Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort.

BACKGROUND: The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). AIMS: To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. METHODS: The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. RESULTS: We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. CONCLUSION: In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.

Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease.

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.

Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).

INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.

Frailty risk and treatment strategy in elderly-onset inflammatory bowel disease. A Norwegian nationwide population-based registry study.

BACKGROUND/AIMS: To determine real-world medical and surgical treatment patterns in elderly-onset inflammatory bowel disease in a nationwide cohort, and to investigate associations between frailty and treatment choices. METHODS: Norwegian health registries were used to identify adult-onset (born 1950-1989) and elderly-onset (born 1910-1949) patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed 2010-2017 (n = 13,006). Patients were classified as no, low and intermediate/high frailty risk after the Hospital Frailty Risk Score. Outcomes included use of medical and surgical treatment. RESULTS: Within five years, elderly-onset patients received less biologics (13% [CD], 7% [UC]) and immunomodulators (24% [CD], 11% [UC]), and major surgery was more frequent (22% [CD], 9% [UC]) than in adult-onset. Respective log rank tests were significant (p < 0.01). Compared to no frailty risk groups, elderly-onset UC with intermediate/high frailty risk had lower probability of starting biologics (4% versus 9%), immunomodulators (7% versus 13%) and 5-aminosalisylic acids (66% versus 84%), and elderly-onset CD with intermediate/high frailty risk had higher probability of starting prednisolone (67% versus 49%). Respective log rank tests were significant (p < 0.05). CONCLUSIONS: Elderly-onset patients received less biologics and immunomodulators and a larger proportion underwent major surgery. Frailty risk in elderly-onset patients was associated with increased use of prednisolone, and less use of 5-aminosalisylic acids, immunomodulators and biologics.

Dietary intake and nutritional status in patients with newly diagnosed inflammatory bowel disease: insights from the IBSEN III study.

BACKGROUND: Dietary recommendations in inflammatory bowel disease (IBD) are inconclusive, and patients may follow restrictive diets with increased risk of malnutrition. The aim of this study was to compare dietary intakes and nutritional status in men and women with newly diagnosed IBD with a general population sample, and to investigate whether intakes were in line with the Nordic Nutrition Recommendations. METHODS: This was a cross-sectional study including adults≥ 40 years with IBD from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III cohort study. A validated food frequency questionnaire (FFQ) was used in dietary data collection, and a sample from the seventh survey of the Tromsø Study was included as a comparison group. RESULTS: A total of 227 men and women with IBD were included. IBD patients had higher intake of grain products, sweetened beverages, energy, fat and polyunsaturated fat (PUFA), but lower intake of dairy products, alcohol and iodine compared to adults from the comparison sample (p < 0.01). Intakes of saturated fat and carbohydrates in both genders, and vitamin D in women were not within recommended levels. Anemia and hypoalbuminemia were more prevalent in IBD patients than in the comparison sample. CONCLUSIONS: Dietary intakes in newly diagnosed IBD patients were mostly in line with Nordic Nutrition Recommendations. Higher proportion of IBD patients exceeded recommended allowances of fat and added sugar than the comparison sample. Insufficient micronutrient intake, anemia and hypoalbuminemia are present challenges in IBD patients that require monitoring.

Self-prescribed dietary restrictions in patients with inflammatory bowel disease (IBD) due to inconclusive dietary guidance may influence their risk of malnutrition. Comprehensive assessment of both dietary intake and nutritional status as early as time of diagnosis may help identify challenges in this patient group and implement appropriate interventions.

The impact of proton pump inhibitors on the course of ulcerative colitis: a cohort study of over 10,000 newly diagnosed patients in Norway.

BACKGROUND AND AIMS: Proton pump inhibitors (PPI) affect the gastrointestinal microbiota, which is thought to play a role in the pathogenesis of ulcerative colitis (UC). Previous studies suggest an association between PPI use and risk of incident UC as well as disease course. The aim of the study was to examine if PPI exposure is associated with disease course in UC patients. METHODS: A national cohort consisting of all newly diagnosed UC patients from 2010 to 2020 was defined combining data from Norwegian registries. PPI exposure was included as a time dependent variable with a 30 day time lag from starting the drug. Outcomes were starting advanced therapies including anti-TNF, systemic glucocorticoids, any additional systemic anti-inflammatory medication and undergoing colectomy during follow-up. Time-dependent Cox regressions included the variables PPI use, first systemic glucocorticoid prescription, first UC hospitalization, age-groups and sex. RESULTS: The study cohort consisted of 10,149 patients with median age 40 years (IQR 27-56) and 56% males. PPI use independently increased the risk of starting advanced therapies (HR 1.54, 95% CI 1.36-1.73, p < 0.005), starting systemic glucocorticoids (HR 1.20, 95% CI 1.07-1.34, p < 0.005), starting any additional anti-inflammatory treatment (HR 1.18, 95%CI 1.05-1.32, p < 0.01) and undergoing colectomy (HR 1.52, 95%CI 1.17-1.98, p < 0.005). CONCLUSIONS: PPI use was associated with unfavorable outcomes including advanced therapy initiation, additional anti-inflammatory medications and undergoing colectomy. Although further studies are needed, the evidence suggests that PPIs could affect the course of UC and should be used cautiously in UC patients.

