Swiss Inflammatory Bowel Disease Cohort Research Articles

Predictors of Temporary and Permanent Work Disability in Patients With Inflammatory Bowel Disease

Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease

ObjectivesWhether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric...

Sa1230 Frequency and Type of Side Effects of Immunomodulating Medication in the Swiss Inflammatory Bowel Disease Cohort

Sa1230 Frequency and Type of Side Effects of Immunomodulating Medication in the Swiss Inflammatory Bowel Disease Cohort

Mo1720 Frequency and Chronology of Extraintestinal Manifestations in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND/AIM: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies onmonitoring for TB reactivation and/or infection in this risk group are lacking. METHODS: We retested consecutive patients with inflammatory bowel disease (IBD) under therapy with TNFi for a minimum of 5 months for LTB by interferon-γ release assay (IGRA) and tuberculin skin test (TST). From each subject a detailed patient history and concomitant therapy were captured. RESULTS: After a median of 34.9 weeks (20.7-177.7) IGRA was retested in 184/227 patients (81.1%; Crohn's disease n= 139, ulcerative colitis n=45) initially screened for LTB and subsequently treated with TNFi. Additionally TST was re-administered in 144/227 subjects (63.4%). The majority of patients was TNFi naive (147/227, 79.9%). In 32 subjects isoniazid was provided prior and concurrently to TNFi due to LTB. In this subgroup retesting for LTB resulted in a reversion to negative in 6/13 patients (46.2%) and in 3/24 patients (12.5%, P=0.08) with a positive IGRA and positive TST at baseline, respectively. In patients without LTB at baseline no permanent IGRA conversion, but 6/144 (4.2%) TST conversions from negative to positive were observed. No single case of TB reactivation or infection was observed during the observation period. CONCLUSION: A conversion of IGRA during treatment with TNFi was not observed, but occurred for TST. IGRA frequently reverts to negative in patients with LTB after specific therapy and seems to be a sensitive method to monitor patients for LTB under treatment with TNFi.

Mo1037 Is There a Relationship Between Information Concerns of Patients and Adherence to Therapy? Findings From the Swiss Inflammatory Bowel Disease Cohort Study

Mo1037 Is There a Relationship Between Information Concerns of Patients and Adherence to Therapy? Findings From the Swiss Inflammatory Bowel Disease Cohort Study

Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity

Background & aimsTriggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses. We have previously demonstrated a substantial increase in TREM-1-expressing macrophages in the inflamed intestinal mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether serum sTREM-1 could be used as a surrogate marker of disease activity in patients with IBD. MethodsIntestinal biopsies and concurrently collected sera from patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1 expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were further determined in sera and colonic tissues collected at various time-points post disease induction in an experimental mouse model of colitis and correlated with disease activity. ResultsExpression of TREM-1 mRNA was upregulated in intestinal biopsies from patients with active disease but not in patients with quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal controls. No substantial differences in sTREM-1 expression levels were found in patients with active versus quiescent disease. In colitic mice, colonic TREM-1 mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA expression levels correlated with disease activity, augmented serum sTREM-1 in fact associated with a milder course of disease. ConclusionsAnalysis of sTREM-1 as a surrogate marker of disease activity in patients with IBD warrants caution.

P427 Information seeking activity and adherence to therapy: Findings from the Swiss Inflammatory Bowel Disease Cohort Study

P427 Information seeking activity and adherence to therapy: Findings from the Swiss Inflammatory Bowel Disease Cohort Study

