Abstract Background Low-dose azathioprine in combination with allopurinol (LD-AZA/ALLO) is a widely used treatment option in inflammatory bowel disease (IBD). Data on pregnancy and birth outcomes from exposure to combination therapy are sparse. The aim of this study was to provide data on safety and risk for adverse pregnancy and birth outcomes in women with IBD treated with LD-AZA/ALLO at the Gastrounit, Hvidovre Hospital, Copenhagen. Methods The study was a retrospective single center study. Inclusion criteria were established IBD diagnosis and treatment with LD-AZA/ALLO (AZA 50-75 mg/ ALLO 100 mg) during conception and pregnancy between 2013-2023. Data was collected from electronic medical charts and by questionnaire to all included women. Data registered was; demographics, diagnosis, disease characteristics, disease activity, IBD medications and number of pregnancies. Pregnancy outcomes were neonatal characteristics, obstetric complications, lactation and congenital malformations, disease, infections and admission to the hospital during the first year of life. Results In all, 44 women with 62 pregnancies (one twin pregnancy) and 59 live births were included. There were 1 spontaneous and 3 provoked abortions due to genetic disorders (1 trisomy 21 and 2 spinocerebellar ataxia). Obstetric complications were present in 8 (13%) pregnancies, (1 pre-eclampsia, 1 HELLP syndrome, 6 hypertension and/or gestational diabetes mellitus). 7 (11%) women had an IBD flare during pregnancy, none resulting in obstetrical complications. 5 (9 %) children were born prematurely, 4 (7 %) had low birth weight. No congenital malformations were reported. One child was born with facial nerve paralysis and later diagnosed with hyper-IgD syndrome. 8 (14 %) were admitted to neonatal ward (hours to days), mainly due to immature lungs. During the first year of life, one child was admitted to the hospital due to COVID. One child was suspected to have an immune defect, but all symptoms and biochemical abnormalities resolved and interpreted as side effect to LD-AZA/ALLO. 5 children (9%) were treated with antibiotics due to minor infections. In total 84 % of the children were breastfed during LD-AZA/ALLO treatment. Conclusion In this large single center experience with 62 pregnancies in women treated with LD- AZA/ALLO, no malformations or indications of increased risk of complications of pregnancy and birth were observed. The majority of children were breastfed and no serious signals or complications were reported first year of life. Treatment with LD-AZA/ALLO during pregnancy and breastfeeding seems safe.

Abstract Background The pharmacokinetic (PK) profile of vedolizumab during pregnancy is not fully characterised, though concentrations have been reported to drop1.To minimise transplacental transfer, discontinuation in the 3rd trimester has been suggested, but this may lead to flare in IBD in pregnancy and postpartum2. This study aimed to characterise changes in vedolizumab PK in pregnancy using mathematical modelling and to explore dosing scenarios to guide decisions on 3rd-trimester dosing. Methods A multicenter, prospective, observational study was conducted recruiting pregnant women with IBD receiving vedolizumab. Pre-pregnancy patient characteristics were recorded. Vedolizumab dosing regime, vedolizumab trough concentrations, presence of vedolizumab antidrug antibodies, clinical and biochemical data were assessed before vedolizumab administrations and at delivery. Vedolizumab data were analysed using a nonlinear mixed-effects PK modelling approach. As a starting point for pregnancy model development, a PK model of vedolizumab from the drug development program based on 2554 patients was used3. Employing the final model, different dosing scenarios were simulated. Underexposure to vedolizumab was defined as concentrations ≤ 10 mg/L4. Results From 39 pregnant women, 136 vedolizumab measurements were analysed. The developed PK model comprised 2 disposition compartments with linear and target-mediated elimination pathways, and it incorporated the impact of pre-pregnancy patient characteristics e.g. albumin levels, body weight and disease status, as well as a gestation-dependent decrease in albumin due to plasma expansion and additional increase in elimination in the 3rd trimester. Trough vedolizumab concentrations were observed to drop during pregnancy, especially in the 3rd trimester (Figure 1: dosing interval of every 8 weeks). The median trough concentrations (pre-pregnancy albumin of 40 g/L) decreased by 10%, 20%, 30% and 40% until weeks 10, 23, 32 and 36 of gestation, respectively. Vedolizumab concentrations were lower for patients with lower pre-pregnancy albumin. Changes in the vedolizumab PK profile in pregnancy for two dosing scenarios are shown in Figure 2. If the dose scheduled in the 3rd trimester is skipped, the duration of the vedolizumab underexposure is prolonged in ≥ 50% of the patients, depending on the delivery time, to 6-10 weeks (Figure 2a) and 2-6 weeks (Figure 2b). Conclusion Vedolizumab concentrations progressively decrease in pregnancy, especially in the 3rd trimester, resulting in underexposure to the drug if not dosed throughout pregnancy, including the last trimester. These results underscore the importance of continuing vedolizumab throughout pregnancy to maintain disease remission in pregnancy and post-partum. References 1.Prentice R, Flanagan E, Wright EK, et al. Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero. Clin Gastroenterol Hepatol. Published online March 2024:S1542356524002520. doi:10.1016/j.cgh.2024.02.0252. 2.Torres J, Chaparro M, Julsgaard M, et al. European Crohn’s and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis. 2023;17(1):1-27. doi:10.1093/ecco-jcc/jjac1153. 3.Rosario M, Dirks NL, Gastonguay MR, et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn’s disease. Aliment Pharmacol Ther. 2015;42(2):188-202. doi:10.1111/apt.132434. 4.Verstockt B, Mertens E, Dreesen E, et al. Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients. J Crohns Colitis. 2020;14(3):332-341. doi:10.1093/ecco-jcc/jjz151.

