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Sandre Svatun Lirhus,1 Marte Lie Høivik,2,3 Bjørn Moum,2,3 Karoline Anisdahl,2,3 Hans Olav Melberg1 1Department of Health Management and Health Economics, University of Oslo, Oslo, Norway; 2Department of Gastroenterology, Oslo University Hospital, Oslo, Norway; 3Institute of Clinical Medicine, University of Oslo, Oslo, NorwayCorrespondence: Sandre Svatun LirhusDepartment of Health Management and Health Economics, University of Oslo, Forskningsveien 3A, Harald Schjelderups Hus, Oslo, 0373, NorwayTel +47 97 58 29 25Email s.s.lirhus@medisin.uio.noBackground: 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.Keywords: inflammatory bowel disease, incidence, prevalence, real-world data

Background and Aims: Fatigue is commonly observed in Crohn's disease (CD) and ulcerative colitis (UC), but its association to achieving remission is not clearly established. In this study we describe the odds for fatigue in patients with CD/UC one year after diagnosis based on different definitions of remission and identified factors associated with chronic fatigue (CF) among patients in endoscopic/radiological remission., Methods: Patients ≥18 years with CD/UC were recruited from the IBSEN III cohort. Using the Fatigue Questionnaire, and dichotomizing the score, CF was defined as the presence of substantial fatigue (SF) for ≥6 months. Remission was divided into symptomatic (CD: HBI score<5/UC: SCCAI score<3), biochemical (faecal calprotectin ≤250µg/g), endoscopic/radiological (CD: normal intestinal MRI/CT combined with normal endoscopy/UC: Mayo endoscopic score 0) and histological (normal mucosal biopsies). Both the likelihood of SF/CF, depending on the definition of remission, and associations between CF and selected factors for CD/UC in endoscopic/radiological remission, were evaluated using binary logistic regression analysis., Results: In total, 711/1416 patients were included. For both CD and UC, symptomatic remission significantly reduced the odds for SF and CF. Additionally, the odds for SF were significantly reduced for UC in biochemical remission. Among those in endoscopic/radiological remission (n=181), CF was independently associated with sleep disturbances (OR=10.40, 95%CI [3.28;32.99], p<0.001) and current treatment with infliximab (OR=4.31, 95%CI [1.15;16.17], p=0.03)., Conclusions: Stricter definitions of disease remission were not associated with a decreased likelihood of fatigue. For patients in endoscopic/radiological remission, CF was independently associated with sleep disturbances and current treatment with infliximab., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases 1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn's disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner's glands. Although previously linked to mucosal healing 4 , we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases., Competing Interests: Competing interests: S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. R.E. is an equity holder in EnsoCell. P.K. has consulted for AstraZeneca, UCB, Biomunex and Infinitopes. N.M.P reports consulting fees from Infinitopes. J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, Moderna and Grunenthal. A.S. is the recipient of research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Pfizer, Alimentiv, Boehringer Ingelheim and Agomab and has received consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Agomab, Goodgut and Orikine. R.E. and S.A.T are inventors on the patent GB2412853.0 filed in the UK, some components of which are related to this work. All other authors declare no competing interests., (© 2024. The Author(s).)

Extensive patient heterogeneity is a challenge in the management of inflammatory bowel disease (IBD). Sex and gender, as well as the interaction of sex and gender with other social identities, referred to as intersectionality, contribute to this heterogeneity and might affect IBD outcomes. An interdisciplinary team of clinicians, researchers, patients, and sex and gender experts reviewed current literature on the effect of sex and gender dimensions on IBD outcomes. The team also investigated the role that stakeholders have in advancing sex-based and gender-based IBD knowledge, as comprehensive studies are scarce. Acknowledging and integrating sex and gender into the organisation and content of research (eg, study design, participant recruitment, data analysis, data interpretation, data dissemination, and impact evaluation) could enhance the validity, relevance, and applicability of research. Such gendered innovation has potential for advancing personalised medicine and improving the quality of life for people with IBD., Competing Interests: Declaration of interests JH has served as a speaker or advisory board member for AbbVie, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Index Pharma, Janssen, Meda Pharmaceuticals, Medivir, Novartis, Pfizer, Prometheus Laboratories, Sandoz, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, and Union Chimique Belge, and has received grant support from Janssen, Merck Sharpe & Dohme, and Takeda. VA has served as an advisory board member for Merck Sharpe & Dohme. MDJ has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Tillotts Pharma, Takeda, Norgine, and Olympus. MR reports consulting fees from Janssen as part of a half-day advisory meeting concerning the use of a medication in clinical gastroenterology and payment from AbbVie as compensation for one lecture during Swedish Gastro Week on quality management within IBD; compensation for both was administrated as part of his job as a consultant of gastroenterology and hepatology. JDF reports support for attending meetings and travel from Tillotts and the Danish Society for Gastroenterology and Hepatology. MC has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Vifor Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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., Competing Interests: Conflict of interest K.A. reports consultant fees from Takeda outside the submitted work. S.S.L. reports grants and consultant fees from Takeda. A.W.M. reports grants from Takeda. B.M. reports consultant fees from Takeda, Janssen, AbbVie, Galapagos, Pfizer, Sandoz, Pharmacosmos as, Ferring as, Tillotts Pharma; speaker fees from Takeda, Janssen, Pfizer, AbbVie, Sandoz, Orion Pharma, Ferring as, Tillotts Pharma. H.O.M. reports grants and consultant fees from Takeda. M.L.H. reports speaker fees from Galapagos, Ferring, BMS, Janssen, AbbVie, Meda, Tillotts and Takeda; advisory boards for Takeda, Galapagos, BMS and AbbVie; investigator-initiated research grants from: Takeda, Pfizer, Tillotts and Ferring., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

