Increased use of biologics in the era of TNF-α inhibitors did not reduce surgical rate but prolonged the time from diagnosis to first time intestinal resection among patients with Crohn's disease and ulcerative colitis - a Danish register-based study from 2003-2016.

BACKGROUND: During the last decade, a significant increase in the use of biologic medicine has occurred, accounting for the greatest healthcare expenditure, among inflammatory bowel disease (IBD) patients. The objective of this study was to analyse the prevalence of and time to first intestinal resection surgery in a Danish nationwide cohort of Crohn's disease (CD) and ulcerative colitis (UC) patients, stratified on biologic treatment status. METHODS: This retrospective population-based study included IBD patients diagnosed between 2003 and 2015 identified in the Danish National Patient Registry (NPR). The frequency of first-time surgery with intestinal resection and time to surgery was analysed among CD and UC patients between 2003 and 2016. RESULTS: A total of 2328 CD and 2128 UC patients underwent surgery between 2003 and 2016 (23% and 10% of all incident CD and UC patients, respectively). Up until 2008, the frequency of surgery gradually declined for both patient groups and an increase in the frequency of patients receiving biological treatment was observed. Subsequently, the frequency of surgery for both CD and UC patients remained stable despite a steady increase in biologic treatment use. CONCLUSIONS: The registered increase in the fraction of patients on biologic treatment (mostly TNF-α inhibitors) did not result in changes in the rates of major surgeries with intestinal resection in CD and UC patients.

Costs of electronic health vs. standard care management of inflammatory bowel disease across three years of follow-up-a Danish register-based study.

BACKGROUND: Costs of using eHealth in inflammatory bowel disease (IBD) management has only been assessed for short follow-up periods. The primary aim was to compare the direct costs of eHealth (cases) relative to standard care (matched controls) for IBD during three years of follow-up. METHODS: The study design was a retrospective, registry-based follow-up study of patients diagnosed with IBD two years prior, and three years subsequent, to their enrolment in eHealth. Cases were matched 1:4 with controls receiving standard care based on diagnosis, gender, biologics (yes/no) and age (+/- 5 years). RESULTS: We identified 116 cases (76 (66%) with ulcerative colitis (UC) and 40 (34%) with Crohn's disease (CD)) and matched them with 433 controls. IBD-related outpatient costs were only significantly higher for cases in the year of their inclusion in eHealth (€2,949 vs. €1,621 per patient, p =.01). Mean IBD-related admission costs tended to fall after enrolment in eHealth, with mean admission costs per patient at year 3 of follow-up of €74 for cases and €383 for controls (p = .02). Linear extrapolation of the reduction in costs beyond year 3 after enrolment in eHealth revealed that eHealth would be cost neutral or saving, relative to standard care, from year 4. CONCLUSION: IBD-related outpatient costs in both groups were similar and only significantly higher for cases in the year of their enrolment in eHealth, with admission costs typically falling after a patient's inclusion in eHealth. Estimation revealed eHealth to be cost neutral or saving from year 4.

Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases.

BACKGROUND: Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE: To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS: A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS: The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION: Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

E-Health and remote management of patients with inflammatory bowel disease: lessons from Denmark in a time of need.

In Denmark, remote monitoring and management of inflammatory bowel disease (IBD) started two decades ago with the web application Constant Care. The disease monitoring in Constant Care consists of simple disease activity questionnaires and home measurement of faecal calprotectin, a stool biomarker for inflammation. It has now been implemented in clinical practice at North Zealand University Hospital in Denmark. Digital health care solutions facilitate remote contact between patients and healthcare providers and have been shown to reduce time to remission, outpatient visits and hospital admissions, and increase adherence to medical therapy, quality of life and disease and treatment knowledge. In Australia, E-Health is an area of increasing interest, particularly given the significant distances travelled by rural patients to access specialist care. There are several foreseeable benefits to incorporating E-Health/remote monitoring into Australian IBD management, including reduced burdens of time and cost on rural patients, and more efficient management of well outpatients, thereby increasing clinic availability for acutely unwell patients. The significant portion of IBD patients managed in private practice in Australia, and the infrastructure within private practice that is well suited to implementation of E-Health makes Australia a viable setting for an E-Health IBD management model like Denmark's Constant Care model. One pilot study is currently underway investigating the feasibility of rapid and remote IBD monitoring and E-Health in an Australian IBD population. The current COVID-19 pandemic has further illustrated the importance of telehealth as a means of maintaining health services to patients in geographic, or social, isolation.