Abstract Background The disease course of Ulcerative Colitis (UC) remains unpredictable. While some patients experience years of remission, others experience frequent flares, hospitalization, and surgery. The PRESAGER study aims to develop decision models to predict UC disease activity. In this preliminary analysis, we created a logistic regression model to identify predictors of remission. Methods UC patients with disease activity (Mayo endoscopic score [MES] ≥ 1) were recruited into the study. Demographic data, disease history, IBD Disability Index (IBD-DI), biopsies, and blood samples were collected at inclusion. Eight weeks later, patients were followed up with IBD-DI, blood samples, and an optional sigmoidoscopy. Medications taken before inclusion and during the follow-up period were recorded. Symptomatic or endoscopic remission was noted depending on if patients opted for follow-up endoscopy. Using multivariate logistic regression, we examined the association between inclusion data and disease remission. Stepwise model selection by Akiake information criterion (AIC) was used to create a logistic regression model with the most relevant predictors. Results were reported as odds ratios (ORs), 95% confidence intervals (CIs) and p-values. AI was used for writing inspiration and help with R coding, and no work was copied directly from an AI source. Results As of September 2024, 250 patients were included in the study. 182 (73%) patients had completed eight-week follow-up with IBD-DI and blood samples, and 72 (29%) patients had completed the eight-week follow-up sigmoidoscopy. At inclusion, left-sided colitis and moderate disease activity were most common. When looking at medications taken within 14 days of inclusion, 66% of patients used mesalazine suppositories and 61% used oral mesalazine or sulfasalazine (Figure 1). Other treatments included mesalazine foam/enemas (30%), oral corticosteroids (26%), immunomodulators (18%), and biologics (14%). A multivariate logistic regression model showed that older age and higher IBD-DI scores significantly reduced the likelihood of remission, whereas a longer disease duration was linked to a greater likelihood (Table 1). Surprisingly, calprotectin levels above 500 was associated with increased likelihood of remission compared to levels below 250. Additionally, patients with moderate disease activity had a greater likelihood of remission than those with mild activity, likely due to the increased use of corticosteroids and biologics in these cases. Conclusion Older age and higher disability scores significantly reduced the likelihood of remission for UC patients, while longer disease duration, moderate disease activity, and high calprotectin increased the likelihood.

