Risk of malignancy in a high-incidence population-based cohort of Faroese patients with inflammatory bowel disease from 1960 to 2020 - a Faroese IBD cohort study.

BACKGROUND: The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. METHODS: This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population's age- and sex-specific cancer incidence rates, retrievable from NORDCAN. RESULTS: The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50-59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02-2.99) as did UC patients diagnosed with IBD at 50-59 (SIR 2.1; 95% CI, 1.10-3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. CONCLUSIONS: This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable.

Cancer survival in the Faroe Islands over the last 50 years compared to the other Nordic countries.

As sustained development in cancer treatment protocols have led to improved survival in most areas of the world, surveillance is needed to ensure that small populations follow suit. Our study reports age-standardized relative cancer survival in the Faroe Islands compared to the other Nordic countries. We present 1- and 5-year survival estimates and corresponding 95% confidence intervals for the Faroe Islands and compare them with estimates for the Nordic countries. The data for this article has been obtained through the NORDCAN collaboration (2019 data). Age-standardized relative survival was estimated using shared R codes on individual-level data within each country. Ten-year calendar inclusion periods were used in addition to the usual 5-year calendar periods to include cancer sites with few cases, which is especially beneficial to the smaller populations. The primary findings were that 1- and 5-year survival were consistently lower in the Faroes for the summary group all sites but non-melanoma skin cancer for both women and men. Further, 5-year survival was lower for women with ovarian cancer and men with lung cancer than in other Nordic countries. Previously, breast cancer survival was low in the Faroes but has improved to a comparable level over the last few years. Colorectal cancer survival was relatively high for both sexes. The reported estimates in this article call for further research to investigate the cancers with lower survival and should call for actions to improve the survival of Faroese cancer patients.

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

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

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

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

The Incidence and Prevalence of Inflammatory Bowel Disease Continues to Increase in the Faroe Islands - A Cohort Study from 1960 to 2020.

BACKGROUND AND AIMS: The highest reported incidence rate of inflammatory bowel disease [IBD], and especially of ulcerative colitis [UC], is found in the Faroe Islands. This study aimed to assess the incidence rate and temporal trends in prevalence over six decades. METHODS: All incident and prevalent patients diagnosed with IBD between 1960 and 2020 from the nationwide and population-based Faroese IBD cohort were included in this study. All patients fulfilled the Copenhagen Diagnostic Criteria. RESULTS: Overall, 873 individuals were diagnosed with IBD during the study period, 559 [64%] with UC, 151 [17%] with Crohn's disease, and 163 [19%] with IBD unclassified. A total of 59 patients had paediatric-onset IBD. The incidence of IBD continued to increase throughout the study period, as the age-standardized incidence rate started at 8 per 100 000 person-years [py] [European Standard Population, ESP] in 1960-79 and reached 70 by 2010-20. In 2021, the age-standardized period prevalence was 1414 per 100 000 persons. The IBD incidence was unevenly distributed among the islands with Sandoy having the highest rate of 106 per 100 000 py in 2010-2020. CONCLUSIONS: The incidence of IBD continues to increase in the Faroe Islands, mainly driven by UC. The incidence shows an uneven geographical distribution, which suggests an adverse interaction between unknown environmental factors and genetic traits. The prevalence in 2021 corresponded to 1.3% of the Faroese population. Environmental risk factors are suspected to impact this homogeneous high-risk population; however, the reason for this is unclear.

Mortality of Patients With Inflammatory Bowel Disease in the Faroe Islands From 1966-2020.

BACKGROUND: Increased mortality rates have been found in patients suffering from inflammatory bowel disease (IBD). The Faroe Islands have the highest occurrence of IBD, mainly ulcerative colitis (UC). This study investigated mortality of patients with IBD compared with the general Faroese population. METHODS: All patients diagnosed with IBD from 1966-2020 were included, as well as population mortality data. All-cause and cause-specific mortality in the IBD cohort was compared with the population by standardized incidence ratios (SIRs). Risk factors for death within the cohort were assessed by hazard ratios (HRs) using Cox regression. RESULTS: Overall mortality was not increased in patients with Crohn's disease (CD; SIR 0.9; 95% confidence interval [CI], 0.56-1.35) or UC (SIR 1.0; 95% CI, 0.83-1.25). However, patients with UC had an elevated risk of dying from digestive diseases (SIR 4.3; 95% CI, 2.16-7.74). Patients with IBD had lower risk of death of cardiovascular diseases compared with the background population (SIR 0.7; 95% CI, 0.50-0.93). Risk factors for mortality included male gender, age at diagnosis, and use of steroids. Protective factors were use of 5-aminosalicylic acid (5-ASA), thiopurines, and biological treatment. CONCLUSIONS: No increased risk of all-cause mortality in patients with CD or UC was found in this nationwide study compared with the entire Faroese population over more than 5 decades. The risk of death due to digestive diseases was, however, increased in patients with UC, while mortality risk of cardiovascular diseases was lower in patients with IBD.

