Allergosan, Nikkiso, Otsuka and Recordati. CT has served as a speaker for Dr. Falk Pharma, Tillotts Pharma, Ferring, MSD and AstraZeneca. SS has received consulting fees from AbbVie, Boehringer; Celltrion/Mundipharma, Jansen, Novartis, Merck, Pfizer/Hospira, Sanofi, Takeda and UCB; and speaking fees from AbbVie Ferring, Falk, Merck, Takeda and Shire. SD has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma and Vifor. WS reports grant support from Receptos, Exact Sciences, Amgen, the American College of Gastroenterology and the Broad Foundation; grant support and personal fees from Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, Pfizer and Nutrition Science Partners; and personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr. August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast, Shire, Ardelyx, Actavis, Seattle Genetics, MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, Qu Biologics, Toray Industries, Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx, Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen and the University of Western Ontario (owner of Robarts Clinical Trials). AG has served as a consultant for AbbVie, Janssen, Merck and Takeda; a speaker for Janssen; and received research and clinical programme support from AbbVie and Janssen. ST has received Grants/Research Support from AbbVie, IOIBD, Lilly, UCB, Vifor and Norman Collison Foundation; consulting fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chemocentryx, Cosmo, Ferring, Giuliani SpA, GlaxoSmithKline, Lilly, MSD, Neovacs, NovoNordisk, Norman Collison Foundation, Novartis, NPS Pharmaceuticals, Pfizer, Proximagen, Receptos, Shire, Sigmoid Pharma, Takeda, Topivert, UCB, VHsquared and Vifor; speaker fees from AbbVie, Ferring and Takeda. JP has received consultant fees from Abbvie, Boehringer Ingelheim, Celltrion, Galapagos, Genentech-Roche, Janssen, Pfizer, Takeda, TiGenix and Topivert; speaker fees from Abbvie, Celltrion, Janssen, MSD and Pfizer. JFC has served as a consultant or advisory board member for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Takeda and Theradiag; a speaker for AbbVie, Ferring, Takeda and Shire; receives research support from Abbvie, Janssen and Janssen, Genentech and Takeda; and has stock options for Intestinal Biotech Development and Genfit. SH is a consultant for AbbVie, Actavis, Amgen, Arena, Astellas Pharma Global, Astra Zeneca, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Catabasis, Cellgene, Celltrion, Cubist, Ferring, Forest Labs, Genentech, Glenmark, GSK, Hospira, Janssen, Lilly, Lutipold/American Regent, Meda, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Salix, Sanofi-Avantis, Seattle-Genetics, Seres Health, Shire, Takeda, Theradiag, Tigenex, UCB Pharma and VHsquared; does clinical research with Abbvie, Amgen, Genentech, GSK, Janssen, Lilly, Lutipold/American Regent, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Sanofi-Avantis, Takeda and UCB Pharma; is a speaker for AbbVie, Janssen and Takeda; and serves on a DSMB for Bristol Myers Squibb. LPB reports consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera and Samsung Bioepis; and lecture fees from Merck, Abbvie, Takeda, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi and HAC-pharma., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD., Methods: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives., Results: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS., Conclusions: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS.

Background and Aim: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD., Methods: Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory., Results: In total, 49% (200/408) of the patients had a 25-OH-D concentration <50 nmol/L, including 53% (122/230) of the Crohn's disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >100 mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency., Conclusions: Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.