Abstract Background Endoscopic ulcerative colitis (UC) severity classification shows high interobserver variance. Our prior study proved AI matches central reading scoring still images. To be clinically useful, assessing longer segments is vital. Our aim: a new model for real-time or video-based severity evaluation and demonstrate the supporting value it might offer. Methods Data was Mayo Endoscopic Subscore (MES)-scored using 2561 images and 53 videos from 645 patients to train a convolutional neural network. Through open-set-recognition, the model differentiated scoreable from unscoreable endoscopy sections. The validation included 140 videoclips from 44 UC patients. Six IBD-experts and 16 non-IBD experts independently rated these clips, with the majority IBD-expert score serving as ground truth. We assessed its value as a second opinion for non-IBD experts and conducted an alpha test with real-time endoscopic support on a real-world patient. Results The model achieved an overall accuracy of 0.82 and 0.84 for MES 0, 0.81 for MES 1, 0.72 for MES 2, and 0.96 for MES 3. No significant distinction between individual experts or ground truth vs. the AI model was observed (figure 1). When employed as a trigger for second opinions, non-IBD experts' performance improved by 10% (table 1). On average, 26-32 % (range on an individual level: 17-39 %) of the time (depending on the evaluated seniority) the framework disagreed with the primary physician. In those cases, the model was correct in an average of 57-59 % (range on an individual level: 33-76%), and the second physician’s opinion was correct in an average of 64-70 % (range on an individual level: 60-77%) of the time according to the ground truth. The alpha test successfully integrated the model into the endoscopic column for real-time classification. It accurately discerned MES 0 and MES 1 frames, aligning with the endoscopist's assessment. Conclusion Our innovative AI model exhibits significant potential for enhancing UC severity classification accuracy, rivalling IBD-experts and notably improving non-specialists' proficiency. It is designed for clinical implementation and has demonstrated clinical feasibility in an alpha test. Figure 1: Table 1:

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

Abstract Background Evaluation of endoscopic disease severity is a key component in the management of ulcerative colitis (UC) patients. However, endoscopic assessment suffers from substantial intra- and interobserver variation, up to 75 %, thereby limiting the reliability of individual assessments. Our aim was to develop an artificial intelligence (AI) model capable of distinguishing active from healed mucosa as well as to differentiate different levels of endoscopic disease activity. Methods 1484 unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independent of each other according to the Mayo endoscopic subscore (MES). In case of disagreement, a third expert classified the images. Different convolutional neural network architectures were implied in the development of the AI model. Five-fold cross-validation was employed to select the best model. Unseen test data were used for evaluation. The final model was evaluated on its performance for distinguishing MES 0 from 1–3, MES 0–1 (i.e. mucosal healing) from 2–3, and distinguish between all MES. The accuracy, sensitivity, specificity, positive and negative predictive value, and Cohen’s Kappa were used to evaluate the final models. Results Our final model achieved at the most difficult task (distinguishing between all 4 categories of MES) a mean accuracy of 0.82, mean AUC of 0.99, test accuracy of 0.84, a sensitivity of 0.88, and a specificity of 0.81 and a weighted Cohens Kappa of 0.83 (p<0.001 compared to the experts). The results from the other tasks are shown in table 1. Conclusion We propose a new standardised way of evaluating endoscopic images from UC patients for both clinical and academic purposes. The proposed AI model demonstrated a very good capability of distinguishing between all 4 MES levels of activity. This will optimize and unify the evaluation of the disease severity measured by the Mayo endoscopic subscore across all centres and hospitals no matter the level of medical expertise.

Crohn's disease (CD) and ulcerative colitis (UC) carries a high burden on healthcare resources. To date, no study has assessed the combined direct and indirect cost of inflammatory bowel disease (IBD) in a population-based setting. Our aim was to assess this in a population-based inception cohort with 10 years of follow-up. All incident patients diagnosed with CD or UC between 2003 and 2004 in a well-defined Copenhagen area, were followed prospectively until 2015. Information regarding direct and indirect costs was retrieved from the Danish national registries. Data were compared with a control population matched by age, sex and municipality with a ratio of 1:20 (10259). Using multiple linear regression models, associations between the total cost and multiple variables were assessed. A total of 513 (CD: 213 [42%], UC: 300 [58%]) IBD patients were included. No significant differences were found in indirect costs between CD, UC, and the control population regarding paid sick leave, unemployment benefits or loss of tax income. Costs for CD patients were significantly higher than UC regarding all direct expenditures (except for 5-ASA), but no differences were found in diagnostic expenses. The expenses for biologics were, respectively, €1.6 and 0.3 million for CD and UC. The total costs accounted for €42.6€ million. Figure 1 illustrates the distribution of all expenses; Figure 2 illustrates the total costs per patient each year. Subgroup analyses only revealed significant increased direct expenses in patients with extensive colitis (Proctitis: €2273 [1341–4092], left-sided: €3606 [2354–5311], extensive: €4093 [2313–6057], p < 0.001). Using multi-variable linear regression, no variables were significantly associated with increased total costs in CD or in UC patients. Abstract OP82 – Figure 1. Distribution of costs per year in patients with inflammatory bowel disease. Conventional medicine: 5-aminosalicylic acid, topical steroids, corticosteroids and immunosuppressants. Abstract OP82 – Figure 2. The average total cost per Crohn's disease and ulcerative colitis patient; including paid sick-leave, social benefits, lost tax income, diagnostic procedures, surgery, hospitalisation, and medication. In this prospective population-based cohort, direct costs for IBD remain high. However, indirect costs (sick leave, unemployment and loss of tax-income etc.) did not surpass the control population. Total costs were mainly driven by hospitalisation, but over time indirect costs accounted for a higher percentage; though also decreasing over years.