Symptoms and symptom clusters in patients newly diagnosed with inflammatory bowel disease: results from the IBSEN III Study.

BACKGROUND: Patients with inflammatory bowel disease report multiple symptoms, but the relationships among co-occurring symptoms are poorly understood. This study aimed to examine the prevalence of symptoms and explore symptom clusters and possible associations between symptom clusters and socio-demographic and clinical variables in patients newly diagnosed with inflammatory bowel disease. METHODS: The IBSEN III study is a prospective population-based inception cohort of patients with inflammatory bowel disease. This study used patient data from the three largest hospitals in the study catchment area. The Memorial Symptom Assessment Scale was used to assess the prevalence of symptoms. Symptom clusters were identified using principal component analysis. Possible associations between socio-demographic and clinical variables and symptom cluster membership were estimated using regression analysis. RESULTS: Of the 573 patients (age, ≥18 years) diagnosed with inflammatory bowel disease, 350 (61.1%) completed the questionnaire (responders). Eleven symptoms were reported by >50% of the responders. The three most prevalent symptoms were bloating (84%), drowsiness (81%), and lack of energy (81%). Three symptom clusters were identified: psychological (56% of the patients), impaired energy (28%), and physical (16%) clusters. Multinomial regression analysis revealed that vitamin D deficiency was significantly associated with the impaired energy cluster (odds ratio=2.49, 95% confidence interval [1.00-6.2], p=0.05). CONCLUSIONS: We found high symptom prevalence in patients newly diagnosed with inflammatory bowel disease. Three distinct symptom clusters were identified, and the psychological cluster includes >50% of the patients. Vitamin D deficiency is the only factor associated with cluster membership, namely the impaired energy cluster.

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation.

BACKGROUND AND AIMS: We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). METHODS: We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. RESULTS: In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. CONCLUSIONS: Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. IMPACT AND IMPLICATIONS: We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.

Fatigue in Patients with Newly Diagnosed Inflammatory Bowel Disease: Results from a Prospective Inception Cohort, the IBSEN III Study.

BACKGROUND AND AIMS: Although fatigue is common in inflammatory bowel disease [IBD], its pathogenesis remains unclear. This study aimed to determine the prevalence of fatigue and its associated factors in a cohort of patients newly diagnosed with IBD. METHODS: Patients ≥18 years old were recruited from the Inflammatory Bowel Disease South-Eastern Norway [IBSEN III] study, a population-based, observational inception cohort. Fatigue was assessed using the Fatigue Questionnaire and compared with data from a Norwegian general population. Univariate and multivariate linear and logistic regression analyses were performed to evaluate the associations of total fatigue [TF; continuous score] and substantial fatigue [SF; dichotomized score ≥4] with sociodemographic, clinical, endoscopic, laboratory, and other relevant patient data. RESULTS: In total, 983/1509 [65.1%] patients with complete fatigue data were included (ulcerative colitis [UC], 68.2%; Crohn's disease [CD], 31.8%). The prevalence of SF was higher in CD [69.6%] compared with UC [60.2%] [p < 0.01], and in both diagnoses when compared to the general population [p < 0.001]. In multivariate analyses, depressive symptoms, pain intensity, and sleep disturbances were associated with increased TF for both diagnoses. In addition, increased clinical disease activity and Mayo endoscopic score were significantly associated with TF in UC, whereas all disease-related variables were insignificant in CD. Similar findings were observed for SF, except regarding the Mayo endoscopic score. CONCLUSIONS: SF affects approximately two-thirds of patients newly diagnosed with IBD. Fatigue was associated with depressive symptoms, sleep disturbances, and increased pain intensity in both diagnoses, while clinical and endoscopic activity were associated factors only in UC.

Health-related quality of life in patients with newly diagnosed inflammatory bowel disease: an observational prospective cohort study (IBSEN III).