Background & Aims: The prevalence of primary sclerosing cholangitis (PSC) among patients with inflammatory bowel disease (IBD) is unclear. Patients with IBD might be screened for PSC using magnetic resonance cholangiography (MRC). We aimed to estimate the frequency and distribution of MRC-detected lesions that indicate PSC in patients with IBD 20 years after their initial diagnosis and to identify clinical characteristics associated with these findings., Methods: We performed a follow-up analysis of a population-based cohort of 756 patients in South-Eastern Norway diagnosed with IBD from January 1, 1990 through December 31, 1993. Of these subjects, 470 attended a follow-up evaluation 20 years later in which they were offered routine clinical blood testing and ileocolonoscopy; 322 were screened by MRC (222 with ulcerative colitis and 100 with Crohn's disease). Two radiologists independently evaluated results from the MRC examinations., Results: In the MRC examination, 24 patients (7.5%) were found to have PSC-like lesions; only 7 of these patients (2.2%) were known to have PSC. One patient was initially missed and 1 had small-duct PSC, so the final prevalence of PSC was 8.1%. Extensive colitis, a high prevalence of colectomy, and chronic and continuous symptoms of IBD occurred in significantly more patients with suspected PSC than without PSC (P = .029, P = .002, and P = .012, respectively). Among patients with subclinical features of PSC, the MRC progression score for PSC increased when they were re-examined after a median 3.2 years (P = .046)., Conclusions: Using MRC analysis of patients with long-term IBD, we found the prevalence of PSC to be around 3-fold higher than that detected based on symptoms. Sixty-five percent of patients had subclinical PSC associated with progressive IBD, with no biochemical abnormalities and mild disease, based on radiology findings. PSC appears to progress in patients with subclinical disease, but long-term outcomes are not known., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Data on the long-term observation of health-related quality of life (HRQoL) in the inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis are scarce. Our aim was to determine HRQoL in a population-based cohort of patients with IBD 20 years after diagnosis and its association with demographic and clinical factors and to compare HRQoL of the cohort with that of the background population., Methods: Patients with IBD from a large population-based inception cohort (the IBSEN cohort) were invited to a prescheduled 20-year follow-up visit with a structured interview, a clinical examination, and laboratory tests. They completed the Short-Form 36 and the Norwegian Inflammatory Bowel Disease Questionnaire. The association between demographic and clinical factors and HRQoL was assessed with a linear regression analysis. Standardized scores were used to compare HRQoL in patients with that of the background population., Results: Of the still-living patients with IBD, 438 (73.1%) completed the HRQoL questionnaires. There were no differences in HRQoL scores between the patients with ulcerative colitis and those with CD. Women with CD obtained scores lower than those of men and women with CD in the background population. Current symptoms, increased disease activity, and not working were identified as factors associated with reduced HRQoL., Conclusions: In this population-based IBD cohort, the overall HRQoL scores obtained 20 years after diagnosis were relatively unaffected compared with the background population. However, women with CD had lower HRQoL scores than men with CD and women in the background population. Active disease and not working were the main factors associated with impaired HRQoL scores.

Background and Aims. No patient-reported outcome measures targeting pain have yet been validated for use in IBD patients. Consequently, the aim of this study was to test the psychometrical properties of the brief pain inventory (BPI) in an outpatient population with IBD. Methods. Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the BPI, as well as the Short-Form 36 (SF-36). Results. In total, 410 patients were included. The BPI displayed high correlations with the bodily pain dimension of the SF-36, as well as moderate correlations with disease activity indices. The BPI also displayed excellent internal consistency (Cronbach's alpha value of 0.91, regardless of diagnosis) and good to excellent test-retest values (intraclass correlation coefficient (ICC) 0.84-0.90 and Kappa values > .70). In UC, calculation of responsiveness revealed that only BPI interference in patients reporting improvement reached the threshold of 0.2. In CD, Cohen's d ranged from 0.26 to 0.68. Conclusions. The BPI may serve as an important supplement in patient-reported outcome measurement in IBD. There is need to confirm responsiveness in future studies. Moreover, responsiveness should ideally be investigated using changes in objective markers of inflammation.

Background: In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel., Methods: IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years., Results: The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM., Conclusion: In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

Background: The point prevalence estimates of anaemia in patients with inflammatory bowel disease (IBD) range between 6% and 74%. The variation is probably due to differences in the definition of anaemia and the study populations., Aim: To retrospectively determine the prevalence of anaemia at diagnosis and at the 1-, 5- and 10-year follow-ups in patients with IBD from a prospectively followed, population-based inception cohort (the IBSEN Study). To compare the prevalence of anaemia after a 10-year disease course with the prevalence of anaemia in the background population, and to assess clinical factors associated with anaemia at diagnosis and during follow-up., Methods: Newly diagnosed IBD patients were included in a population-based, prospective cohort. Follow-up was performed at 1, 5 and 10 years. All visits included clinical examinations and blood samples. Anaemia was defined according to the WHO., Results: A total of 756 patients (UC, n = 519 and CD, n = 237) were included; 48.8% of CD and 20.2% of UC patients were anaemic at diagnosis (P < 0.001). The proportion of patients with anaemia decreased during the disease course in all patients, except in women with CD. After 10 years of disease, the relative risk for anaemia was increased in all groups, except for women with UC. The variables associated with anaemia were generally unchanged during the disease course, and elevated CRP was the strongest predictor of risk., Conclusions: Anaemia was more common in CD than in UC. The prevalence of anaemia decreased during the disease course. Women with CD were at high risk for anaemia. Elevated CRP was independently associated with anaemia., (© 2013 John Wiley & Sons Ltd.)