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

Patients with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are at risk of developing metabolic bone disease. No general agreement regarding osteoporosis screening by Dual-energy X-ray absorptiometry (DXA) in IBD patients exists. The aims were to investigate the screening strategy, incidence and risk factors of osteoporosis in a well-defined prospective population-based inception cohort. Between 2003 and 2004 all incident patients diagnosed with CD and UC in a clearly defined Copenhagen area were included and followed until 2015. Data regarding hospitalisation, diagnosis and treatment were collected from patient files and national registries. Data were compared with a control population (1:20). Poisson’s regression model was performed for osteoporosis and a combined variable of osteoporosis and osteopenia with several covariates. A total of 513 patients with IBD were included (213 CD, 300 UC). Overall, 297 (58%, CD: 144 [68%], UC: 153 [51%]) patients received ≥2 courses of steroids within a year, resulting in 624 patient-years where 2 or more courses of steroids where given within a year. Of those, only 65 (10.4%) cases of patient-years were followed by DXA within the same or next calendar year. Overall, 50 (9.7%, Table 1) IBD patients (CD: 21 [9.9%], UC: 29 [9.7%]) and 562 (5.5%, p < 0.001) controls were diagnosed with osteoporosis during follow-up (OR: CD: 1.9 [1.2–3.0], UC: 1.8 [1.2–2.7]). Age at diagnosis (IRR, CD: 1.05 [1.02–1.07], UC: 1.06 [1.04–1.10]) was significantly associated with the risk of osteoporosis. When assessing low energy fractures, 6 (2.8%) CD and 10 (3.3%) UC patients had at least one; independent of steroid treatment (p>0.05). No significant difference was found compared with the control population (238 [2.3%], p = 0.5). Assessment of BMD, T- and Z-score found on DXA showed no significant differences between UC and CD patients at any bone site, nor in subgroups of disease phenotypes. Table 1. Prevalence of osteoporosis and the frequency of Dual-energy X-ray absorptiometry in patients with inflammatory bowel disease. *Compared with those who did not fulfil the criteria in each respective subgroup. Table 1. Prevalence of osteoporosis and the frequency of Dual-energy X-ray absorptiometry in patients with inflammatory bowel disease. *Compared with those who did not fulfil the criteria in each respective subgroup. In this population-based inception cohort with 10 years of follow-up, 10% of IBD patients were diagnosed with osteoporosis, bone mineral density among patients at risk of osteoporosis receiving steroid treatment was inadequately evaluated. Increased attention to IBD patient at risk of metabolic bone disease must be prioritised and guidelines on this matter are warranted.

The long-term disease course of Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), in the age of biologics has not been well described. We aimed to characterise the disease course after 10 years in CD and UC patients in a well-defined population based inception cohort. All patients (n = 513) diagnosed with CD, UC or IBD unclassified between January 1, 2003 and December 31, 2004 in a well-defined Copenhagen area were included. Clinical data regarding treatment and outcome were recorded and patient records linked with four national registries to ensure complete data capture and follow-up. Major surgery was defined as any colectomy or intestinal resection. Disease classification was made according to the Montreal Classification. Hospitalisation was defined as any hospitalisation 3 months after date of diagnosis. Treatment with immunomodulators and biologics prior to the surgery was included in a regression model. A total of 213 CD and 300 UC were followed for a mean of 9.24 years (sd: 2.68). In CD, during follow-up 75 (35%) patients underwent at least one major surgery, while 196 (92%) were hospitalised at least once. The median length of stay (LOS) was 3 days (IQR: 1–8) and the median number of hospitalisation was 7 (IQR: 4–13). In UC, 35 (12%) patients had a colectomy and 258 (86%) were hospitalised. The median LOS was 3 days (IQR: 1–8) and median number of hospitalisations was 5 (IQR: 3–8). Cumulative risk of major surgery and associated factors are show in Table 1 and Figures 1 and 2. In the age of biologics, the risk of resection and hospitalisation remains high for CD as well as for UC. The use of immunomodulators but not biologics was associated with a reduced risk of surgery in CD. Cox regression analysis: predictors for surgery and hospitalisation in Crohn’s disease and ulcerative colitis patients after 10 years of follow-up. Risk of first, second, and third major surgery in Crohn’s disease patients after 10 years of follow-up. Risk of major surgery in ulcerative colitis patients after 10 years of follow-up.

