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

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

Subcutaneous Vedolizumab Treatment in a Real-World Inflammatory Bowel Disease Cohort Switched From Intravenous Vedolizumab: Eighteen-Month Prospective Follow-up Study.

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.

Risk of Cancer in Patients With Crohn's Disease 30 Years After Diagnosis (the IBSEN Study).

Background: Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types. Methods: The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population. Results: In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively). Conclusions: After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.

Incidence of cancer in patients with ulcerative colitis 30 years after diagnosis (the IBSEN study).

OBJECTIVES: Patients with ulcerative colitis (UC) have shown an increased risk for colorectal cancer, hepatobiliary, hematologic, and skin cancers, but updated long-term data is needed. This study aimed to estimate the risk of cancer in patients with UC compared to the general Norwegian population, in a population-based cohort (the IBSEN study), 30 years after diagnosis; and to identify possible risk factors associated with cancer. METHODS: The IBSEN cohort prospectively included all incident patients between 1990 and 1993. Cancer incidence data were obtained from the Cancer Registry of Norway. The overall and cancer-specific hazard ratios (HR) were modelled using Cox regression. Standardized incidence ratios were estimated compared to the general population. RESULTS: In total, the cohort included 519 patients, and 83 cases were diagnosed with cancer. There was no statistically significant difference in the overall cancer risk (HR = 1.01, 95% CI: [0.79-1.29]) and colorectal cancer risk (HR = 1.37, 95% CI: [0.75-2.47]) between patients and controls. The incidence of biliary tract cancer was higher than expected (SIR = 9.84, 95%CI: [3.19-20.15]), especially when UC patients suffered from primary sclerosing cholangitis. Male UC patients were also more at risk of being diagnosed with hematologic malignancies (HR = 3.48, 95% CI: [1.55-7.82]). Being prescribed thiopurines was associated with a higher risk of cancer (HR = 2.03, 95% CI: [1.02-4.01]). CONCLUSIONS: At 30 years after diagnosis, the risk of all cancer in patients with UC was not significantly increased compared with the general population. However, the risks of biliary tract cancer and hematologic cancers were increased, particularly in male patients.

The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission.

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.

The Real-World Global Use of Patient-Reported Outcomes for the Care of Patients With Inflammatory Bowel Disease.

Background: Many patient-reported outcomes (PROs) have been developed for inflammatory bowel disease (IBD) without recommendations for clinical use. PROs differ from physician-reported disease activity indices; they assess patients' perceptions of their symptoms, functional status, mental health, and quality of life, among other areas. We sought to investigate the current global use and barriers to using PROs in clinical practice for IBD. Methods: A cross-sectional survey was performed. An electronic questionnaire was sent to an international group of providers who care for patients with IBD. Results: There were 194 respondents, including adult/pediatric gastroenterologists, advanced practice providers, and colorectal surgeons from 5 continents. The majority (80%) use PROs in clinical practice, 65% frequently found value in routine use, and 50% frequently found PROs influenced management. Thirty-one different PROs for IBD were reportedly used. Barriers included not being familiar with PROs, not knowing how to incorporate PRO results into clinical practice, lack of electronic medical record integration, and time constraints. Most (91%) agreed it would be beneficial to have an accepted set of consistently used PROs. The majority (60%) thought that there should be some cultural differences in PROs used globally but that PROs for IBD should be consistent around the world. Conclusions: PROs are used frequently in clinical practice with wide variation in which are used and how they influence management. Education about PROs and how to use and interpret an accepted set of PROs would decrease barriers for use and allow for global harmonization.

Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring.

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.

Mortality in Patients with Inflammatory Bowel Disease: Results from 30 Years of Follow-up in a Norwegian Inception Cohort (the IBSEN study).