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., (© 2024. The Author(s).)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment., Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models., Results: We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P  = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P  = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up., Conclusions: Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe., Competing Interests: T.H.W. and K.A. report consultant fees from Takeda outside the submitted work. A.W.M. reports research grant from Takeda. B.M. reports consultant fees from Takeda, Janssen, AbbVie, Pfizer; advisory board Takeda, Janssen, AbbVie, Pfizer, Sandoz, Pharma Cosmos; speaker fees from Takeda, Janssen, AbbVie, Sandoz, Orion Pharma. M.L.H. reports speaker fees from AbbVie, Meda, Tillotts, and Takeda; advisory board Takeda. M.H., L.B., N.B., and D.J.W. report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

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.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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 (Q 1; Q 3 ) 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.

Objective: Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM)., Methods: Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch. Primary outcome was proportion of patients on SC treatment after 26 weeks. Secondary outcomes included adverse events (AEs), clinical disease activity, biochemical markers, treatment interval, serum-VDZ (s-VDZ), preferred route of administration and health-related quality of life., Results: In total, 108 patients were switched. After 26 weeks, 100 patients (92.6%) were still on SC treatment and median s-VDZ was 47.6 mg/L (IQR 41.3 - 54.6). The most frequent AE was injection site reaction (ISR), reported by 20 patients (18.5%). There were no clinically significant changes in disease activity, biochemical markers and quality of life. The proportion of patients preferring SC administration increased from 28.0% before switch to 59.4% after 26 weeks ( p  < 0.001)., Conclusions: Nine out of ten patients still received SC treatment after 26 weeks. No change in disease activity occurred, and levels of serum VDZ increased. Although almost one fifth of patients experienced ISRs, a higher proportion favored SC administration at 26 weeks. This study demonstrates that SC maintenance treatment is a safe and feasible alternative to IV treatment.