Perianal complications in patients with Crohn’s disease (CD) are common and associated with a relapsing–remitting course with a negative impact on the patients’ quality of life. Data on the long-term disease course in the era of biological therapy are limited. In this population-based cohort study we sought to investigate the occurrence, clinical risk factors and disease course of perianal CD in the era of biologic therapy. A total of 213 CD patients diagnosed between January 1, 2003–December 31, 2004 were included in a prospective population-based inception cohort. Clinical data were retrieved from medical records and data on surgery, cancer, and death were crosschecked with register data from national health administrative databases until December 2016 ensuring complete follow-up. Perianal CD was defined as the occurrence of a perianal fistula and/or abscess. Associations between primary endpoints (surgery and hospitalisation) and covariates were analysed by Cox regression analysis. A total of 48 (25%) patients developed perianal CD after ten years. Colonic disease location (HR 1.99, 95% confidence interval (CI) 1.01–3.92) and penetrating behaviour (HR 5.65, 95% CI 2.65–12.03) were identified as predictors of perianal CD. The cumulative risk of undergoing perianal surgery and abdominal surgery after 10 years was 67% and 51%, respectively. Patients with perianal CD had a significantly higher rate of intestinal resections (HR 3.92, 95% CI 1.86–8.67). During a follow-up of 10 years, patients with perianal CD were hospitalised for 77.5 (interquartile range (IQR) 39.5–153.5) days in median compared with 46 (IQR 25–84) days in patients without. Total days of hospitalisation was significantly higher for patients with perianal CD (HR 1.01, 95% CI 1.004–1.011). Characteristics of patients at baseline stratified by perianal disease. Cumulative risk of undergoing resection among patients with and without perianal CD The incidence of perianal CD seems to have decreased compared with studies in earlier eras, which may be caused by an increased usage of biologic agents. However, the rate of both perianal and abdominal surgery remains high. We found a higher risk of intestinal resection and hospitalisation in patients with perianal CD suggesting a more severe and protracted course. These findings underline the importance of early identification of patients at risk of developing perianal CD who might benefit from early introduction of aggressive therapy.

Background: Crohn's disease (CD) is a progressive disease that over time can lead to the development of complications such as strictures or internal penetrating disease that will ultimately lead to surgery. Only few population-based studies have investigated the risk factors for disease progression in CD including the effect of smoking. We therefore sought to identify the risk factors associated with complicated CD in a Danish population-based inception cohort from the biological era. Methods: All incident patients diagnosed with CD or UC in a well-defined Copenhagen area 1.1.2003–31.12.2004 were registered and followed prospectively until 31.12.2011. Clinical data including medical and surgical treatment and disease phenotype according to the Montreal classification were registered. Disease progression in CD was defined as the first occurrence of a bowel stricture (B2) or internal penetrating disease (B3), defined by endoscopy, cross-sectional imaging or surgery, or the need for non-perianal surgery. Possible associations between disease progression and multiple covariates (age, gender, disease location, type of medical treatment, diagnostic delay and smoking status) were analysed by Cox regression analyses using the proportional hazard assumption. Results: The cohort consisted of 213 incident CD patients that were followed prospectively. Of those, a total of 165 (77%) patients had non-penetrating, non-stricturing disease behaviour (B1) at diagnosis and were included in the analysis. Of those with B1, 44 (27%) patients experienced progression of disease during the seven year follow-up: 21 (48%) B2, 5 (11%) B3, and 18 (41%) had surgery. Patients with ileal disease location (L1 or L3) had increased risk of disease progression (HR =2.1 CI95%: 1.1–4.0) as was also seen in patients who did not receive medical treatment during follow-up compared to those who did (HR =9.0 CI95%: 3.3–25.0). Other covariates including active smoking at the time of diagnosis were not associated with the risk for a disease progression. Conclusions: In this population-based inception cohort of unselected CD patients one out of four patients with B1 behaviour at diagnosis experienced disease progression during follow-up. Clinical variables associated with the risk of progression were ileal disease location and not receiving medical treatment for CD. Smoking was not associated with the risk of disease progression in CD.