PURPOSE: This unselected, population-based cohort study aimed to determine the level of health-related quality of life (HRQoL) in patients with Crohn's disease (CD) and ulcerative colitis (UC) at the time of diagnosis compared with a reference population and identify the demographic factors, psychosocial measures, and disease activity markers associated with HRQoL. METHODS: Adult patients newly diagnosed with CD or UC were prospectively enrolled. HRQoL was measured using the Short Form 36 (SF-36) and Norwegian Inflammatory Bowel Disease Questionnaires. Clinical significance was assessed using Cohen's d effect size and further compared with a Norwegian reference population. Associations between HRQoL and symptom scores, demographic factors, psychosocial measures, and disease activity markers were analyzed. RESULTS: Compared with the Norwegian reference population, patients with CD and UC reported significantly lower scores in all SF-36 dimensions, except for physical functioning. Cohen's d effect sizes for men and women in all SF-36 dimensions were at least moderate, except for bodily pain and emotional role for men with UC and physical functioning for both sexes and diagnoses. In the multivariate regression analysis, depression subscale scores ≥ 8 on the Hospital Anxiety and Depression Scale, substantial fatigue, and high symptom scores were associated with reduced HRQoL. CONCLUSION: Patients newly diagnosed with CD and UC reported statistically and clinically significantly lower scores in seven of the eight SF-36 dimensions than the reference population. Symptoms of depression, fatigue, and elevated symptom scores were associated with poorer HRQoL.

Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type.

OBJECTIVES: Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. MATERIALS AND METHODS: This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn's disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. RESULTS: In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. CONCLUSIONS: Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants.

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

Therapeutic management and outcomes in inflammatory bowel diseases, 2010 to 2017 in cohorts from Denmark, Sweden and Norway.

BACKGROUND: Despite the increasing use of biologics in patients with inflammatory bowel disease (IBD), real-world data about outcomes in the era of biologics remain inconclusive. AIMS: To investigate trends in surgeries, hospitalisations and medication use in patients with IBD in a multinational, population-based cohort METHODS: We included 42,894 patients with ulcerative colitis (UC) and 24,864 with Crohn's disease (CD) who were diagnosed between 2010 and 2017 in Denmark, Norway and Sweden. We extracted data about surgeries, hospitalisations and medications from national registries and compared across countries and diagnosis years. RESULTS: Between 2010 and 2017, 2-year surgery rates were 4-7% in UC and 10-15% in CD and were stable over time. Two-year hospitalisation rates increased in Denmark (UC: 20% to 35%; CD: 27% to 32%) but were stable in Norway and Sweden (fluctuating between 33% and 37% in UC, and 46% and 52% in CD). Two-year rates of biologic use increased in both UC (7% to 16% in Denmark, 8% to 18% in Norway) and CD (22% to 26% in Denmark; 21% to 35% in Norway). Two-year rates of immunomodulator use increased in Norway (from 14% to 23% in UC; 37% to 45% in CD) and Sweden (from 41% to 52% in CD), but were stable in Denmark (between 17% and 21% in UC; 39% to 46% in CD). CONCLUSION: Between 2010 and 2017, surgery rates among Scandinavian patients with IBD remained stable, with no clear changes in hospitalisation rates despite the increasing use of immunomodulators and biologics.

First-line biologic treatment of inflammatory bowel disease during the first 12 months after diagnosis from 2010 to 2016: a Norwegian nationwide registry study.

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

Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway.

BACKGROUND AND AIM: Modern treatment strategies for inflammatory bowel disease (IBD) are postulated to change the natural disease course. Inception cohort studies are the gold standard for investigating such changes. We have initiated a new population-based inception cohort study; Inflammatory bowel disease in South Eastern Norway III (IBSEN III). In this article, we describe the study protocol and baseline characteristics of the cohort. METHODS: IBSEN III is an ongoing, population-based observational inception cohort study with prospective follow-up. Adult and pediatric patients with suspected IBD in the South-Eastern Health Region of Norway (catchment area of 2.95 million inhabitants in 2017), during the 3-year period from 2017 to 2019, were eligible for inclusion. Comprehensive clinical, biochemical, endoscopic, demographic, and patient-reported data were collected at the time of diagnosis and throughout standardized follow-up. For a portion of the patients, extensive biological material was biobanked. RESULTS: The study included 2168 patients, of whom 1779 were diagnosed with IBD (Crohn's disease: 626, ulcerative colitis: 1082, IBD unclassified: 71). In 124 patients, there were subtle findings indicative of, but not diagnostic for, IBD. The remaining 265 patients were classified as symptomatic non-IBD controls. CONCLUSION: We have included patients in a comprehensive population-based IBD cohort from a catchment population of 2.95 million, and a unique biobank with materials from newly diagnosed and treatment-naïve IBD patients and symptomatic non-IBD controls. We believe this cohort will add important knowledge about IBD in the years to come.

Thiopurines: Use them or lose them? International survey on current and future use of thiopurines in inflammatory bowel disease.