Rising Incidence of Inflammatory Bowel Disease in Young Children

See “Epidemiology of Inflammatory Bowel Disease: Is There a Shift Towards Onset at a Younger Age?” by Braegger et al on page 141. Inflammatory bowel diseases (IBD) are ranked among the 5 most prevalent gastrointestinal diseases in the United States (1) and together they represent the most common chronic gastrointestinal disorder in children. About 25% of patients with IBD are diagnosed during childhood. The estimated annual disease-attributable direct cost of IBD is $6.3 billion, and the cost is significantly higher for children with IBD compared with adults (2). Recent epidemiological studies indicate a rising incidence of IBD in children, especially in those younger than 10 years old (3,4); these reports are of major concern. The Braegger et al (5) report in this issue addresses the important question of whether higher IBD prevalence in young children is a consequence of rising incidence or of a shift toward onset at a younger age. In this retrospective study, 1688 patients were enrolled from a Swiss IBD cohort and analyzed using a regression model. The study concludes that rising incidence of IBD in children was not because the age of onset has decreased. The authors further speculate that the increased prevalence of IBD in children is the result of a true rise in the incidence of childhood-onset IBD. Childhood-onset IBD has been proposed as a distinct disease form within a larger disease category because of the phenotypic variation and the differences in the natural history of IBD in young patients (6). There is no doubt that IBD is heritable: up to 30% of patients with IBD have a positive family history, and twin studies revealed >50% concordance rate among identical twins. With the advent of newer techniques such as genome-wide association studies, which uses high-density single-nucleotide polymorphism array technology, more than 50 disease-predisposing loci in IBD have been identified, confirming the richness of the heritability of IBD. These gene discoveries cannot explain the rising incidence of IBD in children, however, because the gene pool does not change rapidly in a few generations. This rapid rise in the incidence, if true, can only be attributed to either environmental factors such as infectious triggers and diet, or host factors such as immune inflammatory cells, intestinal epithelia, and microbial flora. In addition, gene–environment interactions may be important determinants of disease development, phenotype, and progression. Descriptive epidemiological studies such as the Braegger et al (5) study are limited in scope, but they do reveal some intriguing observations. We can only hope that many ongoing prospective epidemiological studies augmented with concurrent collections of genetic, serological, and microbiota data will yield much more needed information regarding disease pathogenesis, disease evolution, and risk stratification. There is a real optimism that the recent success in gene discovery efforts coupled with the ongoing follow-up studies on gene expression, functional studies of the genes, and gene–gene or gene–environment interactions will uncover new pathways and translate into improved clinical management. Perhaps the most intriguing piece that emerges from these genetic epidemiology investigations may be the ability to predict disease development in at-risk population, disease evolution, treatment responses, and finally disease-risk stratifications.

Epidemiology of Inflammatory Bowel Disease

Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease

The diagnosis of inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors. A total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was diagnostic delay. Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001). Seventy-five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months). Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient and doctor delays in this target population.

Infliximab for Crohnʼs disease in the Swiss IBD Cohort Study

Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.

Frequency and Risk Factors for Extraintestinal Manifestations in the Swiss Inflammatory Bowel Disease Cohort

Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients. IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed. A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients. EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management.

Appropriateness of therapy for fistulizing Crohn’s disease: findings from a national inflammatory bowel disease cohort

About 30-50% of patients with Crohn's disease (CD) develop fistulae, implying significant disease burden and complicated clinical management. To assess appropriate use of therapy for fistulizing CD patients enrolled in the Swiss Inflammatory Bowel Disease Cohort using criteria developed by the European Panel on the Appropriateness of Crohn's disease Therapy. Specific questionnaires were used to gather information on disease and its management. We assessed appropriateness of therapy at enrolment for adult CD patients with one or several fistulae. Two hundred and eighty-eight CD patients had fistulizing disease, of which 80% had complex fistulae and 32% currently had active draining fistulae. Mean age (s.d.) at diagnosis was 27 years (11), 51% males. Of the patients, 78% were judged as having globally an appropriate therapy, which was more often given for complex fistulae (87%) than for simple fistulae (67%). Antibiotics, azathioprine/MP, methotrexate and conservative surgery were almost always appropriate. Anti-tumor necrosis factor α was considered globally appropriate (91%), although most often with an uncertain indication. The 5ASA compounds, steroids and aggressive surgery were most often inappropriate (84%, 58% and 86% respectively). Formal appropriateness criteria for CD therapy were applied to a national cohort of IBD patients. For more than three-quarters of the patients with fistulizing CD, therapy was globally appropriate.