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers., Competing Interests: Declaration of interests JB reports personal fees from AbbVie, Celgene, Pfizer, Samsung Bioepis, Pharmacosmos, Ferring, and Galapagos; grants and personal fees from Janssen, MSD, Takeda, Tillots Pharma, and Bristol Myers Squibb; and grants from Novo Nordisk. MZ has received support for attending a meeting from Takeda. PDC has received grants or contracts from Janssen, Takeda, Ferring, Shire, AbbVie, Celltrion, and Baxter. PDC has been a speaker, consultant, and advisory board member for AbbVie, Janssen, Takeda, Celltrion, Ferring, Shire, and Baxter; received support for travel or attending meetings or both from Ferring, Shire, Janssen, AbbVie, Takeda, Celltrion, and Baxter; and has been a member of the Australia and New Zealand IBD Research Consortium. SV has received research grants from Pfizer, Galapagos, AbbVie, Johnson & Johnson, and Takeda; consulting fees from AbbVie, AbolerIS Pharma, Agomab, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma, Zealand Pharma; speaker fees from Alimentiv, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, Pfizer, Takeda, and Tillots Pharma. CNB has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharma, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; is a consultant for Mylan Pharmaceuticals and Takeda; and educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. CNB is on the speaker's panel for AbbVie Canada, Janssen Canada, Medtronic Canada, and Takeda Canada; and has received research funding from AbbVie Canada and Pfizer Canada. GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Amgen, Sandoz, Pendopharm, and Takeda. He has received research support from Ferring. He shares ownership of a patent: treatment of inflammatory disorders, autoimmune disease, and pbc (WO2019046959A1. PCT/CA2018/051098) since Sept 7, 2018. DD has received lecture or consultancy fees from Takeda, Janssen, and Pfizer, and support for travel or attending meetings or both from Janssen and Takeda. MW has received grants or contracts from Mitsubishi Tanabe Pharma, Takeda, Zeria Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical, Kyorin Pharmaceutical, AbbVie, EA Pharma, Kissei Pharmaceutical, and Alfresa Pharma; consulting fees from AbbVie, EA Pharma, Eli Lilly Japan, Gilead Sciences, Nippon Boehringer Ingelheim, and Takeda Pharmaceutical; and honoraria from EA Pharma, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Zeria Pharmaceutical, Pfizer Japan, Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceutical, Celltrion Healthcare, JIMRO, Eli Lilly Japan, and Mochida Pharmaceutical. LT has received grants or contracts from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, and Amgen; consulting fees from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, Fresnius Kabi, and Viatris; and honoraria for lectures from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, and Organon. KP is an employee of Genentech–Roche and a shareholder of the Roche Group. KHK has served as speaker, consultant, and advisory member for or has received research funding from AbbVie, Amgen, Enorasis, Epsilon Health, Dr Falk Pharma, Faran Ferring, Genesis, Grifols, Janssen, Koper, MSD, Mylan, Shire, Takeda, and Vianex. MLH has received investigator-initiated research grants from Tillotts, Ferring, Takeda, and Pfizer; advisory board honoraria from Takeda and AbbVie; and speaking fees from Takeda, AbbVie, Tillotts, Ferring, Galapagos, Janssen, and MSD. ZK has served as speaker for AbbVie, Takeda, Janssen, Freseinus, and Oktal Pharma/Celltrion. MC has served as a speaker, as a consultant, or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Biogen, Gilead, and Eli Lilly. EVL has received grants or contracts from AbbVie, Bristol Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, and UCB; consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, Janssen, Iterative Scopes, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Takeda, and UCB; reports the following patents: USA 11 249 084 (issued), USA 10 041 948 (issued), and USA 17 668 915 (pending); has participated on a data safety monitoring board or advisory board for Eli Lilly and Morphic; owns stock in Exact Sciences; and is a board member of Crohn's & Colitis Foundation, Minnesota-Dakotas Chapter. PLL has been a speaker or advisory board member, or both, for AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genentech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Takeda, Tillots, and Viatris, and has received unrestricted research grants from AbbVie, Gilead, Takeda, and Pfizer. JPG has served as a speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers Squibb, Gilead/Galapagos, Eli Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma. WB has received research grants from Vifor Pharma and B Braun Medical; consulting fees from Takeda and B Braun Medical; speaker fees from Medtronic, Takeda, B Braun Medical, and Johnson & Johnson; and is a stock owner of Semiflex Company. RBG has received grants or contracts from AbbVie and Janssen; consulting fees from AbbVie; and honoraria for lectures from AbbVie and Cornerstone Health. MDK has received grants or contracts from Pfizer, Takeda, Janssen, AbbVie, Eli Lilly, Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, and Arenapharm; consulting fees from Takeda and Pfizer; speaker fees from AbbVie; has participated on data safety monitoring board or advisory board for Eli Lilly; and owns stock in Johnson & Johnson. MJP has received grants or contracts from Takeda, Janssen, Galapagos, Tramedico, MSD, Takeda, Janssen, and Bristol Myers Squibb; honoraria for lectures from Bristol Myers Squibb, Janssen, AbbVie, and Galapagos; consulting fees from Janssen and Gilead; and has a leadership or fiduciary role in the MyCoach foundation. JMA has served as speaker, consultant, and advisory member for AbbVie, Allergan, Anatara, Atmo Capsule, Bayer, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Ferring Fresenius Kabi, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Pfizer, Sandoz, Shire, Takeda, and Vifor; has participated on a data safety monitoring board or advisory board for Janssen; has received research grants from the Royal Adelaide Hospital research fund, The Hospital Research Fund 2020–22, and The Helmsley Trust 2020–23. SCN has received grants or contracts from AbbVie, Ferring, and Olympus and Janssen; consulting fees from AbbVie, Pfizer, Ferring, and Janssen; honoraria for lectures from AbbVie, Ferring, Janssen, Menarini, Takeda, Tillotts and Pfizer; has participated on a data safety monitoring board or advisory board for AbbVie, Pfizer, Ferring, and Janssen; is a shareholder of GeniBiome; and is a director of the Microbiota I-Center, Hong Kong. HOM has received research grants from Takeda and Biogen, consulting fees from Takeda, and speaking fees from Pfizer and Biogen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s).)

