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 cost burden of Crohn's disease and ulcerative colitis depending on biologic treatment status - a Danish register-based study.

BACKGROUND: Patients diagnosed with inflammatory bowel disease may be treated with biologics, depending on several medical and non-medical factors. This study investigated healthcare costs and production values of patients treated with biologics. METHODS: This national register study included patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between 2003 and 2015, identified in the Danish National Patient Register (DNPR). Average annual healthcare costs and production values were compared for patients receiving biologic treatment or not, and for patients initiating biologic treatment within a year after diagnosis or at a later stage. Cost estimates and production values were based on charges, fees and average gross wages. RESULTS: Twenty-six point one percent CD patients and ten point seven percent of UC patients were treated with biologics at some point in the study period. Of these, 46.4 and 45.5 % of patients initiated biologic treatment within the first year after diagnosis. CD and UC patients treated with biologics had higher average annual healthcare costs after diagnosis compared to patients not treated with biologics. CD patients receiving biologics early had lower production values both ten years before and eight years after treatment initiation, compared to patients receiving treatment later. UC patients receiving biologics early had lower average annual production values the first year after treatment initiation compared to UC patients receiving treatment later. CONCLUSIONS: CD and UC patients receiving biologic treatment had higher average annual healthcare costs and lower average annual production values, compared to patients not receiving biologic treatment. The main healthcare costs drivers were outpatient visit costs and admission costs.

Costs of electronic health vs. standard care management of inflammatory bowel disease across three years of follow-up-a Danish register-based study.

BACKGROUND: Costs of using eHealth in inflammatory bowel disease (IBD) management has only been assessed for short follow-up periods. The primary aim was to compare the direct costs of eHealth (cases) relative to standard care (matched controls) for IBD during three years of follow-up. METHODS: The study design was a retrospective, registry-based follow-up study of patients diagnosed with IBD two years prior, and three years subsequent, to their enrolment in eHealth. Cases were matched 1:4 with controls receiving standard care based on diagnosis, gender, biologics (yes/no) and age (+/- 5 years). RESULTS: We identified 116 cases (76 (66%) with ulcerative colitis (UC) and 40 (34%) with Crohn's disease (CD)) and matched them with 433 controls. IBD-related outpatient costs were only significantly higher for cases in the year of their inclusion in eHealth (€2,949 vs. €1,621 per patient, p =.01). Mean IBD-related admission costs tended to fall after enrolment in eHealth, with mean admission costs per patient at year 3 of follow-up of €74 for cases and €383 for controls (p = .02). Linear extrapolation of the reduction in costs beyond year 3 after enrolment in eHealth revealed that eHealth would be cost neutral or saving, relative to standard care, from year 4. CONCLUSION: IBD-related outpatient costs in both groups were similar and only significantly higher for cases in the year of their enrolment in eHealth, with admission costs typically falling after a patient's inclusion in eHealth. Estimation revealed eHealth to be cost neutral or saving from year 4.

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.

Societal costs attributable to Crohn's disease and ulcerative colitis within the first 5 years after diagnosis: a Danish nationwide cost-of-illness study 2002-2016.

Objective: There is little information on cost-of-illness among patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) in Denmark. The objective of this study was to estimate the average 5-year societal costs attributable to CD or UC patients in Denmark with incidence in 2003-2015, including costs related to health care, prescription medicine, home care and production loss.Materials and methods: A national register-based, cost-of-illness study was conducted using an incidence-based approach to estimate societal costs. Incident patients with CD or UC were identified in the National Patient Registry and matched with a non-IBD control from the general population on age and sex. Attributable costs were estimated applying a difference-in-difference approach, where the total costs among individuals in the control group were subtracted from the total costs among patients.Results: CD and UC incidence fluctuated but was approximately 14 and 31 per 100,000 person years, respectively. The average attributable costs were highest the first year after diagnosis, with costs equalling €12,919 per CD patient and €6,501 per UC patient. Hospital admission accounted for 36% in the CD population and 31% in the UC population, the first year after diagnosis. Production loss exceeded all other costs the third-year after diagnosis (CD population: 52%; UC population: 83%).Conclusions: We found that the societal costs attributable to incident CD and UC patients are substantial compared with the general population, primarily consisting of hospital admission costs and production loss. Appropriate treatment at the right time may be beneficial from a societal perspective.