Background: Identifying patients with Crohn's disease with increased risk of subsequent complications is essential for appropriate treatment. Based on exploratory analysis, we developed a prediction model for assessing the probability of developing advanced disease 5 and 10 years after diagnosis., Methods: A population-based cohort of 237 patients with Crohn's disease diagnosed from 1990-1994 was followed for 10 years. In the 5-year analysis, advanced disease was defined as having intestinal resection, progression in disease behavior, or need for thiopurines. The analysis was limited to patients with uncomplicated disease at diagnosis who were alive (n = 140), excluding those who were lost during follow-up (n = 8). For the 10-year analysis, advanced disease was defined as having surgery, excluding those who had surgery within the first 30 days (n = 7), those who died (n = 18), or were lost during follow-up (n = 22). Based on the best fitted multiple model, the probabilities of advanced disease were computed for selected baseline levels of the covariates and the results were arranged in a prediction matrix. Except for ASCA, all predictors were measured at diagnosis., Results: ASCA status, disease location, age, and need for systemic steroids were included in the 5-year prediction matrix. The probabilities of advanced disease during this period varied from 8.6% to 92.0% depending on the combination of predictors. The 10-year matrix combined ASCA status, disease behavior, age, and need for systemic steroids; the probabilities of advanced disease ranged from 12.4% to 96.7%., Conclusions: Our prediction models revealed substantial differences in the probability of developing advanced disease in the short and intermediate course of Crohn's disease, suggesting that a model-based prediction matrix is useful in early disease management.

Objective: The prevalence of anemia in inflammatory bowel disease (IBD) has been broadly described. The recurrence, type and burden of anemia remain unenlightened. The primary objective was to describe this. The secondary objective was to evaluate the implementation of European guidelines., Materials and Methods: This longitudinal follow-up study included 300 IBD outpatients from six centers in Scandinavia. Patients were enrolled in a research cohort, in which each center included 5% of their IBD cohort. The study was prospectively planned, while data were retrospectively collected. The burden of anemia was calculated as number of months with anemia. A Markov model was used to calculate the probabilities of transitioning between stages. The European guidelines were used as the standard for anemia management., Results: Anemia affected > 50% of IBD outpatients during the 2-year observation period. Totally, 20% of the total observation time was spent in anemia. Over the 7200 months of observation, anemia was found in 1410 months. The most frequent type was combined anemia (63%). Combined anemia covers both anemia of chronic disease (ACD) and iron-deficiency anemia (IDA). Pure ACD was present in 21% of burden time, while pure IDA was present in 16% of burden time. The European guidelines have mainly been implemented., Conclusion: Anemia affected a majority of the IBD outpatients. One in five months, the patients were anemic. Anemia related to inflammation dominated the different types of anemia. Pure IDA was found in for 16%. These findings, despite a fair implementation of guidelines.