The cost burden of Crohn's disease and ulcerative colitis depending on biologic treatment status - a Danish register-based study.

BACKGROUND: Patients diagnosed with inflammatory bowel disease may be treated with biologics, depending on several medical and non-medical factors. This study investigated healthcare costs and production values of patients treated with biologics. METHODS: This national register study included patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between 2003 and 2015, identified in the Danish National Patient Register (DNPR). Average annual healthcare costs and production values were compared for patients receiving biologic treatment or not, and for patients initiating biologic treatment within a year after diagnosis or at a later stage. Cost estimates and production values were based on charges, fees and average gross wages. RESULTS: Twenty-six point one percent CD patients and ten point seven percent of UC patients were treated with biologics at some point in the study period. Of these, 46.4 and 45.5 % of patients initiated biologic treatment within the first year after diagnosis. CD and UC patients treated with biologics had higher average annual healthcare costs after diagnosis compared to patients not treated with biologics. CD patients receiving biologics early had lower production values both ten years before and eight years after treatment initiation, compared to patients receiving treatment later. UC patients receiving biologics early had lower average annual production values the first year after treatment initiation compared to UC patients receiving treatment later. CONCLUSIONS: CD and UC patients receiving biologic treatment had higher average annual healthcare costs and lower average annual production values, compared to patients not receiving biologic treatment. The main healthcare costs drivers were outpatient visit costs and admission costs.

Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial.

BACKGROUND: The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. OBJECTIVE: The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients' microbiota. METHODS: Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). RESULTS: A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was -126.50 (IQR -196.75 to -76.75) and for VSL#3 it was -130.00 (IQR -211.00 to -70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients' microbiota. CONCLUSIONS: The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622.

Treatment patterns for biologics in ulcerative colitis and Crohn's disease: a Danish Nationwide Register Study from 2003 to 2015.

Background: The choice of treatment for Crohn's disease (CD) and ulcerative colitis (UC) depends among other factors, disease severity. Patients with moderate-to-severe disease should be prescribed biologic response modifiers (biologics), according to guidelines. This study aims to explore the treatment patterns of patients diagnosed with CD and UC between 2003 and 2015 that were treated with biologics in Denmark between the years 2003 and 2016.Methods: This national register study included patients diagnosed between 2003 and 2015, identified in the Danish National Patient Registry. Biologic therapies available during the study period were infliximab, adalimumab, vedolizumab and golimumab. The share of patients initiating and receiving biologic treatment in each year was estimated. Additionally, the time from IBD diagnosis to first biologic treatment and time between treatments was calculated.Results: Among 10,302 CD patients and 22,144 UC patients, 28.5% of CD patients and 11.3% of UC patients received treatment with biologics during the study period, with an increasing trend in the number of patients initiating treatment with biologics each year. About 46% of CD patients and 45% of UC patients received their first biologic treatment within the first year after IBD diagnosis. About 57-68% of CD and UC patients received treatment with their second line biologic within 2 months of the last treatment of their first line.Conclusions: The number of patients initiating biologic treatments after diagnosis increased throughout the study period. Most patients diagnosed with CD and UC are receiving biologic treatments relatively soon after their diagnosis.

Societal costs attributable to Crohn's disease and ulcerative colitis within the first 5 years after diagnosis: a Danish nationwide cost-of-illness study 2002-2016.