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., (© 2022 John Wiley & Sons Ltd.)

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., Competing Interests: Conflict of interest statement P.S. and M.L.H report no conflicts of interest. P.M. is a consultant for Abbvie, Ferring, Hospira, Janssen, MSD, Pfizer, Takeda. A.A. received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Gilead, Janssen, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sandoz and Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Ferring, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Samsung Bioepis, Takeda and Tigenix; and research grants from MSD, Pfizer and Takeda. A.D. has received research support or acted as a principal investigator for Abbvie, Dr. Falk Pharma, Celgene, Gilead, Janssen and Takeda; has acted as a consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Fresenius Kabi, Celltrion, Janssen, MSD, Pfizer, Roche, Takeda, Tillotts, Galapagos, Gilead, Pharmacosmos and Vifor; and has participated in speaker bureaus for AbbVie, Falk Foundation, Ferring, Janssen, Med Update, MSD, Pfizer, Roche, Takeda, Tillotts, and Vifor. M.B.A. has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. S.V. received consultant fees and unrestricted research grants from Abbott, Celtrion, Ferring, MSD, Pfizer, Sanofi-Aventis, Takeda, Tillots, UCB, Vifor and Falk Pharma. R.S.H. has received speaker fees from AbbVie, Janssen, Pfizer and Takeda. P.G.K has served as speaker and consultant for Abbvie, Janssen, Takeda, Pfizer, Novartis, and has received scientific grants from Takeda and Pfizer. L.P.-B. reports personal fees from Merck, Abbvie, Janssen, Ferring, Tillots, Celltrion, Takeda, Pfizer, Amgen, Biogen, Samsung Bioepis, Genentech, Vifor, Pharmacosmos, Biogaran, Boerhinger-Ingelheim, Lilly, Index Pharmaceuticals, Sandoz, Celgene, Alma, Sterna, Nestlé and Enterome. F.M. has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen., (Copyright © 2021. Published by Elsevier Ltd.)

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.

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.

Background & Aims: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD)., Methods: Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD without PSC, were subjected to metagenomic shotgun sequencing, generating 17 billion paired-end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses., Results: Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, Eubacterium spp and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched-chain amino acid synthesis (Q fdr < .05). Targeted metabolomics of plasma from an independent set of patients with PSC and controls found reduced concentrations of vitamin B6 and branched-chain amino acids in PSC (P < .0001), which strongly associated with reduced liver transplantation-free survival (log-rank P < .001). No taxonomic or functional differences were detected between patients with PSC with and without IBD., Conclusions: The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Our aim in this study was to analyze the importance of childbearing for risk of inflammatory bowel disease. Using data from the Norwegian Population Register and the Norwegian Patient Register, we fitted discrete-time hazard models for diagnosis of Crohn disease (CD) or ulcerative colitis (UC) among men and women aged 18-81 years in 2011-2016. Year and various sociodemographic factors were controlled for. The data included 4,304 CD cases and 8,866 UC cases. Women whose youngest child was ≤4 years of age had lower CD risk the following year than childless women (odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.62, 0.86). There was no such reduction in CD risk among fathers. Men whose youngest child was aged ≥20 years had higher risks of CD (OR = 1.22, 95% CI: 1.01, 1.49) and UC (OR = 1.15, 95% CI: 1.02, 1.30) than childless men. UC risk was also increased among men whose youngest child was aged ≤4 years (OR = 1.14, 95% CI: 1.02, 1.27). The short-term reduction in women's CD risk after a birth may reflect biological effects of pregnancy. Alternatively, it may reflect residual confounding or lifestyle effects of parenthood that are of special relevance for CD in women. In particular, differences in use of oral contraceptives (which it was not possible to control for) may have contributed to the observed pattern., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: Patients with inflammatory bowel disease (IBD) often suffer from musculoskeletal manifestations. Health-related quality of life (HRQoL) and fatigue are known to be associated with IBD activity and musculoskeletal complaints. The aim of this study was to determine the association between spondyloarthritis, arthralgia, or back pain and the patient-reported outcomes of HRQoL and fatigue in IBD patients 20 years after their diagnosis., Methods: The IBSEN cohort was followed prospectively for 20 years. At the 20-year follow-up, the patients answered detailed questionnaires regarding rheumatological manifestations, intestinal symptoms, HRQoL, and fatigue. Multiple regression analyses were used to evaluate associations between spondyloarthritis or joint symptoms and HRQoL or fatigue. Sex, IBD diagnosis, and age were included in all the multiple regression models, in addition to other clinically relevant confounders., Results: In total, 441 patients (94%) completed the questionnaires at the 20-year follow-up. The criteria for spondyloarthritis (axial or peripheral) were fulfilled in 158 patients (36%), current back pain during the previous 3 months was reported by 79 patients (18%), and current arthralgia was reported by 178 patients (40%). Current back pain and arthralgia were independently associated with lower HRQoL, higher levels of fatigue, and chronic fatigue. A diagnosis of spondyloarthritis was not associated with reduced HRQoL or fatigue when adjusted for possible confounders., Conclusions: Current joint symptoms in IBD patients 20 years after diagnosis were associated with poorer HRQoL, higher levels of fatigue, and chronic fatigue, whereas spondyloarthritis did not impact HRQoL or fatigue negatively in this cohort., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background : Pain and vitamin D deficiency are common in inflammatory bowel disease (IBD). Disease activity, fatigue, frequent relapses, prior surgery and psychological factors all seem to influence the experience of pain in IBD. Vitamin D deficiency has been associated with muscle and skeletal pain. This study aimed to determine whether there is an association between vitamin D deficiency and severity of pain in patients with IBD, and to investigate the influence of other socio-demographic and psychological variables on the experience of pain. Methods : Patients with IBD were recruited from nine hospitals in Norway in a multicenter cross-sectional study. The Brief Pain Inventory (BPI) questionnaire was used to measure pain. Disease activity was assessed using clinical disease activity indices, C-reactive protein (CRP) and fecal calprotectin. Regression models were fitted to explore a possible association between 25-hydroxyvitamin D and pain severity. Results : Of 407 patients included in the analyses, 229 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency was present in half (203/407) of patients. Presence of pain was reported by 76% (309/407). More severe pain was associated with female gender and increased disease activity scores, but not with increased CRP or fecal calprotectin. In CD, patients without prior intra-abdominal surgery reported more severe pain. In multivariate analyses, there was no association between 25-hydroxyvitamin D and pain severity. Conclusions : In this study, no significant association between pain severity and vitamin D deficiency was revealed in patients with IBD., Competing Interests: Frigstad SO reports a research grant from Pharmacosmos AS, during the conduct of the study; personal fees from Tillotts Pharma, Pharmacosmos AS, Janssen-Cilag, Pfizer, Takeda, Intercept Pharma, and Abbvie, outside the submitted work. Høivik ML reports personal fees from MSD, Tillotts Pharma, Abbvie, Takeda and MEDA, outside the submitted work, and investigator initiated research grants, outside the submitted work. Jelsness-Jørgensen LP reports an unrestricted research grant from Tillotts Pharma, during the conduct of the study. The other authors state no conflicts of interest.

