Mariëlle Romberg-Camps

Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study.

Objective The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. Design Crohns disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. Results A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. Conclusions We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

OBJECTIVES:Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group.METHODS:IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and “surgical” and “nonsurgical” recurrence rates were calculated as outcome parameters.RESULTS:In total, 476 Crohns disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective.CONCLUSIONS:This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort.

Background: The importance of fatigue in chronic disease has been increasingly recognized; however, little is known about fatigue in inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and severity of fatigue and the impact on health‐related quality of life (HRQoL) in patients included in a population‐based IBD cohort in the Netherlands. Methods: IBD patients, diagnosed between January 1st, 1991, and January 1st, 2003, were followed up for a median of 7.1 years. They completed a questionnaire, which included a disease activity score, the Multidimensional Fatigue Inventory (MFI‐20), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Short Form health survey (SF‐36). Hemoglobin levels were recorded. Results: Data were available in 304 Crohns disease (CD), 368 ulcerative colitis (UC), and 35 indeterminate colitis (IC) patients. During quiescent disease, the prevalence of fatigue was nearly 40%. MFI‐20 and HRQoL scores were significantly worse in IBD patients having active disease. In a multivariate analysis, disease activity was positively related with the level of fatigue in both CD and UC. In UC, anemia influenced the general fatigue score independently of disease activity. Disease activity as well as fatigue were independently associated with an impaired IBDQ. Conclusions: In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL. (Inflamm Bowel Dis 2010)

Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991–2002: Incidence, diagnostic delay, and seasonal variations in onset of symptoms

BACKGROUND AND AIMS Increasing incidence in Inflammatory Bowel Disease (IBD) has been suggested. Recent data on population based incidence rates within Europe are however scarce. Primary aim was to investigate prospectively the incidence of IBD within a well-defined geographical and administrative area of the Netherlands, the South Limburg IBD registry. Secondary aims were to study the duration of symptoms before diagnosis (lag time) and seasonal influences on the incidence of IBD. METHODS The incidence was examined using standardized registration of all newly diagnosed IBD patients, between 1-1-1991 and 1-1-2003. Medical records were reviewed to verify the diagnosis. At inclusion, diagnostic lag time was registered in months. RESULTS Age standardized incidence rates per 100,000 person-years (p-y) were: Crohns Disease, male 4.84, female 7.58; Ulcerative Colitis, male 8.51, female 6.92; and Indeterminate Colitis, male 1.05, female 0.93. Incidence rates did not significantly changes over time in either Crohns Disease, Ulcerative Colitis or Indeterminate Colitis. Lag time was 5 (0-360) months in Crohns Disease, 3.0 (0-480) months in Ulcerative Colitis and 3.0 (0-180) months in Indeterminate Colitis. Lag time was not significantly different between the periods 1991-1993 and 2000-2002, and no statistical differences in the onset of symptoms per calendar month or season were found. CONCLUSIONS Our results, from the South Limburg region (the Netherlands), show no significant change in incidence rates of IBD. The incidence found is relatively high compared to other European countries. Lag time did not change during the study period, and seasonal influence of incidence rates could not be confirmed.

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy

BACKGROUND AND AIMS Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235 pmol/8×10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263 pmol/8×10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235 pmol/8×10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

Background: The aim was to evaluate overall and disease‐specific mortality in a population‐based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. Methods: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. Results: At the censoring date, 72 out of 1187 patients had died (21 Crohns disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7–1.6) for CD, 0.9 (0.7–1.2) for UC and 0.7 (0.2–1.7) for IC. Disease‐specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8–16.4) and UC (SMR 3.4, 95% CI: 1.4–7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2–0.9). Conclusions: In this population‐based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow‐up. Caution in interpreting the finding on mortality risk from cancer is needed as follow‐up was probably to short to observe IBD‐related cancers. (Inflamm Bowel Dis 2010)

Risk factors of work disability in patients with inflammatory bowel disease - A Dutch nationwide web-based survey: Work disability in inflammatory bowel disease.