Objective: There is little information on cost-of-illness among patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) in Denmark. The objective of this study was to estimate the average 5-year societal costs attributable to CD or UC patients in Denmark with incidence in 2003-2015, including costs related to health care, prescription medicine, home care and production loss.Materials and methods: A national register-based, cost-of-illness study was conducted using an incidence-based approach to estimate societal costs. Incident patients with CD or UC were identified in the National Patient Registry and matched with a non-IBD control from the general population on age and sex. Attributable costs were estimated applying a difference-in-difference approach, where the total costs among individuals in the control group were subtracted from the total costs among patients.Results: CD and UC incidence fluctuated but was approximately 14 and 31 per 100,000 person years, respectively. The average attributable costs were highest the first year after diagnosis, with costs equalling €12,919 per CD patient and €6,501 per UC patient. Hospital admission accounted for 36% in the CD population and 31% in the UC population, the first year after diagnosis. Production loss exceeded all other costs the third-year after diagnosis (CD population: 52%; UC population: 83%).Conclusions: We found that the societal costs attributable to incident CD and UC patients are substantial compared with the general population, primarily consisting of hospital admission costs and production loss. Appropriate treatment at the right time may be beneficial from a societal perspective.

eHealth: Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis.

BACKGROUND/AIM: Microbial dysbiosis in inflammatory bowel disease (IBD) is poorly understood. Faecal samples collected for the purposes of microbiota analysis are not yet a part of everyday clinical practice. To explore associations between faecal microbiota and disease activity measures in adult IBD patients, for the purpose of possibly integrating microbiota measures in an existing IBD eHealth application for disease-monitoring. METHODS: We collected faecal samples from adult IBD patients for one year while they were home-monitoring for disease activity, using faecal calprotectin (FC) and the Simple Clinical Colitis Activity Index (SCCAI). Faecal samples were analysed in two different ways: commercially available test consisting of 54 pre-determined bacterial markers (DNA test) and 16S rRNA gene sequencing (16S-seq). Univariable linear mixed effect models were fitted to predict disease scores using normalised relative abundances as fixed effects. RESULTS: Seventy-eight IBD patients provided a total of 288 faecal samples for microbiota analysis. Two hundred and thirty-four of the samples were from patients with ulcerative colitis (UC). Peptostreptococcus anaerobius was found to correlate significantly with increasing FC, while an additional 24 genera were found to be associated with FC and/or SCCAI (16S-seq). Bacterial markers (DNA test) for Proteobacteria, Shigella spp. and Escherichia spp., were significantly correlated with increasing FC measures, while another 14 markers were found to be associated with FC and/or SCCAI. CONCLUSIONS: In patients with UC, results of both methods are associated with disease activity, correlating significantly with Peptostretococcus anaerobius (16S-seq) and with Proteobacteria, Shigella spp. and Escherichia spp. (DNA test).

Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5). CONCLUSION: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: An Epi-IBD study.

BACKGROUND AND AIM: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. METHODS: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis.

BACKGROUND: Mucosal healing is proposed as treat-to-target in ulcerative colitis (UC), even though the definition of mucosal healing remains contested as it has been suggested to be assessed by either endoscopy, histology or both. However, all definitions require an endoscopic evaluation of the mucosa. As endoscopies are invasive and uncomfortable to the patient we aimed to calibrate noninvasive predictors of mucosal inflammatory status defined by both endoscopy and histology. METHODS: UC patients (n = 106) undergoing a sigmoid-/colonoscopy were prospectively included. Feces (fecal calprotectin, FC), blood samples (hemoglobin, C-reactive protein, orosomucoid, erythrocyte sedimentation rate, albumin) and symptom scores (Simple Clinical Colitis Activity Index, SSCAI) were collected and analyzed. The colonic mucosa was assessed by the Mayo endoscopic sub score and biopsies were obtained for a histologic grading by Geboes score. Predictive cutoff values were analyzed by receiver operating characteristics (ROC). A combined endoscopic and histologic assessment defined deep remission (Mayo =0 and Geboes ≤1) and activity (Mayo ≥2 and Geboes >3). RESULTS: Only FC showed a significant ROC curve (p < .05). We suggest FC (mg/kg) cutoffs for detection of following: Deep remission: FC ≤25; Indeterminate: FC 25-230 - an endoscopy is recommended if a comprehensive status of both endoscopic and histologic assessed activity is needed; Active disease: FC >230. The complete ROC data is presented, enabling extraction of an FC cutoff value's sensitivity and specificity. CONCLUSIONS: FC predicts endoscopic and histologic assessed deep remission and inflammatory activity of colon mucosa. Neither the markers in blood nor the SCCAI performed significant ROC results.