Background and Aims: The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness., Methods: This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy., Results: In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients., Conclusion: Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.

Objectives: Peripheral arthritis and related musculoskeletal manifestations, often classified as peripheral spondyloarthritis, are frequently seen in patients with inflammatory bowel disease (IBD). Few long-term studies have reported on the prevalence of these conditions. The aim of this study was to determine the prevalence of IBD-related peripheral arthritis and peripheral spondyloarthritis in IBD patients during 20 years of disease course, and to assess whether these conditions were associated with the intestinal IBD severity and activity., Materials and Methods: In an inception cohort (the IBSEN study), IBD patients were followed prospectively for 20 years. At the 5 year follow-up the patients underwent a rheumatological examination and at the 20 year follow-up they completed a questionnaire with identical questions. When peripheral arthritis was characteristic and not explained by other specific diagnoses, it was defined as IBD-related peripheral arthritis. The Assessment of Spondyloarthritis International Society criteria were used to define peripheral spondyloarthritis, including patients with peripheral arthritis, enthesitis and/or dactylitis., Results: After 20 years of follow-up, 441 patients were included (296 ulcerative colitis and 145 Crohn's disease). The prevalence of IBD-related peripheral arthritis was 17.2% and peripheral spondyloarthritis 27.9% during the disease course. IBD severity and activity were not different between those with a history of IBD-related peripheral arthritis or peripheral spondyloarthritis and those without. A higher proportion of women had IBD-related peripheral arthritis and peripheral spondyloarthritis., Conclusion: During 20 years of disease course, more than every sixth patient had suffered from IBD-related peripheral arthritis and every fourth from peripheral spondyloarthritis.

Aim: To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD)., Methods: IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance., Results: In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients., Conclusion: In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Background and Aims: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data., Methods: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010-2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis., Results: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn's disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway's health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD., Conclusions: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway's health regions during the three first years after IBD diagnosis.