BACKGROUND AND AIMS: The role of thiopurines in therapeutic algorithms of Crohn's disease (CD) and Ulcerative colitis (UC) is being questioned. This work aimed to investigate current practice and future perspectives of Inflammatory Bowel Disease (IBD) physicians regarding the efficacy, safety, and role of precision medicine with thiopurines in IBD. METHODS: A 29-questions web-based survey was developed and distributed to IBD physicians worldwide. RESULTS: We collected the complete answers of 408 physicians from 50 countries. Most participants were experienced physicians in IBD; 26.0% met our definition of "IBD expert". Four physicians reported to not use thiopurines in clinical practice. Most respondents used thiopurines in monotherapy and in combination therapy, both in CD and UC. Respondents tended to consider thiopurines as drugs with a good safety profile, with the agreement of 61.5% of the overall cohort. A minority of physicians (~6%) considered that thiopurines will not be used in the future in IBD patients, while 57.8% believed that these drugs will still be used, in mono and combination therapy. CONCLUSION: Despite the many emerging treatments in IBD, according to the beliefs of most physicians surveyed, thiopurines will still be an important part of the treatment algorithm of both CD and UC.

Incidence and Prevalence of Inflammatory Bowel Disease in Norway and the Impact of Different Case Definitions: A Nationwide Registry Study.

BACKGROUND: Countries have different diagnostic procedures and treatment regimens for inflammatory bowel disease (IBD) patients. In addition to differences in population characteristics, completeness of data and health registries, different follow-up time and case definitions can have a large impact on estimates of the incidence and prevalence of IBD. AIM: The aim of this study was to use hospital and prescription data to estimate incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC), using different case definitions. METHODS: This study used nationwide data from the Norwegian Patient Registry (2008 to 2017) and the Norwegian Prescription Database (2004 to April 2018). Incidence and prevalence were estimated using different case definitions of an IBD patient, varying the number of IBD-related hospital visits and IBD prescriptions required. The base case definition included patients with at least one IBD hospital visit and two IBD prescriptions or two IBD hospital visits. RESULTS: From 2010 to 2017, 16,758 incident IBD patients fulfilled our base case definition, with 6045 diagnosed with CD (36.1%) and 10,713 (63.9%) with UC. For CD, 47.2% of the patients were male while 53.8% of UC patients were male. The base case incidence varied between 14.1 and 16.0 per 100,000 person-years for CD and 24.7 and 28.4/100,000 person-years for UC patients in the years 2010-2017. When we required at least two IBD hospital visits, not utilizing the prescription data, the CD incidence was 22.3 per 100,000 person-years in 2010 and 13.9 per 100,000 person-years in 2017. For UC, the incidence was 47.4 and 20.6 per 100,000 person-years in 2010 and 2017. In 2017, the prevalence of CD was 0.27% (95% CI: 0.26-0.27) and 0.50% (95% CI: 0.490-0.502) for UC. CONCLUSION: According to our base case definition, the incidence of IBD in Norway was stable from 2010 to 2017. Both the incidence and prevalence of IBD in Norway is among the highest in the world. Moreover, the study also highlights the consequences of different case definitions.

Risk of colorectal cancer in a population-based study 20 years after diagnosis of ulcerative colitis: results from the IBSEN study.

Objective: The association between ulcerative colitis (UC) and colorectal cancer (CRC) is widely accepted, although attenuated risk has been reported in recent years. Colonoscopic surveillance is recommended with intervals based on established clinical risk factors. Nevertheless, a significant number of patients develop interval cancers, indicating the need of improved individualised assessment. In the present study, we evaluated clinical risk factors associated with CRC during a prescheduled follow-up 20 years after diagnosis, the IBSEN study. Design: A population-based inception cohort of patients diagnosed with inflammatory bowel disease from 1 January 1990 until 31 December 1993, prospectively followed at 1, 5, 10 and 20 years after diagnosis. A total of 517 patients with UC were included; 264 (51 %) men; median age at inclusion 37.4 years (4-88). Results: The overall incidence of CRC was 1.6% (8/517) at a 20-year follow-up. The total lifetime risk of CRC prior to or after UC diagnosis was 2.3%. (12/517). Patients older than 70 years at diagnosis had a 15-fold higher risk of CRC compared with those diagnosed when younger than 40 years, with HR 15.68 (95% CI: 1.31 to 187.92). Neither sex, first-degree relative with CRC, extent of colitis nor primary sclerosing cholangitis affected the risk of CRC. Conclusion: The risk of CRC in UC was low and comparable with the risk of CRC in the background population of Norway.

Serological antibodies and surgery in a population-based inception cohort of Crohn's disease patients - the IBSEN study.

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