BACKGROUND AND AIMS: Patients with longstanding inflammatory bowel disease [IBD] may be at an increased risk of death compared to the general population, especially elderly patients. The Inflammatory Bowel South-Eastern Norway [IBSEN] study has previously detected a small but not statistically significant increase in mortality 20 years after diagnosis. The aim of this study was to evaluate the overall and cause-specific mortality at 30 years of follow-up. METHODS: The IBSEN cohort included 519 incident patients with ulcerative colitis [UC] and 237 patients with Crohn's disease [CD] between 1990 and 1993, each matched with five controls. Death certificate data were obtained from the Norwegian Cause of Death Registry. The underlying causes of death were categorized into five groups: all cancers, gastrointestinal cancers, cardiovascular diseases, infections and all other causes. Hazard ratios [HRs] were modelled using Cox regression. RESULTS: There was no statistically significant difference in the overall mortality rates. However, in patients with CD, male sex (HR = 1.65 [95% CI: 1.04-2.62]), onset after 40 years of age (HR = 1.72 [1.19-2.48]), colonic disease (HR = 1.57 [1.05-2.35]) and penetrating behaviour (HR = 3.3 [1.41-7.76]) were clinical factors associated with an increased mortality. IBD patients were at a higher risk of death due to cardiovascular disease: HR = 1.51 [1.10-2.08] for UC and 2.04 [1.11-3.77] for CD. When taking into account both the underlying and the immediate cause of death, infection was more frequent in patients with IBD. CONCLUSIONS: Overall, all-cause mortality rates were similar between patients with IBD and controls. However, clinicians should remain alert to cardiovascular diseases and infections, particularly in specific subgroups of CD patients.

The impact of restrictions on psychological outcomes in patients with inflammatory bowel disease on biological treatment during the coronavirus pandemic in Norway.

PURPOSE: The coronavirus (COVID-19) pandemic restrictions have led to changes in the follow-up routine of patients in outpatient clinics at hospitals in Norway. The purpose of this study was to assess possible associations between psychological health and concerns regarding COVID-19 societal and hospital restrictions in patients with inflammatory bowel disease on biological therapy. METHODS: Patients with IBD (≥ 18 years) undergoing biological treatment (TNF-alpha inhibitor, ustekinumab, vedolizumab) for IBD were recruited from an IBD outpatient clinic in Norway. Data were collected through self-report, including questions covering concerns regarding their disease, medical therapy, and follow-up during the pandemic, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 questionnaire (GAD-7). Multiple logistic regression with backward conditional selection was fitted to examine associations between patients' depression and anxiety levels and their concerns about COVID-19 restrictions, controlled for sociodemographic and disease-related factors. RESULTS: Five-hundred and six patients were included in this study. General condition, self-isolation, employment status, fear of visiting the hospital, and changes to patients' appointments made by the hospital were independently associated with higher levels of depression. Female gender, experiencing symptoms of COVID-19, self-isolation, experiencing an increased risk of COVID-19 because of IBD, being afraid to visit the hospital because of COVID-19 restrictions, and having their appointment cancelled due to COVID-19 were independently associated with higher anxiety levels. CONCLUSION: Concerns about physical health and societal and hospital restrictions were associated with anxiety and depression in patients with IBD undergoing biological treatment. The findings will help facilitate healthcare services for patients with IBD in outpatient clinics and develop guidelines for follow-up.

[Iron deficiency in patients with acute and chronic heart failure - a simple algoritm]. / Bedömning och behandling av järnbrist hos hjärtsviktspatienter.

Iron deficiency, defined as ferritin <100 µg/L or ferritin 100-299 µg/L if the transferrin saturation is <20 %, with or without anaemia is a common comorbidity in patients with acute and chronic heart failure. International and Swedish guidelines recommend treatment of iron deficiency with intravenous iron in patients with symptomatic heart failure and ejection fraction <50 %. Controlled studies document positive effects from treatment with iron carboxymaltose on symptoms, quality of life, functional parameters and risk of hospitalisation. We present a simple algoritm based on published data to help the responsible physician to manage these patients in clinical practice.

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

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

The multidimensional fatigue inventory (MFI-20): psychometrical testing in a Norwegian sample of inflammatory bowel disease (IBD) patients.