Background and Aims: Long-term data regarding switching from originator infliximab to biosimilar CT-P13 are sparse. Concerns about increased immunogenicity after switching have been raised. We aimed to study the effectiveness, safety and immunogenicity after switching from originator infliximab to CT-P13 in a real-world IBD population with 18 months prospective follow-up., Methods: All adult IBD patients treated with originator infliximab at the Department of Gastroenterology, Oslo University Hospital, were switched to CT-P13 and followed prospectively for 18 months. The primary endpoints were (i) the proportion of patients remaining on CT-P13 18 months after switching and (ii) immunogenicity during 18 months after switching. The secondary endpoints included (i) adverse events, (ii) changes in disease activity, C-reactive protein, anaemia, faecal calprotectin, infliximab dose and interval and p-infliximab., Results: In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. Altogether, 130 (91%) remained on CT-P13 throughout 18 months. Two patients developed ADAs at moderate level and discontinued CT-P13. Another 10 patients discontinued CT-P13 (two due to loss of response without ADAs, four due to adverse events, and four in remission and a personal wish to stop). There was no overall change in disease activity scores or in the other studied variables except for p-infliximab, which increased significantly., Conclusions: The present study provides valuable evidence for the safety and effectiveness of switching from originator to biosimilar infliximab over a prolonged period of 18 months and demonstrates that switching was well tolerated and did not affect the long term clinical outcome.

Background: Anti-tumor necrosis factor α (anti-TNF-α) is important in the treatment of inflammatory bowel disease, but some patients experience only a partial response. In these patients, a combination of anti-TNF-α and vedolizumab (VDZ) may act as a bridge until the full VDZ effect occurs. At present, clinical data on combination treatment with anti-TNF-α and VDZ are not available. The aim of this case series was to evaluate the safety and clinical response of combination therapy with anti-TNF-α and VDZ in clinical practice., Methods: All patients started on combination treatment with anti-TNF-α and VDZ from November 2015 to July 2016 were prospectively followed for at least 12 months., Results: Six patients with ulcerative colitis and four patients with Crohn's disease received combination treatment. These patients were followed for a median of 1712-20 months. No more adverse events than expected with anti-TNF-α alone were observed during combination treatment. At the end of follow-up, all patients were in clinical remission, and 8 patients could discontinue anti-TNF-α treatment and receive VDZ monotherapy. Two of the patients with Crohn's disease required combination treatment throughout follow-up to obtain sustained remission., Conclusion: Our findings suggest that combination treatment with anti TNF-α and VDZ is safe and might represent a long-term treatment option in selected patients.

Background and Aims: An increased prevalence of irritable bowel syndrome [IBS]-like symptoms has been reported in patients with ulcerative colitis [UC]. Whether ongoing inflammation increases the prevalence of such symptoms is unknown. The aims of this study were to determine the prevalence of IBS-like symptoms in a population-based cohort of UC patients 20 years after diagnosis, and to assess the possible association between such symptoms and ongoing inflammation., Methods: Patients diagnosed with UC between 1990 and 1994, in a geographically well-defined area, were included in a prospective follow-up study, and IBS symptoms according to Rome III criteria were recorded 20 years after diagnosis. The patients underwent colonoscopy with biopsies and/or the level of faecal calprotectin was analysed., Results: A total of 260 patients answered the Rome III questionnaire. The overall prevalence of IBS-like symptoms was 27%. In patients who had no signs of inflammation in colonic biopsies [n = 96] [deep remission], the prevalence was 29%. No difference in prevalence of IBS-like symptoms was found between patients with ongoing inflammation and patients in deep remission., Conclusions: IBS-like symptoms in UC patients are frequent after 20 years of disease. Deep remission did not change the frequency of IBS-like symptoms.

Background: Patients with inflammatory bowel disease [IBD] often suffer from rheumatic manifestations, including inflammatory back disorders. The prevalence of these disorders late in the course of IBD is poorly investigated. The aim of this study was to estimate the prevalence of inflammatory back disorders in patients with IBD 20 years after diagnosis, and to investigate possible associations with IBD severity, HLA-B27, and the NOD2 genotype., Methods: A population-based cohort [the IBSEN study] was followed prospectively for 20 years. Information covering IBD activity and rheumatic diseases was collected at the regular follow-ups. HLA-B27 and NOD2 were analysed as present or absent., Results: At 20 years, 599 members of the original cohort were alive, of whom 470 [78.5%] were investigated [314 ulcerative colitis and 156 Crohn's disease patients]. Ankylosing spondylitis was diagnosed in 21 patients [4.5%], axial spondyloarthritis was diagnosed in 36 patients [7.7%], and inflammatory back pain was diagnosed in 54 patients [11.5%]. Chronic back pain [back pain > 3 months] was present in 220 patients [46.8%]. HLA-B27 was associated with ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain, whereas no significant association was found for NOD2. A more chronic IBD course was associated with axial spondyloarthritis., Conclusions: Our data revealed a high prevalence of ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain 20 years after the IBD diagnosis. HLA-B27 but not NOD-2 was a predisposing factor for the inflammatory back disorders in IBD patients. Axial spondyloarthritis was associated with a more chronic active IBD disease course., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD., Methods: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives., Results: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS., Conclusions: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS.