Objective: To compare the work disability (WD) rate in inflammatory bowel disease (IBD) patients 10 years after disease onset, with the WD rate in the background population,and to assess whether clinical or demographic factors in the early disease course could predict WD after 10 years disease., Design: A large, population-based inception cohort (the Inflammatory Bowel in South Eastern Norway cohort) was prospectively followed up at 1, 5 and 10 years after diagnosis. At the 10-year follow-up data on WD were collected. Data on disability pension (DP) in the background population were retrieved from public databases. We calculated overall and age-standardised relative risks (RR) for DP. Logistic regression analysis was used to examine predictive factors., Results: A total of 518 patients completed the 10-year follow-up (response rate 83.5%). The overall disability rate in the IBD population was 18.8%, and the RR was 1.8 (95% CI 1.4 to 2.3) for ulcerative colitis (UC) and 2.0 (95% CI 1.4 to 2.7) for Crohn's disease (CD). The RR for DP was highest in patients aged below 40 years while patients aged over 60 years had no increased RR. Steroid treatment at the 1-year follow-up predicted WD after 10 years disease in both CD and UC. In UC, increased C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) at diagnosis, early colectomy, and more than two relapses during the first year of the disease also predicted WD., Conclusion: Ten years after disease onset IBD patients had an increased RR for DP as compared with the background population. The youngest patients had the highest RR. Markers of severe disease course predicted WD.

Objective: To determine the proportion of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) and to identify demographic and clinical factors that are associated with CAM use., Material and Methods: In this cross-sectional study design, patients with confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease (CD), and ≥18 years old, attending outpatient clinics at 14 hospitals in Norway were eligible to complete questionnaires including demographics, clinical variables, and the International CAM Questionnaire (I-CAM-Q)., Results: Of 460 patients included in the study, 430 had evaluable questionnaires (response rate 93%). Forty-nine percent (95% CI: 44-54) had used some type of CAM within the past 12 months. CAM services were utilized by 27% (95% CI: 23-31) of the patients, 21% (95% CI: 16-23) reported use of CAM products, and 28% (95% CI: 23-31) used CAM self-help practices. The most common pattern of CAM use was to combine CAM services and CAM products. Significantly, more UC patients (56%) than CD patients (44%) reported CAM use, p = 0.03. In UC, only the presence of at least one comorbid condition was directly related to CAM use. In CD, being a woman, being aged 31-50 years, having a higher education level, and experiencing adverse drug reactions from IBD medication were factors independently associated with the use of CAM., Conclusion: Use of CAM was common among IBD patients attending outpatient clinics. Both demographic and clinical factors were associated to CAM use, but the factors differed in their significance for UC and CD.

Objective: Specialist nurses have become increasingly involved in the management of Inflammatory Bowel Disease (IBD). The objectives of this study were to investigate the impact of nurse-led versus conventional follow-up on patient outcomes, such as quality of life, worries and time from relapse to start of treatment., Methods: Patients completed the Short Form 36 (SF-36), Inflammatory Bowel Disease Questionnaire (N-IBDQ) and the Rating Form of IBD Patient Concerns (RFIPC) at baseline and after 1 year. Socio-demographic and clinical variables were obtained at V1 and V2. In addition the amount of e.g., relapses, hospitalisations, time from relapse to start of treatment, sick-leave, unscheduled visits or telephone calls was recorded during the follow-up period., Results: A total of 140 patients were included; ulcerative colitis (UC) n=92, Crohn's disease (CD) n=48, mean age 46.9 and 40.0 years old, respectively. One hundred and thirty three patients attended the follow-up after 1 year. After 1 year there were no differences between the groups in relation to quality of life, worries, amount of relapse, sick-leave, hospitalisations or surgery. Participants in nurse-led follow-up had a significantly (p<0.05) shorter interval from the start of a relapse to the start of treatment., Conclusions: Nurse-led follow-up of IBD patients produces PRO results comparable to that of gastroenterologists and may shorten the interval from the beginning of a relapse to the start of treatment., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Data on the long-term effects of Crohn's disease (CD) on health-related quality of life (HRQoL) is scarce. We aimed to determine the HRQoL in CD patients 10 years after disease onset, to compare the results to the general population and to identify variables that could affect HRQoL., Methods: CD patients from a population-based inception cohort (the IBSEN Study) met at a prescheduled ten-year follow-up. In addition to a structured interview, review of hospital records, clinical examination, laboratory tests and ileocolonoscopy, they completed a patient-reported questionnaire including the Short Form 36 (SF-36) and the Norwegian Inflammatory Bowel Disease Questionnaire (N-IBDQ). The SF-36 scores were compared to scores from the general population using one-sample t-tests. Standardized scores were calculated and interpreted according to Cohen's effect size index. The associations between relevant clinical and demographic factors and HRQoL were examined through linear regression analyses., Results: Ninety-nine patients completed the HRQoL questionnaires (response rate 86%). Median age 39 years, 42% women. Compared to the general population the patients reported significantly lower SF-36 scores on the general health and vitality dimensions. IBDQ total scores were in line with scores of patients in remission. Except for current symptom severity no clinical parameters affected HRQoL scores. Work status and sick leave affected HRQoL negatively., Conclusions: In this chronic stage of CD, reduced general health and vitality scores need attention while reductions in disease specific HRQoL seem to be less predominant., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Hospitalisation and surgery are considered to be markers of more severe disease in Crohn's disease. These are costly events and limiting these costs has emerged as one rationale for the cost of expensive biologic therapies. The authors sought to review the most recent international literature to estimate current hospitalisation and surgery rates for Crohn's disease and place them in the historical context of where they have been, whether they have changed over time, and to compare these rates across different jurisdictions. It is in this context that the authors could set the stage for interpreting some of the early data and studies that will be forthcoming on rates of hospitalisation and surgery in an era of more aggressive biologic therapy. The most recent data from Canada, the United Kingdom and Hungary all suggest that surgical rates were falling prior to the advent of biologic therapy, and continue to fall during this treatment era. The impact of biologic therapy on surgical rates will have to be analysed in the context of evolving reductions in developed regions before biologic therapy was even introduced. Whether more aggressive medical therapy will decrease the requirement for surgery over long periods of time remains to be proven.

