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Background The risk of surgery remains high both among patients with ulcerative colitis (UC) and patients with Crohn’s disease (CD) with a cumulative risk of subtotal colectomy with ileostomy and diverted rectum of 7.5% after 5 years in UC and a similar risk in CD. Ileostomy with diverted rectum after colectomy may be permanent, or the patient can undergo restorative surgery with ileo-rectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). Risk of rectal cancer in this patient population remains uncertain. We performed a nationwide population-based Danish study of rectal cancer (RC) risk after subtotal colectomy. Methods Through the Danish Civil Registration System, a source population of all individuals 15 years or older living in Denmark between 1978 and 2018 was retrieved. By use of the unique personal identification number given to all citizens at birth, this source population was linked to the Danish National Patient Registry (NPR) in order to identify all patients with inflammatory bowel disease (IBD). Patients with a diverted rectum, IRA or IPPA after colectomy were also identified with NPR. Cases of RC were identified in the Danish Cancer Registry. Patients with IBD were followed from the date of surgery until cancer, emigration, death or end of the study. The risk of RC in patients with diverted rectum was assessed using Cox regression analyses, as compared to the background population as well as to subjects with IBD without subtotal colectomy. Results RC occurred in 42 (0.9%) of 4931 patients after subtotal colectomy with diverted rectum, compared to 209 (0.4%) of 49,251 in the matched IBD cohort with no colectomy and 941 (0.4%) of 246,550 in the matched background population. In the IBD and subtotal colectomy population 11 (26%) of the 42 cases were in patients diagnosed with CD and 31 (74%) were in patients with UC. The hazard ratio (HR) for RC in IBD patients with diverted rectum vs. matched IBD patients without colectomy (adjusted for IBD type and sex) was 0.80 (95% CI 0.29, 2.17) during the first 10 years of follow-up and 7.93 (95% CI 5.48, 11.48) 10 years or more after colectomy. Likewise, the HR for RC in IBD patients with diverted rectum compared to the matched background population was 0.85 (95% CI 0.32, 2.28) during the first 10 years of follow-up and 10.25 (95% CI 7.36, 14.28) 10 years or more after colectomy. Conclusion In our nationwide population-based cohort study covering years 1978–2018 we observed an 8 to 10-fold increased risk of RC of the diverted rectum 10 years after colectomy.These data suggest a need for developing a specific surveillance strategy for this group of IBD patients.

Background The impact of discontinuing vs. continuing thiopurines at anti-TNF initiation in thiopurine experienced patients with inflammatory bowel disease (IBD) is unclear. Methods We used the nationwide Danish registers to establish a national cohort of patients with IBD who received thiopurines prior to initiating anti-TNF during 2003–2014. We compared patients who discontinued vs. continued thiopurine within 90 days of anti-TNF initiation. Our primary outcome was a composite of any clinical event: corticosteroids, hospitalisation, surgery, or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Analyses were adjusted for sex, diagnosis-age, IBD-subtype, disease duration, calendar year, pre-anti-TNF thiopurine duration, and past disease severity including hospitalisations the past year, surgery past 5 years, and corticosteroid use the past year. Results Of 6998 anti-TNF exposed, 1602 patients (Crohn’s disease, n = 1000, ulcerative colitis, n = 602) received thiopurines prior to anti-TNF. Of these, 489 (44%) received thiopurines for more than 180 days. At anti-TNF initiation, 503 patients discontinued thiopurines and were followed for a median 3.54 years and 1099 continued thiopurines with a median follow-up of 3.92 years. Discontinuing thiopurines at anti-TNF initiation statistically significantly increased the risk of the composite outcome (aHR 1.25; 95% CI 1.09 to 1.45). Analyses of the individual outcomes revealed a statistically significantly increased risk of later corticosteroid use in thiopurine discontinuers (aHR 1.31; 95% CI 1.11 to 1.56), but no increased risk of the remaining outcomes. IR; incidence rate, HR; hazard ratio, CI; confidence interval, IBD; inflammatory bowel disease. P-value is the test of interaction between the variable and the treatment groups. Conclusion In our nationwide cohort study of patients with IBD, we found that continuing thiopurines after anti-TNF initiation impacted the outcome favourably, especially regarding corticosteroid use. Further studies are warranted to investigate this central clinical question.