BACKGROUND Inflammatory bowel disease (IBD) is associated with high costs to society. Few data on the impact of IBD on work disability and potential predictive factors are available. AIM To assess the prevalence of and predictive factors for work disability in Crohns disease (CD) and ulcerative colitis (UC). METHODS A web-based questionnaire was sent out in seven university hospitals and seven general hospitals in the Netherlands. Initially, 3050 adult IBD patients were included in this prospective, nationwide cohort study, whereof 2629 patients were within the working-age (18-64 years). We used the baseline questionnaire to assess the prevalence rates of work disability in CD and UC patients within working-age. Prevalence rates were compared with the Dutch background population using age- and sex-matched data obtained from Statistics Netherlands. Multivariable logistic regression analyses were performed to identify independent demographic- and disease-specific risk factors for work disability. RESULTS In CD, 18.3% of patients was fully disabled and 8.8% partially disabled, compared to 9.5% and 5.4% in UC patients (p<0.01), respectively. Compared to Dutch controls, the prevalence was significantly higher, especially in CD patients. Higher age, low education, depression, chronic back pain, joint manifestations and typical disease-related risk factors such as penetrating disease course and surgery in the past were all found to be associated with work disability. CONCLUSION We report high work disability rates in a large sample of IBD patients in the Netherlands. CD patients suffer more frequently from work disability than UC patients. A combination of demographic and disease-related factors is predictive of work disability.

Evolution of costs of inflammatory bowel disease over two years of follow-up

Background With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings In total 1,307 Crohns disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02–3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61–13.86)). Conclusions BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Telemedicine for management of inflammatory bowel disease (myIBDcoach): a pragmatic, multicentre, randomised controlled trial

BACKGROUND Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care. METHODS We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1:1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02173002. FINDINGS Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1·55 [SD 1·50]) than in the standard care group (2·34 [1·64]; difference -0·79 [95% CI -0·98 to -0·59]; p<0·0001), as was the mean number of hospital admissions (0·05 [0·28] vs 0·10 [0·43]; difference -0·05 [-0·10 to 0·00]; p=0·046). At 12 months, both groups reported high mean patient-reported quality of care scores (8·16 [1·37] in the telemedicine group vs 8·27 [1·28] in the standard care group; difference 0·10 [-0·13 to 0·32]; p=0·411). The mean numbers of flares, corticosteroid courses, emergency visits, and surgeries did not differ between groups. INTERPRETATION Telemedicine was safe and reduced outpatient visits and hospital admissions compared with standard care. This self-management tool might be useful for reorganising care of inflammatory bowel disease towards personalised and value-based health care. FUNDING Maastricht University Medical Centre and Ferring.

Disease Outcome of Ulcerative Colitis in an Era of Changing Treatment Strategies: Results from the Dutch Population-based IBDSL Cohort

BACKGROUND AND AIMS In the past decades, treatment options and strategies for ulcerative colitis [UC] have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the past two decades in the South-Limburg area of The Netherlands. METHODS In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 [cohort A], cohort 1998-2005 [cohort B], and cohort 2006-2010 [cohort C]. The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios [HR] for early colectomy [within 6 months after diagnosis], late colectomy [beyond 6 months after diagnosis], and hospitalisation were calculated using Cox regression models. RESULTS In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators [8.1%, 22.8% and 21.7%, respectively, p < 0.01] and biological agents [0%, 4.3% and 10.6%, respectively, p < 0.01] was observed. The early colectomy rate decreased from 1.5% in cohort A to 0.5% in cohort B [HR 0.14; 95% confidence interval 0.04-0.47], with no further decrease in cohort C [0.3%, HR 0.98; 95% confidence interval 0.20-4.85]. Late colectomy rate remained unchanged over time [4.0% vs 5.2% vs 3.6%, respectively, p = 0.54]. Hospitalisation rate was also similar among cohorts [22.3% vs 19.5% vs 18.3%, respectively, p = 0.10]. CONCLUSION Over the past two decades, a reduction in early colectomy rate was observed, with no further reduction in the most recent era. Late colectomy rate and hospitalisation rate remained unchanged over time.