Background and Aims: The use of complementary and alternative medicine (CAM) has been increasing in recent decades. Our aim was to determine the proportion of CAM use among patients with inflammatory bowel disease (IBD) in a longitudinal, population-based cohort and to identify predictive factors for CAM use., Methods: The Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population-based IBD cohort that has been followed prospectively for 10 years. The ten-year follow-up was conducted from 2000 to 2004 and included a questionnaire regarding CAM, a structured interview, a review of hospital records, a clinical examination, laboratory tests, and an ileocolonoscopy., Results: Of the 620 patients evaluated at the ten-year follow-up, 517 (84%) completed the CAM questionnaire, 353 had ulcerative colitis (UC), 164 had Crohn's disease (CD), and 50% were male. Thirty percent reported the use of CAM at some point since their IBD diagnosis, and 7.5% reported current CAM use. More CD patients than UC patients reported CAM use (38% vs. 27%, respectively; p=0.01). Younger age, female gender, and higher education level predicted CAM use in UC, whereas younger age was the only predictor of CAM use in CD. Thirty-six percent of the CAM users were mostly satisfied or very satisfied with the treatment., Conclusion: One third of the patients in this population-based cohort had used CAM at some point during a ten-year disease course, but only 7.5% reported current CAM use. CAM use was more common in the CD than in the UC patients. Only socio-demographic factors, such as age, gender and education, predicted CAM use., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: The aims of this study were to explore the influences of familial, maternal, and paternal inflammatory disease (IBD) on perinatal outcomes in the offspring and the risk for development of IBD related to perinatal factors., Methods: Eighty-five patients with Crohn's disease (CD) and 86 with ulcerative colitis (UC) were included from a population-based incidence study enrolled 1990-1994. Family and birth records of these patients, as well as of their 207 infants, were drawn from the Norwegian Medical Birth Registry, established in 1967, and compared with the national birth cohort from the same period., Results: Maternal (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.36, 3.39) and paternal IBD (OR = 3.02, 95% CI: 1.82, 5.01) influenced the risk of preterm birth (<37 weeks), which further increased if the affected parents had a first-degree relative with IBD (OR = 4.29, 95% CI: 1.59, 11.63). Maternal CD was associated with lower birth weight in the offspring (crude difference: 271.79 g, 95% CI: 87.83, 455.77, versus controls). Maternal UC increased the risk of perinatal bacterial infection in the offspring (OR = 6.03, 95% CI: 2.03, 17.91). IBD patients (2.3%) were less likely to be delivered by cesarean section than controls (8.1%) (OR = 0.27, CI: 95%: 0.10, 0.73)., Conclusions: Familial, maternal, and paternal IBD were linked to preterm birth, which might be explained by genetic mechanisms. The present protective effect of cesarean sections needs further clarification in future studies.