SummaryBackgroundThe Inflammatory Bowel Disease Disability Index (IBD‐DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC).AimTo assess the severity of disability and associated factors using the IBD‐DI, and review the validity of the IBD‐DI as a tool.MethodSystematic review of cross‐sectional studies. Patients included had UC or CD and were classified as active, in remission, or needing surgery, biological and/or steroid treatment. We included studies assessing disability using the IBD‐DI and that were captured by electronic and manual searches (January 2017). The possibility of bias was evaluated with the Newcastle‐Ottawa Scale.ResultsNine studies were included with 3167 patients. Comparatively, patients with active disease had higher disability rates than those in remission (SMD [CI95] = 1.49[1.11, 1.88], I2 = 94%, P<.01), while patients on biological treatment had lower disability rates than those receiving corticosteroid treatment (SMD [CI95] = −0.22[−0.36, −0.08], I2 = 0%, P<.01). Disease activity and unemployment were found to be associated factors. The IBD‐DI scored “good” for internal consistency, “fair” to “excellent” for intra‐rater reliability and “excellent” for inter‐rater reliability. Construct validity was “moderately strong” to “very strong” and structural validity was found to be mainly unidimensional. The IBD‐DI had excellent responsiveness, while its interpretability was only useful on a group level.ConclusionsThis systematic review and meta‐analysis found a significant association between disease activity, treatment received and disability; although significant heterogeneity was found. The IBD‐DI is reliable and valid, but further studies are needed to measure its interpretability.

Background: Disease extent classified in ulcerative colitis (UC) as E1 (proctitis), E2 (left-sided) or E3 (extensive) is one of the major factors determining disease prognosis over the long-term. UC is a progressive and dynamic disease. We investigated the risk of UC extension and subsequent risk of surgery in a Danish population-based cohort from the biological era. Methods: All incident patients diagnosed with UC in a well-defined Copenhagen area 1.1.2003–31.12.2004 were followed prospectively until 31.12.2011. Disease extension was defined in patients with limited UC at diagnosis (E1 or E2) as a progression from the initial extent defined by endoscopy or surgery. The risk of colectomy was assessed in all incident patients. Associations between progression or colectomy and multiple covariates (age, gender, initial disease extent, type of medical treatment, diagnostic delay and smoking status) were analysed by Cox regression analyses using the proportional hazard assumption. Results: Among a total of 300 incident UC patients 220 (73%) had E1 or E2 at diagnosis. Extent at diagnosis and during follow-up is shown in Table 1. During the follow-up period, 50 (23%) patients with E1/E2 progressed to E3, and 22 (10%) patients with E1 progressed to E2. Disease extent at diagnosis was the sole significant predictor of extension to E3 with a higher risk in E2 than in E1 patients (HR =2.2 CI95%: 1.2–4.2). No significant predictors were found for extension from E1 to E2. During follow-up, a total of 34 (11%) patients had a colectomy. Of patients with E1/E2 as initial extent a total of 18 (8%) patients had a colectomy. Analyses of risk factors associated with colectomy are shown in Table 2. Progression from E1/E2 to E3, female gender and past history of smoking were significant risk factors for colectomy. Table 1. Disease extent in UC at diagnosis and follow-up Table 2. Risk factors associated with colectomy in ulcerative colitis patients Conclusions: After seven years follow-up, one out of three patients with limited UC experienced disease extension. Only extent at diagnosis was a clinical predictor for disease extension. The risk of colectomy was increased in ex-smokers, and patients who progressed to extensive colitis. This highlights the need of preventing progression in patients with limited UC as well as to identify new histological or molecular markers that enable physicians to identify patients at risk for disease progression.

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

Epidemiology S317 rural patients (p < 0.001).This difference was consistent during the entire study period.About one third of patients had a family history of IBD.Conclusions: The incidence and prevalence of paediatric IBD in Manitoba is rising.The majority of our patients were residents of urban Manitoba confirming the important role of environmental etiologic factors.

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

OBJECTIVE:The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN:A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS:1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS:An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Background and AimsThe incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more “westernised” standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.MethodsThe EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.ResultsA total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01).ConclusionsIn this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.