Background and Aims: Whether patients with inflammatory bowel diseases [IBDs] have increased risk of developing cancer has been debated. The aims of the study were to determine the prevalence of intestinal/extraintestinal cancers in an IBD cohort 20 years after diagnosis and to assess whether these patients had an increased cancer-specific risk compared with a matched control population., Methods: Patients with ulcerative colitis [UC] and Crohn's disease [CD] diagnosed 1990-1993 have been prospectively followed up for 20 years. Follow-up visits were carried out 1, 5, 10, and 20 years after inclusion. Data on all cancer cases, deaths, and causes of death were collected from the Cancer Registry of Norway and from the Norwegian Cause of Death Registry., Results: In all, 756 patients [519 UC and 237 CD] were diagnosed with IBD. Increased risk of cancer was seen in UC patients (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.08-1.81, p < 0.01), but not in CD patients [HR = 1.23, 95% CI 0.80-2.03, p = 0.30]. Stratified by gender, our data revealed a statistically increased risk for all cancers only in male UC patients compared with the controls [HR = 1.51, 95% CI 1.08-2.11, p = 0.017]. In both groups breast cancer was seen more often than expected., Conclusions: Male UC patients display an increased risk of development of colorectal cancer and, also all cancers combined, compared with the controls. In both UC and CD, standardized incidence ratio for breast cancer was increased., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Objective: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease., Design: We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, Q FDR <0.20) in both panels were reported, followed by a combined comparison of all samples against UC., Results: Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78., Conclusions: Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Aims: A biosimilar version of infliximab [CT-P13/Remsima®] recently entered the European market. The clinical data on its use in inflammatory bowel disease [IBD] are sparse, especially on switching from the originator Remicade®. In this study, we aimed to prospectively investigate the feasibility, safety and immunogenicity of switching from Remicade to Remsima in a real-life IBD population., Methods: All adult patients who were treated with Remicade in the Department of Gastroenterology at Oslo University Hospital were switched to Remsima. The follow-up lasted for 6 months. In addition, a retrospective registration was performed with a start time of 6 months before switching drugs. The primary endpoints were [i] the proportion of patients remaining on medication 6 months after switching and [ii] adverse events during the 6 months after switching. The secondary endpoints included [i] disease activity scores [Harvey-Bradshaw Index and Partial Mayo Score], C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval, and p-infliximab and [ii] the development of antidrug antibodies., Results: In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. The large majority [97%] remained on the medication throughout follow-up. A low number of adverse events were observed. No change in disease activity, C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval or p-infliximab was detected. Three patients developed new detectable antidrug antibodies., Conclusions: Switching from Remicade to Remsima was feasible and with few adverse events, including very limited antidrug antibody formation and loss of response., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Objective: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn's disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort., Methods: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses., Results: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p < .001, and CD 17.5 versus 13.3, p < .001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression., Conclusion: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.

Background: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use., Conclusions: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics., (© 2017 S. Karger AG, Basel.)

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by low immunoglobulin (Ig)G and IgA, and/or IgM. In addition to bacterial infections, a large subgroup has noninfectious inflammatory and autoimmune complications. We performed 16S ribosomal RNA-based profiling of stool samples in 44 CVID patients, 45 patients with inflammatory bowel disease (disease controls), and 263 healthy controls. We measured plasma lipopolysaccharide (LPS) and markers of immune cell activation (i.e., soluble (s) CD14 and sCD25) in an expanded cohort of 104 patients with CVID and in 30 healthy controls. We found a large shift in the microbiota of CVID patients characterized by a reduced within-individual bacterial diversity (alpha diversity, P<0.001) without obvious associations to antibiotics use. Plasma levels of both LPS (P=0.001) and sCD25 (P<0.0001) were elevated in CVID, correlating negatively with alpha diversity and positively with a dysbiosis index calculated from the taxonomic profile. Low alpha diversity and high dysbiosis index, LPS, and immune markers were most pronounced in the subgroup with inflammatory and autoimmune complications. Low level of IgA was associated with decreased alpha diversity, but not independently from sCD25 and LPS. Our findings suggest a link between immunodeficiency, systemic immune activation, LPS, and altered gut microbiota.