Increased mortality exists in IBD patients. The Faroe Islands have the highest occurrence in the world, though mortality risk in Faroese patients compared with the population is unknown. No increased overall risk was found, while mortality risk of digestive diseases was elevated.

A nationwide study of autoimmune liver diseases in the Faroe Islands: Incidence, prevalence, and causes of death 2004 - 2021.

Background and aims: Autoimmune liver diseases are rare diseases, and population-based studies on the epidemiology of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are sparse. We aimed to assess the incidence of AIH, PBC, and PSC in the Faroe Islands.Methods: All cases of AIH, PBC, and PSC diagnosed in the Faroe Islands between January 1st, 2004, and December 31st, 2021, were included in this nationwide registry-based cohort study. In addition, we searched all medical records to assess diagnostic criteria and cause of death.Results: The incidences of AIH, PBC, and PSC in the Faroe Islands were 5.2, 2.5 and 0.7 per 100,000 population per year, respectively. Point prevalence per 100,000 population on December 31st 2021, was 71.8 for AIH, 38.5 for PBC, and 11.0 for PSC. Nine AIH patients died after a median of 3 years, three died of hepatocellular carcinoma (HCC), and two died of liver failure. Five PBC patients died after a median of 7 years, one of HCC and one of liver failure. One PSC patient died of cholangiocarcinoma.Conclusion: The incidence and prevalence of AIH, PBC and PSC in the Faroe Islands are among the highest reported in population-based settings.

Similar Gut Bacterial Composition Between Patients With Ulcerative Colitis and Healthy Controls in a High Incidence Population: A Cross-sectional Study of the Faroe Islands IBD Cohort.

BACKGROUND: The Faroe Islands has the world's highest incidence of inflammatory bowel disease (IBD). Epidemiological studies have characterized this unique cohort and a decreased risk of developing IBD with emigration. Therefore, this well-characterized Faroese IBD cohort gives the opportunity to better understand this complex disease. This study represents the first investigation of the gut microbiota for the cohort. METHODS: This cross-sectional study consisted of 41 patients with established ulcerative colitis and 144 age- and sex-matched healthy controls recruited through the Faroe Genome project. Participants donated a 1-time fecal sample and completed questionnaires on food frequency, background health, and lifestyle. 16S rRNA amplicon sequencing of the V3-V4 region was performed followed by bioinformatic analysis of taxonomy and diversity metrics. RESULTS: The overall bacterial composition in both groups was dominated by Firmicutes and Bacteroidetes. No significant differences were found based on metrics of alpha or beta diversity. However, discriminatory analysis identified differential abundance of several indicator taxa in healthy controls and ulcerative colitis participants, whereas Akkermansia was completely absent from 27% of all study participants. Food frequency questionnaires revealed similar dietary patterns between the 2 groups. CONCLUSION: The similarity in bacterial community composition and absence of the beneficial Akkermansia genus in both groups raise further questions concerning the underlying susceptibility toward inflammatory disorders within this high-risk population. Results vary widely by study design and geographic location, which speaks to the need for regionally tuned reference groups and disease-based studies on the Faroe Islands.

The Faroe Islands has the world's highest incidence of IBD. This is the first investigation characterizing gut microbiota for this unique cohort. No significant differences were found between ulcerative colitis and healthy controls based on alpha or beta diversity.

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up. METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery. FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001). INTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease. FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study.

BACKGROUND AND AIMS: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort. METHODS: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. RESULTS: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8]. CONCLUSIONS: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.

BACKGROUND: The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. METHODS: Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). RESULTS: In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. DISCUSSION: In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.