Using eHealth strategies in delivering dietary and other therapies in patients with irritable bowel syndrome and inflammatory bowel disease.

Health-care systems around the world are facing increasing costs. Non-adherent, chronically ill patients are one such expense incurred by health-care providers. Web-based home-monitoring of patients-or eHealth-has been shown to increase adherence to medical therapy, facilitate contact between patients and health-care professionals, and reduce time to remission for patients with inflammatory bowel disease (IBD). Web-based treatment is a supportive tool for the health-care provider in an out-patient clinic. eHealth web-programs, such as the Constant Care application, visualize disease activity in a traffic light system and empower patients to screen for disease activity, enabling them to respond appropriately to their symptoms. The eHealth screening procedure for monitoring both pediatric and adult IBD patients is based on a self-obtained symptom score, together with a fecal biomarker for inflammation (fecal calprotectin) that the patients can measure independently using their smart phone, providing both patient and physician with an immediate disease status that they can react to instantaneously. Likewise, web applications for IBD patients, web applications for irritable bowel syndrome (IBS) patients and also IBD patients with co-existing IBS, have proven valuable for monitoring and treating IBS symptoms with a diet low in fermentable oligo-, di-, monosaccharides and polyols (low-FODMAP diet). With careful disease monitoring via the web application and increased patient adherence, eHealth might be capable of improving the natural disease course of IBD and IBS.

F-calprotectin and Blood Markers Correlate to Quality of Life in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Our aim was to investigate predictors of health-related quality of life (HRQoL) with respect to changes in disease parameters over time in children with inflammatory bowel disease. METHODS: This was a prospective longitudinal study examining the association between HRQoL (IMPACT III) and symptom scores (Pediatric Crohn Disease Activity Index, abbreviated Pediatric Ulcerative Colitis Activity Index), fecal calprotectin measures and blood analyses (C-reactive protein, erythrocyte sedimentation rate, orosomucoid, albumin, hemoglobin, and vitamin-D) in a cohort of 10- to 17-year-old patients with inflammatory bowel disease. Data were collected prospectively at 3-month intervals during a 2-year period. Associations were analyzed using linear mixed-effect models. Patients were divided into 2 groups, which received nonbiological oral treatment or biological parenteral treatment. RESULTS: From 79 patients (39 Crohn disease/40 ulcerative colitis), representing a total of 43,132 days of observation, 572 IMPACT measurements were paired with variables. A decrease in the IMPACT III score was significantly associated with increased ulcerative colitis-symptom score in the biological group (P = 0.005), and a similar inverse tendency was found in the nonbiological group and for Crohn disease symptoms in both groups. We found in both treatment groups overall a significant (P < 0.05) inverse association between the IMPACT III and the levels of fecal calprotectin, erythrocyte sedimentation rate, and orosomucoid, whereas albumin, hemoglobin, and vitamin-D were directly significantly associated. CONCLUSIONS: The IMPACT score, already known to correlate with disease activity, has now been shown to be associated with disease markers in feces and blood. This emphasizes that objective markers of disease activity indirectly can predict the patient's HRQoL.

The complexity of evaluating and increasing adherence in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs), due to their chronic and progressive nature, require lifelong treatment to relief and/or prevent inflammation and symptoms, obtaining mucosal healing at best. Therefore, adherence to treatment is an essential topic to address when treating patients with IBD. Nonetheless, adherence remains a common and complex issue in IBD care. Patient characteristics such as young age, male sex and employment has previously been verified as possible predictors of non-adherence. Additionally, evaluating adherence in itself is a challenge since both accurate and easy-to-use screening tools as well as golden standards are lacking.