Cost Burden of Crohn's Disease and Ulcerative Colitis in the 10-Year Period Before Diagnosis-A Danish Register-Based Study From 2003-2015.

BACKGROUND: The diagnostic delay in inflammatory bowel disease (IBD) is well known, yet the costs associated with diagnoses before IBD diagnosis have not yet been reported. This study explored societal costs and disease diagnoses 10 years before Crohn's disease (CD) and ulcerative colitis (UC) diagnosis in Denmark. METHODS: This national register study included patients diagnosed between 2003 and 2015 identified in the Danish National Patient Registry (NPR) and controls who were individually matched on age and sex from the general population. Societal costs included health care services, prescription medicine, home care services, and labor productivity loss. Prediagnostic hospital contact occurring before CD or UC diagnosis was identified using the NPR. Average annual costs per individual were calculated before the patient's first CD or UC diagnosis. A 1-sample t test was then applied to determine significance in differences between cases and controls. RESULTS: Among CD (n = 9019) and UC patients (n = 20,913) the average societal costs were higher throughout the entire 10-year period before the diagnosis date compared with the general population. The difference increased over time and equaled €404 for CD patients and €516 for UC patients 10 years before diagnosis and €3377 and €2960, respectively, in the year before diagnosis. Crohn's disease and UC patients had significantly more diagnoses before their CD and UC diagnosis compared with the general population. CONCLUSIONS: Compared with the general population, the societal costs and number of additional diagnoses among CD and UC patients were substantially higher in the 10-year period before diagnosis.

Using eHealth strategies in delivering dietary and other therapies in patients with irritable bowel syndrome and inflammatory bowel disease.

Health-care systems around the world are facing increasing costs. Non-adherent, chronically ill patients are one such expense incurred by health-care providers. Web-based home-monitoring of patients-or eHealth-has been shown to increase adherence to medical therapy, facilitate contact between patients and health-care professionals, and reduce time to remission for patients with inflammatory bowel disease (IBD). Web-based treatment is a supportive tool for the health-care provider in an out-patient clinic. eHealth web-programs, such as the Constant Care application, visualize disease activity in a traffic light system and empower patients to screen for disease activity, enabling them to respond appropriately to their symptoms. The eHealth screening procedure for monitoring both pediatric and adult IBD patients is based on a self-obtained symptom score, together with a fecal biomarker for inflammation (fecal calprotectin) that the patients can measure independently using their smart phone, providing both patient and physician with an immediate disease status that they can react to instantaneously. Likewise, web applications for IBD patients, web applications for irritable bowel syndrome (IBS) patients and also IBD patients with co-existing IBS, have proven valuable for monitoring and treating IBS symptoms with a diet low in fermentable oligo-, di-, monosaccharides and polyols (low-FODMAP diet). With careful disease monitoring via the web application and increased patient adherence, eHealth might be capable of improving the natural disease course of IBD and IBS.

Construction and validation of a web-based epidemiological database for inflammatory bowel diseases in Europe An EpiCom study.