OBJECTIVES: To evaluate the psychometric properties of the Norwegian version of the multidimensional fatigue inventory (MFI-20) in patients with inflammatory bowel disease. METHODS: Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the MFI-20, as well as the Fatigue Questionnaire (FQ). In addition to a confirmatory factor analysis, validity, reliability, test-retest and responsiveness were evaluated. RESULTS: In total, 410 patients were included. The Norwegian MFI-20 had an acceptable model fit when compared to the original five-dimensional structure. A positive correlation was observed between the dimensions of MFI-20 and the FQ. MFI-20 scores increased according to subjective disease activity, but no differences were observed when using a calprotectin cut-off < or > =250 µg/g mg/kg. All MFI-20 dimensions except 'reduced motivation' in both ulcerative colitis (UC) and Crohn's disease (CD) patients had alpha Cronbach alpha values ≥70, and test-retest reliability revealed good to excellent values. Merely one dimension (Reduced activity) in UC patients reporting improvement did not reach the threshold for acceptable responsiveness according to Guyatt statistics. CONCLUSIONS: The Norwegian version of MFI-20 is valid, reliable and responsive. The instrument can safely be used in studies using fatigue as an endpoint.

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

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

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

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

Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact.

BACKGROUND: High-dose intravenous iron is an effective treatment option for iron deficiency (ID) or ID anaemia (IDA) in inflammatory bowel disease (IBD). However, treatment with ferric carboxymaltose (FCM) has been associated with the development of hypophosphatemia. AIM: To investigate mechanisms behind the development of hypophosphatemia after intravenous iron treatment, and disclose symptoms and clinical manifestations related to hypophosphatemia short-term. METHODS: A prospective observational study of adult IBD patients with ID or IDA was conducted between February 1, 2017 and July 1, 2018 at two separate university hospitals in the southeast region of Norway. Patients received one dose of 1000 mg of either FCM or ferric derisomaltose (FDI) and were followed for an observation period of at least 7 wk. Blood and urine samples were collected for relevant analyses at baseline, week 2 and at week 6. Clinical symptoms were assessed at the same timepoints using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire. RESULTS: A total of 106 patients was available for analysis in this study. The FCM treatment group consisted of 52 patients and hypophosphatemia was present in 72.5% of the patients at week 2, and in 21.6% at week 6. In comparison, the FDI treatment group consisted of 54 patients and 11.3% of the patients had hypophosphatemia at week 2, and 3.7% at week 6. The difference in incidence was highly significant at both week 2 and 6 (P < 0.001 and P < 0.013, respectively). We observed a significantly higher mean concentration of intact fibroblast growth factor 23 (P < 0.001), a significant rise in mean urine fractional excretion of phosphate (P = 0.004), a significant decrease of 1,25-dihydroxyvitamin D (P < 0.001) and of ionised calcium levels (P < 0.012) in the FCM-treated patients compared with patients who received FDI. No clinical symptoms could with certainty be related to hypophosphatemia, since neither the respiratory function test, SF-36 (36-item short form health survey) or the visual analogue scale scores resulted in significant differences between patients who developed hypophosphatemia or not. CONCLUSION: Fibroblast growth factor 23 has a key role in FCM induced hypophosphatemia, probably by inducing loss of phosphate in the urine. Short-term clinical impact of hypophosphatemia was not demonstrated.

Patients with inflammatory bowel disease on immunosuppressive drugs: perspectives' on COVID-19 and health care service during the pandemic.

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) have experienced changes to the routine management because of the SARS-CoV-2 pandemic. The aim of this study was to examine patients with IBD's adherence to the restrictions imposed by society and the hospital, worries and concerns regarding medical treatment and clinical follow-up under the pandemic. METHODS: IBD patients (≥18 years) at the outpatient clinic at Oslo University Hospital were included and answered a self-report questionnaire including concerns regarding their disease, medical therapy and follow-up during SARS-CoV-2 pandemic. RESULTS: In total, 522 IBD patients were included, 317 Crohn's disease, 205 ulcerative colitis, 386 patients <50 years. Eighteen percent were in obligatory quarantine, and more often patients <50 years compared to patients ≥50 years. Five patients tested positive to SARS- CoV-2. A higher proportion <50 years reported worries for their medical treatment and risk of COVID -19 disease compared to those ≥50 years. Forty percent avoided family, two-thirds avoided friends, and 4% cancelled their scheduled consultation at the hospital. The hospital changed physical consultation to telephone consultation for 15% of the patients. The preferred follow-up was physical consultation. A higher proportion of the patients <50 years preferred telephone consultation compared to those ≥50 years. Four out of five IBD patients were satisfied with the information about their IBD and COVID-19. CONCLUSIONS: SARS-CoV-2 pandemic affects the daily lives for patients with IBD. It is important to develop evidence-base guidelines in follow-up and treatment, as well as patient information about COVID-19and IBD.