Prevalence of anaemia in inflammatory bowel disease in Switzerland: A cross-sectional study in patients from private practices and university hospitals

Background Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. Methods Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤ 120 g/L in women and ≤ 130 g/L in men. Results 125 patients from RC (66 with Crohn's disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P < 0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P = 0.032). Supplementation therapy (iron, vitamine B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. Conclusions Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy.

W1018 Relationship Between the Location of Colonic Diverticulosis and the Visceral Fat Accumulation. Crucial Role of the Visceral Fat Accumulation for the Formation of Left Sided Colonic Diverticulosis

Introduction Inflammatory bowel disease (IBD) is a chronic condition affecting relatively young patients. It is unclear how these patients search for information on their disease. The goal of this survey was therefore to consider patient input in order to develop a specific website by identifying relevant target information more precisely. Methods The Swiss Inflammatory Bowel Disease Cohort (SIBDC) started in Nov. 2006 and has enrolled nearly 1600 patients in university centers, regional hospitals and private practices. Two short questionnaires were sent to all the patients in the cohort. The first, a short one-page questionnaire, was used to identify current information resources used by patients to gather information about disease. The second was a narrative questionnaire, used to identify which kind of specific information patients were seeking. The questionnaire was divided into 4 parts, each focusing on a different phase of disease history: 1st symptoms, time of diagnosis, worsening of disease and disease remission. Results Questionnaires were sent to the 1566 IBD patients enrolled in the cohort from Nov. 2006 to Sep. 2009. 64 were excluded (wrong address). 681 patients (45%) replied. The characteristics of those who responded were quite similar to the whole cohort. Information sources consulted to gather information on their disease were: gastroenterologist (90%), internet (67%), family doctor (38%), books (30%), TV (17%) and patient associations (13%). 586 (86%) patients accessed the internet at home or at work, 60% having access on a daily basis. The information currently sought by patients on websites was advances in research (37%), therapies (especially adverse effects of therapy and alternative medicine) (25%) and daily disease management tips (15%). Patients sought information at the time of their initial symptoms, mainly through physicians or the internet; 48% were satisfied with what they found. 80% of patients sought information just after initial diagnosis, 74% during flares or complications and 65% in periods of remission. The main information topic consulted during relapses concerned therapies (41% of patients who are seeking information); during periods of disease remission it was mostly linked to advances in research (44%). Conclusion This survey performed in a large national IBD cohort reports for the first time on how patients look for information on their chronic disease. Gastroenterologists and the internet are the main sources of information. These results will facilitate the creation of an information website tailored to patients' needs.

S1037 Detection Bias Influences Increasing Rates of Microscopic Colitis: A Population Based Study