BACKGROUND: The EpiCom-study investigates a possible East-West-gradient in Europe in the incidence of IBD and the association with environmental factors. A secured web-based database is used to facilitate and centralize data registration. AIM: To construct and validate a web-based inception cohort database available in both English and Russian language. METHOD: The EpiCom database has been constructed in collaboration with all 34 participating centers. The database was translated into Russian using forward translation, patient questionnaires were translated by simplified forward-backward translation. Data insertion implies fulfillment of international diagnostic criteria, disease activity, medical therapy, quality of life, work productivity and activity impairment, outcome of pregnancy, surgery, cancer and death. Data is secured by the WinLog3 System, developed in cooperation with the Danish Data Protection Agency. Validation of the database has been performed in two consecutive rounds, each followed by corrections in accordance with comments. RESULTS: The EpiCom database fulfills the requirements of the participating countries' local data security agencies by being stored at a single location. The database was found overall to be "good" or "very good" by 81% of the participants after the second validation round and the general applicability of the database was evaluated as "good" or "very good" by 77%. In the inclusion period January 1st -December 31st 2010 1336 IBD patients have been included in the database. CONCLUSION: A user-friendly, tailor-made and secure web-based inception cohort database has been successfully constructed, facilitating remote data input. The incidence of IBD in 23 European countries can be found at www.epicom-ecco.eu.

E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided 'Constant-care' approach.

BACKGROUND: The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities' focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients' education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial 'Constant-care' was undertaken in Denmark and Ireland. METHODS: 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. RESULTS: 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group. CONCLUSION: The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.

Best practice in the management of mild-to-moderately active ulcerative colitis and achieving maintenance of remission using mesalazine.

Optimizing treatment goals in ulcerative colitis requires recognizing the needs of patients. It is increasingly recognized that adapting treatment strategies aligned with patient needs can improve patient compliance and consequently minimize relapse rates. Tailoring of treatment strategies can improve not only patient quality of life, and decrease the number harmed by adverse events from more potent drugs, but can also save valuable healthcare costs by avoiding high-cost treatment interventions associated with acute ulcerative colitis. This review will consider several elements of mesalazine management from the patient perspective based on a range of clinical and patient-focused evidence. By highlighting patient preferences in disease management it is envisaged that this review will aid physicians to optimize treatment decisions with the different mesalazine preparations available.

A maximum likelihood estimator of a Markov model for disease activity in Crohn's disease and ulcerative colitis for annually aggregated partial observations.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases that have a remitting, relapsing nature. During relapse, they are treated with drugs and surgery. The present study was based on individual data from patients diagnosed with CD or UC at Herlev University Hospital, Copenhagen, Denmark, during 1991 to 1993. The data were aggregated over calendar years; for each year, the number of relapses and the number of surgical operations were recorded. Our aim was to estimate Markov models for disease activity in CD and UC, in terms of relapse and remission, with a cycle length of 1 month. The purpose of these models was to enable evaluation of interventions that would shorten relapses or postpone future relapses. An exact maximum likelihood estimator was developed that disaggregates the yearly observations into monthly transition probabilities between remission and relapse. These probabilities were allowed to be dependent on the time since start of relapse and on the time since start of remission, respectively. The estimator, initially slow, was successfully optimized to shorten the execution time. The estimated disease activity model for CD fits well to observed data and has good face validity. The disease activity model is less suitable for UC due to its transient nature through the presence of curative surgery.

Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease.

BACKGROUND: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.

Effect of phenotype on health care costs in Crohn's disease: A European study using the Montreal classification.