The epidemiology of inflammatory bowel disease.

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing disorders of unknown aetiology. The aim of this review is to present the latest epidemiology data on occurrence, disease course, risk for surgery, as well as mortality and cancer risks. MATERIAL AND METHODS: Gold standard epidemiology data on the disease course and prognosis of patients with inflammatory bowel disease (IBD) are based on unselected population-based cohort studies. RESULTS: The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has increased overall in Europe from 6.0 per 100,000 person-years in UC and 1.0 per 100,000 person-years in CD in 1962 to 9.8 per 100,000 person-years and 6.3 per 100,000 person-years in 2010, respectively. The highest incidence of IBD is found on the Faroe Islands. Overall, surgery rates have been declining over the last decades, partly due to aggressive medical therapy. Among IBD patients, mortality risk is increased by up to 50% in CD when compared to the background population, but this is not the case for UC. In CD, 25 - 50% deaths are disease-specific deaths, e.g. malnutrition, postoperative complications and intestinal cancer. In UC, disease-specific causes of deaths include colorectal cancer (CRC), and surgical and postoperative complications. The risk of CRC and small bowel cancer is increased two- to eightfold among IBD patients. Various subgroups carry increased risk of malignancy, e.g. those with persistent inflammation, long-standing disease, extensive disease, young age at diagnosis, family history of CRC and co-existing primary sclerosing cholangitis. The risk of extra-intestinal cancers, including lymphoproliferative disorders (LD) and intra- and extrahepatic cholangio carcinoma, is significantly higher among IBD patients. CONCLUSION: In recent years, self-management and patient empowerment, combined with evolving eHealth solutions, has utilized epidemiological knowledge on disease patterns and has been improving compliance and the timing of adjusting therapies, thus optimizing efficacy by individualizing medication in the community setting.

Plain magnetic resonance imaging as an alternative in evaluating inflammation and bowel damage in inflammatory bowel disease--a prospective comparison with conventional magnetic resonance follow-through.

OBJECTIVE: To compare prospectively the diagnostic accuracy of magnetic resonance imaging (MRI) without use of contrast medium orally or intravenously (plain MRI) with magnetic resonance follow-through (MRFT) in patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS: Plain MRI was carried out in addition to MRFT, to which the patients were referred. All patients underwent both examinations on the same day. For the evaluation, the bowel was divided into nine segments. Two radiologists, blinded to clinical findings, evaluated bowel wall thickness, diffusion weighted imaging (DWI), and other inflammatory changes in each bowel segments. Further, hyperenhancement of the bowel was also evaluated in MRFT. RESULTS: A total of 100 patients (40 males and 60 females; median age: 38.5; range: 19-90) were enrolled; 44 with Crohn's disease (CD), 25 with ulcerative colitis (UC), 24 with IBD unclassified (IBD-U), and 7 had other diagnosis. Sensitivity, specificity, and accuracy in CD ranged 50-86%, 93-94%, and 91-92% for wall thickening and 49-82%, 85-93%, and 84-89% for DWI, respectively. Sensitivity, specificity, and accuracy in UC range 0-40%, 87-100%, and 80-100% for wall thickening and 0-52%, 83-94% and 76-92% for DWI, respectively. The κ values for bowel wall thickening, DWI, and mural hyperenhancement were detected with fair agreement (κ = 0.26-0.39) at both MRI examinations, whereas only bowel wall thickening in MRFT were detected with moderate agreement (κ = 0.47) Conclusion. Plain MRI cannot currently replace MRFT in the workup of patients with IBD. Further research on plain MRI is needed to improve the protocol.

Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

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.

The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.

BACKGROUND & AIMS: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. METHODS: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. RESULTS: The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P = .011). CONCLUSIONS: Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.

Disease course and surgery rates in inflammatory bowel disease: a population-based, 7-year follow-up study in the era of immunomodulating therapy.

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