Background & Aims: The prevalence of primary sclerosing cholangitis (PSC) among patients with inflammatory bowel disease (IBD) is unclear. Patients with IBD might be screened for PSC using magnetic resonance cholangiography (MRC). We aimed to estimate the frequency and distribution of MRC-detected lesions that indicate PSC in patients with IBD 20 years after their initial diagnosis and to identify clinical characteristics associated with these findings., Methods: We performed a follow-up analysis of a population-based cohort of 756 patients in South-Eastern Norway diagnosed with IBD from January 1, 1990 through December 31, 1993. Of these subjects, 470 attended a follow-up evaluation 20 years later in which they were offered routine clinical blood testing and ileocolonoscopy; 322 were screened by MRC (222 with ulcerative colitis and 100 with Crohn's disease). Two radiologists independently evaluated results from the MRC examinations., Results: In the MRC examination, 24 patients (7.5%) were found to have PSC-like lesions; only 7 of these patients (2.2%) were known to have PSC. One patient was initially missed and 1 had small-duct PSC, so the final prevalence of PSC was 8.1%. Extensive colitis, a high prevalence of colectomy, and chronic and continuous symptoms of IBD occurred in significantly more patients with suspected PSC than without PSC (P = .029, P = .002, and P = .012, respectively). Among patients with subclinical features of PSC, the MRC progression score for PSC increased when they were re-examined after a median 3.2 years (P = .046)., Conclusions: Using MRC analysis of patients with long-term IBD, we found the prevalence of PSC to be around 3-fold higher than that detected based on symptoms. Sixty-five percent of patients had subclinical PSC associated with progressive IBD, with no biochemical abnormalities and mild disease, based on radiology findings. PSC appears to progress in patients with subclinical disease, but long-term outcomes are not known., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Ulcerative colitis (UC) is characterized by chronic inflammation of the large bowel in genetically susceptible individuals exposed to environmental risk factors. The disease course can be difficult to predict, with symptoms ranging from mild to severe. There is no generally accepted definition of severe UC, and no single outcome is sufficient to classify a disease course as severe. There are several outcomes indicating a severe disease course, including progression of the disease's extension, a high relapse rate, the development of acute severe colitis, colectomy, the occurrence of colorectal cancer and UC-related mortality. When evaluating a patient's prognosis, it is helpful to do so in relation to these outcomes. Using these outcomes also makes it easier to isolate factors predictive of severe disease. The aims of this article are to evaluate different disease outcomes and to present predictive factors for these outcomes.

Background: The best way to obtain knowledge about the natural history, including mortality, of ulcerative colitis (UC) is to conduct a longitudinal, population-based, prospective study. The aims of this study were to calculate the mortality rates and causes of death in patients with UC., Methods: A prospective, population-based, longitudinal cohort study was conducted in South-Eastern Norway. A total of 519 patients (51.4% men) with UC were included over a 4-year period. A gastroenterologist from a university hospital reviewed the clinical information of all of the patients. Mortality data were retrieved from the Cause of Death Registry and from Statistics Norway., Results: No statistically significant increases in total mortality or cause-specific mortality between the patients with UC and the controls were found., Conclusions: The present 20-year population-based cohort study revealed a good prognosis regarding the mortality, which partially might be explained by the patients' coverage by a generally well-functioning health care system.

Background: Chronic inflammatory bowel disease (IBD) negatively affects the patient's health-related quality of life (HRQoL). Only a few population-based studies have compared the HRQoL of patients with the background population. The aim of this study was to evaluate the HRQoL in a European cohort of patients with ulcerative colitis and Crohn's disease 10 years after diagnosis (European Collaborative study group of Inflammatory Bowel Disease) compared with the national background population in each country and to assess possible country-specific differences., Methods: Patients with IBD from 7 European countries were invited to a follow-up visit 10 years after their diagnosis of IBD. We assessed their clinical and demographic data, including the generic HRQoL questionnaire short form health survey-36. Countrywise comparison with the background population was performed with z-scores using the Cohen's effect size index., Results: Seven hundred sixty-nine patients were eligible for the study. We registered statistically significant and clinically relevant decreases in the short form health survey-36 dimensional scores in patients with symptoms at the time of follow-up and for patients reporting sick leave during the previous year or having received disablement pension. In the Netherlands and Norway, there was a moderate difference between the patients with IBD and the background population for the general health dimension., Conclusions: Overall, the HRQoL was not reduced in the IBD cohort compared with the background populations. However, in addition to older age and female gender, current symptoms at follow-up, disablement pension, and sick leave during the previous year were significantly associated with a reduced HRQoL in patients with IBD.