BACKGROUND: Crohn's disease (CD) is a chronic inflammation of the gastrointestinal tract associated with life-long high health care costs. We aimed to determine the effect of disease phenotype on cost. METHODS: Clinical and economic data of a community-based CD cohort with 10-year follow-up were analyzed retrospectively in relation to Montreal classification phenotypes. RESULTS: In 418 patients, mean total costs of health care for the behavior phenotypes were: nonstricturing-nonpenetrating 1690, stricturing 2081, penetrating 3133 and penetrating-with-perianal-fistula 3356 €/patient-phenotype-year (P<0.001), and mean costs of surgical hospitalization 215, 751, 1293 and 1275 €/patient-phenotype-year respectively (P<0.001). Penetrating-with-perianal-fistula patients incurred significantly greater expenses than penetrating patients for total care, diagnosis and drugs, but not surgical hospitalization. Total costs were similar in the location phenotypes: ileum 1893, colon 1748, ileo-colonic 2010 and upper gastrointestinal tract 1758 €/patient-phenotype-year, but surgical hospitalization costs differed significantly, 558, 209, 492 and 542 €/patient-phenotype-year respectively (P<0.001). By multivariate analysis, the behavior phenotype significantly impacted total, medical and surgical hospitalization costs, whereas the location phenotype affected only surgical costs. Younger age at diagnosis predicted greater surgical expenses. CONCLUSIONS: Behavior is the dominant phenotype driving health care cost. Use of the Montreal classification permits detection of cost differences caused by perianal fistula.

Cost analysis and cost determinants in a European inflammatory bowel disease inception cohort with 10 years of follow-up evaluation.

BACKGROUND & AIMS: Economic analysis in chronic diseases is a prerequisite for planning a proper distribution of health care resources. We aimed to determine the cost of inflammatory bowel disease, a lifetime illness with considerable morbidity. METHODS: We studied 1321 patients from an inception cohort in 8 European countries and Israel over 10 years. Data on consumption of resources were obtained retrospectively. The cost of health care was calculated from the use of resources and their median prices. Data were analyzed using regression models based on the generalized estimating equations approach. RESULTS: The mean annual total expenditure on health care was 1871 Euro/patient-year for inflammatory bowel disease, 1524 Euro/patient-year for ulcerative colitis, and 2548 Euro/patient-year for Crohn's disease (P < .001). The most expensive resources were medical and surgical hospitalizations, together accounting for 63% of the cost in Crohn's disease and 45% in ulcerative colitis. Total and hospitalization costs were much higher in the first year after diagnosis than in subsequent years. Differences in medical and surgical hospitalizations were the primary cause of substantial intercountry variations of cost; the mean cost of health care was 3705 Euro/patient-year in Denmark and 888 Euro/patient-year in Norway. The outlay for mesalamine, a costly medication with extensive use, was greater than for all other drugs combined. Patient age at diagnosis and sex did not affect costs. CONCLUSIONS: In this multinational, population-based, time-dependent characterization of the health care cost of inflammatory bowel disease, increased expenditure was driven largely by country, diagnosis, hospitalization, and follow-up year.

Disease outcome of inflammatory bowel disease patients: general outline of a Europe-wide population-based 10-year clinical follow-up study.

OBJECTIVE: To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors. MATERIALS AND METHODS: A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization. RESULTS: Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries. CONCLUSIONS: This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.

The role of quality of care in health-related quality of life in patients with IBD.

In the literature there are indications of associations between health-related quality of life (HRQoL) in inflammatory bowel disease and disease activity, psychological status, coping, stressful life events, and social support. The aim of this study was to examine whether a relation exists between quality of health care and HRQoL, taking possible confounding variables into account. For this purpose, one single questionnaire was compiled from existing validated questionnaires. A population-based inception cohort of 1056 patients with inflammatory bowel disease in eight countries, diagnosed 6 to 8 years prior to the study, was approached to participate. In total, 824 patients responded (78%), and 517 could be included in statistical analyses. It was shown that in inflammatory bowel disease HRQoL was indeed influenced by quality of care (particularly with regard to the parameters of "providing information," "costs," and "courtesy"), as well as by disease activity, psychological status, type of hospital, social support, stressful life events, and way of administration of the questionnaire. Patients with active disease had lower psychological status and HRQoL scores at the time of the survey than patients without active disease. However, quality of care scores did not differ between these groups. The care aspect "costs" was scored worse by CD compared with UC patients, probably caused by a potentially more expensive treatment. In conclusion, it is shown in a large exploratory study, for the first time, that in inflammatory bowel disease, quality of care has a significant role in determining health-related quality of life.