Background Biologic treatment has revolutionised the treatment of inflammatory bowel diseases (IBD) and has been shown to reduce surgery and hospitalisation rates in patients with severe disease. Up to one-third of patients do not respond to first-line biologic drugs and another third loses response with time. This highlights an unmet need for optimising the use of biologics and for predicting treatment response to biologics. We present the initial recruitment stages and experimental pipeline for The Danish IBD Biobank which aims to identify predictive biomarkers of response and disease course in patients with IBD who receive biologics. Methods The Danish IBD Biobank constitutes a multicenter prospective cohort study aiming to include 840 biological-naïve adult patients with IBD who initiate biologic therapy in a three-year period from May 2019 and onwards. Primary outcomes are the occurrence of primary non-response (PNR) evaluated at week 14–16 and loss of response (LOR) evaluated during the entire follow-up. Patients will be followed with clinical data for at least one year or until May 2022 and sampled for blood, stool and intestinal tissue during the first year of treatment. Blood and stool samples are collected at each visit for biologic treatment and upon change in drug type, dosing or discontinuation. Intestinal tissue is sampled whenever an endoscopy is performed and after one year of treatment (Figure 1). Results As of 15 November 2019, 132 patients have been recruited to the cohort. Biologic treatment was indicated due to acute severe ulcerative colitis (UC) or chronic active UC in 13% and 43% of patients, respectively, while 38% and 6% received treatment for luminal Crohn’s disease (CD) and perianal CD. In accordance with national guidelines issued by the Danish Medicines Council, infliximab was the most commonly used first-line drug (98%), followed by vedolizumab (2%) and adalimumab (0.8%). Among 68 patients who have completed induction therapy so far, PNR occurred in 35% (62% UC, 38% CD). Among those with PNR, 50% switched class, 21% discontinued treatment and 29% underwent surgery. Blood and stool samples and intestinal biopsies are stored in a biobank awaiting characterisation of RNA and protein expression using multiplex immunoassay, 16S and Illumina sequencing, and characterisation of mucosal gene and protein expression (Figure 2). Conclusion The Danish IBD Biobank project aiming to identify predictive transcriptomic, microbial and proteomic biomarkers associated with treatment response and outcomes to biological therapy in a prospective cohort of biological-naïve IBD patients has been successfully launched. Funding This study is funded by an unrestricted grant from Takeda A/S and public fund hosted by Hvidovre Hospital.

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

Current data indicate a change in the epidemiology of inflammatory bowel diseases. The disease has become more widespread and the rise in the incidence has been reported in all age groups including early childhood and according to recent data also the elderly population. Some earlier studies have suggested that the phenotype and natural history of the disease may be different according to age of onset. Recently the importance of age at onset was reported in two population-based studies from France and Hungary including both paediatric and adult onset inception cohorts. Early onset disease was associated with more frequent disease extension in both Crohn's disease and ulcerative colitis and in most but not all studies with higher frequency of complicated disease behaviour. This is also accompanied by striking differences in the medical management with earlier and more prevalent (2–3-fold) use of immunosuppressives and to some extent biologicals in patients with early compared to elderly-onset disease, especially in Crohn's disease. However, the results of population-based studies on impact of age on surgery rates in Crohn´s disease as well as ulcerative colitis are conflicting. Furthermore, published data indicate that relative but not absolute risk of developing cancer and mortality is higher in patients with an early onset disease. Critical reviews that focus on the importance of age at onset in inflammatory bowel disease are rare. Therefore, the aim of this review is to describe the differences in epidemiology, clinical characteristics, and natural history of paediatric and elderly-onset inflammatory bowel disease based on studies performed in general population.

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Inflammatory bowel diseases (IBD) are chronic disabling gastrointestinal disorders impacting every aspect of the affected individual's life and account for substantial costs to the health care system and society. New epidemiological data suggest that the incidence and prevalence of the diseases are increasing and medical therapy and disease management have changed significantly in the last decade. An estimated 2.5–3million people in Europe are affected by IBD, with a direct healthcare cost of 4.6–5.6bn Euros/year. Therefore, the aim of this review is to describe the burden of IBD in Europe by discussing the latest epidemiological data, the disease course and risk for surgery and hospitalization, mortality and cancer risks, as well as the economic aspects, patients' disability and work impairment.

Background The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients. Methods A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003–2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression. Results Being breastfed > 6 months (OR, 0.50; 95% CI, 0.23–1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31–0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12–0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07–4.03) and polio (OR, 2.38; 95% CI, 1.04–5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15–10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC. Conclusion Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.