Background and Aim: Anemia is a common complication of inflammatory bowel disease (IBD) in both Crohn's disease (CD) and ulcerative colitis (UC). Studies on anemia in patients with IBD are usually conducted in tertiary referral centers. Unfortunately, data from private clinical practice is missing. The aim of the present study was to investigate the occurrence of anemia in IBD patients from University Hospitals and from private practices and to compare those results to healthy blood donor candidates. Methods: Data (such as age, gender, hemoglobine level, disease severity) was acquired prospectively from patients included in the Swiss IBD Cohort Study. The control population consisted of healthy first-time blood donor candidates at the blood transfusion center, Swiss Red Cross, Basel. IBD activity was measured in CD by the Crohn's disease activity index (CDAI) and in UC by the modified Truelove and Witts activity index (MTWAI). Anemia was defined as haemoglobin level ≤ 120 g/l in women and ≤ 130 g/l in men. Iron deficiency anemia was defined by a ferritin level 150, MTWAI >3) was defined as iron deficiency anemia in combination with anemia of chronic disease. Results: 125 patients from University Hospitals (66 CD and 59 UC) and 116 patients from private practices (71 CD and 45 UC) were included and compared to a control population (6074 blood donor candidates). In women from University Hospitals, anemia was significantly more frequent than in women from private practice and healthy female blood donors (30.4% vs. 11.9% vs 4.0%, p< 0.0001). In men anemia was less pronounced but reached statistical significance (27.8% vs. 14.3% vs. 2.8%, p< 0.001). CDAI was significantly higher in University Hospitals as compared to private practice (97.1± 72.4 vs. 64.7± 58.8, p=0.006) whereas the MTWAI was comparable (5.4 ± 4.5 vs. 3.9 ± 3.9, p=0.07). Anemia caused by iron deficiency was found in 60% of the IBD-patients from tertiary centers with anemia, but just in 18% of the IBD patients from private practice with anemia (p= 0.025). Supplementation therapy with iron/folic acid/vitamin B12 was applied more often in private practice than in University Hospitals (42% vs. 27%, p=0.01). Conclusions: Frequency of anemia in IBD patients is high in both tertiary referral centers and in private practice but is more pronounced in tertiary referral centers. The anemia is mainly caused by iron deficiency indicating that private practice gastroenterologists are more aware of potential iron deficiency and subsequent substitution therapy.

S1036 Anemia in Inflammatory Bowel Disease: Differences Between Private Practice and University Hospital: A Prospective Study

Background and Aim: Anemia is a common complication of inflammatory bowel disease (IBD) in both Crohn's disease (CD) and ulcerative colitis (UC). Studies on anemia in patients with IBD are usually conducted in tertiary referral centers. Unfortunately, data from private clinical practice is missing. The aim of the present study was to investigate the occurrence of anemia in IBD patients from University Hospitals and from private practices and to compare those results to healthy blood donor candidates. Methods: Data (such as age, gender, hemoglobine level, disease severity) was acquired prospectively from patients included in the Swiss IBD Cohort Study. The control population consisted of healthy first-time blood donor candidates at the blood transfusion center, Swiss Red Cross, Basel. IBD activity was measured in CD by the Crohn's disease activity index (CDAI) and in UC by the modified Truelove and Witts activity index (MTWAI). Anemia was defined as haemoglobin level ≤ 120 g/l in women and ≤ 130 g/l in men. Iron deficiency anemia was defined by a ferritin level 150, MTWAI >3) was defined as iron deficiency anemia in combination with anemia of chronic disease. Results: 125 patients from University Hospitals (66 CD and 59 UC) and 116 patients from private practices (71 CD and 45 UC) were included and compared to a control population (6074 blood donor candidates). In women from University Hospitals, anemia was significantly more frequent than in women from private practice and healthy female blood donors (30.4% vs. 11.9% vs 4.0%, p< 0.0001). In men anemia was less pronounced but reached statistical significance (27.8% vs. 14.3% vs. 2.8%, p< 0.001). CDAI was significantly higher in University Hospitals as compared to private practice (97.1± 72.4 vs. 64.7± 58.8, p=0.006) whereas the MTWAI was comparable (5.4 ± 4.5 vs. 3.9 ± 3.9, p=0.07). Anemia caused by iron deficiency was found in 60% of the IBD-patients from tertiary centers with anemia, but just in 18% of the IBD patients from private practice with anemia (p= 0.025). Supplementation therapy with iron/folic acid/vitamin B12 was applied more often in private practice than in University Hospitals (42% vs. 27%, p=0.01). Conclusions: Frequency of anemia in IBD patients is high in both tertiary referral centers and in private practice but is more pronounced in tertiary referral centers. The anemia is mainly caused by iron deficiency indicating that private practice gastroenterologists are more aware of potential iron deficiency and subsequent substitution therapy.