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

In this systematic review we focus on the current use of and knowledge on health related quality of life in unselected, population-based IBD cohorts. We made a systematic literature search and included for comprehensive review papers that described a population-based cohort and that used validated HRQoL instruments. We show that even studies defined by the authors as population-based do not always meet the criteria set for being population-based. The heterogeneity of the study populations we have reviewed emphasizes that "population-based" must be defined very meticulously and that study populations need to be scrutinized with regard to all characteristics of the cohort before one can compare their results. Different definitions of study populations as population-based affect outcomes. We also show that use of the same HRQoL questionnaires does not guarantee comparable results as there are several different versions of the questionnaires, the different translations are not always comparable and at last there are several methods of computing and presenting the data. Detailed accumulation of knowledge and thorough meta analyses is therefore difficult hence we find it necessary to raise a discussion on the need of standardization in this field of research and we make some simple recommendations on factors we find important.

Background: The aim was to compare clustering of time at diagnosis and phenotype of inflammatory bowel disease (IBD) between affected parents and children and to explore generational differences in age at diagnosis (AAD) as well as the concordance of clinical characteristics., Methods: Eighty-four affected pairs from 45 families were included from 5 counties in southeastern Norway between August 2003 and December 2006; 43 were sib-sib pairs and 39 parent-child pairs. Clinical data were obtained by phone interviews and by hospital records., Results: The difference in median AAD was 17.0 years (P < 0.001) and 2.0 years (P = 0.29) in parent-child and sib-sib pairs, respectively. When the time interval between diagnosis in parent and child was split into 2 groups, below and above 5 years, 64% of pairs with ulcerative colitis (UC) offspring were diagnosed within 5 years, compared to 24% of pairs with Crohn's disease (CD) offspring (odds ratio [OR] = 5.7, 95% confidence interval [CI]: 1.4, 23.8). Concordance for smoking habits was low in 26 pairs with mixed disease (κ = 0.15), whereas patients with CD tended to be current smokers., Conclusions: Most of the children acquire their disease at an earlier time in life compared to their parents, suggesting genetic anticipation. The time interval between diagnosis of the parents and offspring was lower when the offspring developed UC compared to CD, which might reflect the influence of shared environment on the generational difference in AAD in UC families. This study confirmed the effect of smoking habits on IBD phenotype., (Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.)

Background and Aims: C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome., Methods: CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis., Results: Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03)., Conclusions: CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.

Inflammatory bowel disease refers to a group of chronic diseases of unknown etiology related to both genetic and environmental factors. In this 1990-1993 study, the authors investigated associations between the content and quality of drinking water and the incidence of inflammatory bowel disease. They used data from a population-based cohort recruited in southeastern Norway and a registry of water quality derived from Norwegian waterworks that contained measurements of iron, aluminum, acidity (pH), color, turbidity, and coliform bacteria. The authors found that risk of developing inflammatory bowel disease, including ulcerative colitis and Crohn's disease, was associated with high iron content. The relative risk of developing inflammatory bowel disease increased by 21% (95% confidence interval: 9, 34) when the iron content in the drinking water increased by 0.1 mg/L. They found no association between the diseases and aluminum in the water, color of the water, and turbidity of the water. The authors suggest that the observations can be explained by 2 mechanisms. First, high iron concentration works as a catalyst for oxidative stress, which will cause inflammation and/or increase the rate of cell mutations. Second, iron content stimulates the growth of bacteria and increases the likelihood of inappropriate immune responses in genetically predisposed individuals.