Outcome of Ulcerative Colitis 20 Years after Diagnosis in a Prospective Population-based Inception Cohort from South-Eastern Norway, the IBSEN Study.

BACKGROUND AND AIMS: The long-term course of ulcerative colitis [UC] is difficult to predict. Mortality, colectomy, cancer, and hospitalisation represent hard outcomes of disease. Moreover, knowledge on the risk of relapses and need for potent medication add important information about living with UC. We aimed to evaluate the course and prognosis of UC during the first 20 years after diagnosis, and to identify early prognostic risk factors. METHODS: From 1990 to 1994, a population-based inception cohort of patients with inflammatory bowel disease was enrolled in South-Eastern Norway. A systematic follow-up [FU] was conducted at 1,5, 10, and 20 years after diagnosis. Clinical outcomes were recorded continuously, and possible relationships between early disease characteristics and outcomes were analysed using multiple regression analysis. RESULTS: Among 519 UC patients, 119 died, 60 were lost to FU, and 340 were included in the FU cohort. The 20-year cumulative risk of colectomy was 13.0% (95% confidence interval [CI] [11.4-14.6]). Extensive colitis at diagnosis was independently associated with an increased risk of colectomy compared with proctitis (hazard ratio [HR] = 2].8, 95% CI [1.3-6.1]). In contrast, mucosal healing at 1-year FU was independently associated with reduced risk of colectomy [HR = 0.4, 95% CI [0.2-0.8]), and inversely associated with subsequent risk of relapse [adjusted HR = 0.5, 95% CI [0.3-0.7]). CONCLUSIONS: The overall risk of colectomy in our cohort was lower than expected from previous studies, although considerable for patients with extensive colitis at diagnosis. Early mucosal healing was associated with better disease outcomes 20 years after diagnosis.

Comprehensive assessment of ECM turnover using serum biomarkers establishes PBC as a high-turnover autoimmune liver disease.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are phenotypically distinct autoimmune liver diseases that progress to cirrhosis and liver failure; however, their histological fibrosis distribution differs. We investigated the extracellular matrix (ECM) profiles of patients with PSC, PBC, and AIH to establish whether the diseases display differential patterns of ECM turnover. METHODS: Serum samples were retrospectively collected from the UK (test cohort; PSC n = 78; PBC n = 74; AIH n = 58) and Norway (validation cohort; PSC n = 138; PBC n = 28; AIH n = 27). Patients with ulcerative colitis without liver disease (n = 194) served as controls. We assessed specific serological biomarkers of ECM turnover: type III and V collagen formation (PRO-C3, PRO-C5), degradation of type III and IV collagen (C3M, C4M), biglycan (BGM) and citrullinated vimentin (VICM). RESULTS: Most of the ECM markers showed elevated serum levels in PBC compared with PSC or AIH (p <0.01). PRO-C3 correlated well with liver stiffness and showed the most striking differences between advanced and non-advanced liver disease; several of the other ECM markers were also associated with stage. PRO-C3 and other ECM markers were inversely associated with ursodeoxycholic acid treatment response in PBC and remission in AIH. All ECM remodelling markers were significantly elevated (p <0.05) in patients with PSC, PBC, or AIH compared with ulcerative colitis. CONCLUSIONS: In this first study comparing ECM turnover in autoimmune liver diseases, we found increased ECM turnover in PBC compared with either PSC or AIH. The study indicates that ECM remodelling is different in PSC, PBC, and AIH, suggesting differing opportunities for therapeutic intervention. LAY SUMMARY: The level of scarring is linked to prognosis in autoimmune liver diseases such as primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis; hence, the scarring process is a possible target for novel therapy. Investigating the scarring process using highly specific technology, we show that the scarring process is different between the 3 autoimmune liver diseases, and this may have important implications for the development of medical treatment.

Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials.

BACKGROUND: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. OBJECTIVE: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials. PATIENTS AND METHODS: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period. RESULTS: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events. CONCLUSION: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02148640.