Background & Aims: Most studies concerning the clinical course in CD are retrospective or based on selected patient groups. Our aim was to assess the course of CD in a prospective population-based follow-up study and to identify possible prognostic risk factors for complications on the basis of information obtained at initial diagnosis., Methods: From 1990-1994, a population-based cohort of 843 new cases of inflammatory bowel disease was recruited in South-Eastern Norway. The cohort was systematically followed up at 1, 5, and 10 years after diagnosis., Results: Of 237 patients classified as CD, 197 completed the 10 years of follow-up, 18 died, and 22 were lost to follow-up. The cumulative relapse rate during the first 10 years was 90% (95% confidence interval, 86%-94%), and the cumulative probability of surgery was 37.9% (95% confidence interval, 31.4%-44.4%). Terminal ileal location (P < .001), stricturing (P = .004), penetrating behavior (P < .001), and age younger than 40 years (P = .03) at diagnosis were independent risk factors for subsequent surgery. A total of 53% (n = 105) of the patients had developed stricturing or penetrating disease at 10 years. A large proportion of patients (44%) were in clinical remission during the last 5 years of follow-up., Conclusions: The prognosis for CD seems better than previously reported. The probability of surgery was low, and fewer than expected developed complicated disease behavior. Nevertheless, the cumulative relapse rate of 90% and the finding of prognostic risk factors for subsequent surgery might call for attention to early effective medical treatment strategies.

Background: Colorectal cancer is a complication of longstanding inflammatory bowel disease. The association between cancer and inflammation is best documented in ulcerative colitis, but an increased risk of cancer is also found in patients with Crohn's disease. Surveillance with colonoscopy is commonly used to detect dysplasia and early cancer in patients with in ulcerative colitis. There has been an increased focus on chemoprevention during the last decade., Material and Method: This paper is based on literature retrieved through non-systematic searches of the PubMed and Cochrane databases., Results and Interpretation: Several recent studies indicate that the incidence of colorectal cancer in patients with ulcerative colitis is lower than previously shown; in some population-based studies it does not exceed that in the general population. Extensive use of 5-aminosalicylates (5-ASA) explains a substantial part of the declining risk. The effect of surveillance colonoscopy has not been documented through prospective and randomized studies. Several studies have shown an increased risk of colorectal cancer and cancer in the small bowel in patients with Crohn's disease. No evidence supports that treatment with 5-ASA reduces the risk of colorectal cancer in patients with Crohn's disease, or that regular use of surveillance colonoscopy reduces the risk of cancer or mortality in patients with longstanding chronic inflammatory disease.

Background: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD., Methods: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated., Results: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care., Conclusions: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.

Background: There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD)., Aim: To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification., Methods: All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990-1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy., Results: Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period., Conclusions: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.

Objective: Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis., Material and Methods: A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method., Results: Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South., Conclusions: In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

Background and Aim: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort., Methods: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files., Results: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype., Conclusion: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Background: In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning., Aims: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis., Methods: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease., Results: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89))., Conclusions: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of F(ST), indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.

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

Objective: To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors., Materials and Methods: A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization., Results: Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries., Conclusions: This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.

Background: We compared health-related quality of life (HRQOL) in a population-based cohort of Norwegian patients with inflammatory bowel disease (IBD) with a normal reference population by means of the short form-36 (SF-36) questionnaire, including the effect of age, sex, educational status, and symptom severity and the psychometric properties of the questionnaire., Methods: The SF-36 was self-administered and was answered by the patients at the hospital at 2 occasions that were 6 months apart., Results: Five hundred fourteen patients with IBD were eligible for analysis: 348 with ulcerative colitis (UC) and 166 with Crohn's disease (CD). The comparison group consisted of 2323 Norwegian people. The dimension scores for SF-36 were significantly lower in 6 of 8 dimensions for patients with UC and in 7 of 8 dimensions for patients with CD than for the reference population. In both patients with UC and patients with CD, we found lower scores in elderly patients, which also was found in the background population. Women scored lower than men in all dimension scores. In both patients with UC and patients with CD, there was a statistically significant reduction in HRQOL score with increasing symptoms. The SF-36 has satisfactory reliability and discriminant ability for scores for all dimensions in both patients with UC and patients with CD. However, when measuring responsiveness, the figures were generally low. This finding, together with the high ceiling effects, may indicate that the SF-36 has limitations regarding detecting deterioration or improvement over time., Conclusion: We have shown that HRQOL in a Norwegian population-based cohort of patients with IBD, measured with the SF-36, is lower than that of a Norwegian reference population. In general, the SF-36 was found to have satisfactory psychometric properties in this IBD population.

Background: Health-related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow-up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow-up study from 1990 to 1994 (the IBSEN study)., Methods: All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed., Results: Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups., Conclusion: IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.