Variation Between Hospitals in Outcomes and Costs of IBD Care: Results From the IBD Value Study.

BACKGROUND: Data on variation in outcomes and costs of the treatment of inflammatory bowel disease (IBD) can be used to identify areas for cost and quality improvement. It can also help healthcare providers learn from each other and strive for equity in care. We aimed to assess the variation in outcomes and costs of IBD care between hospitals. METHODS: We conducted a 12-month cohort study in 8 hospitals in the Netherlands. Patients with IBD who were treated with biologics and new small molecules were included. The percentage of variation in outcomes (following the International Consortium for Health Outcomes Measurement standard set) and costs attributable to the treating hospital were analyzed with intraclass correlation coefficients (ICCs) from case mix-adjusted (generalized) linear mixed models. RESULTS: We included 1010 patients (median age 45 years, 55% female). Clinicians reported high remission rates (83%), while patient-reported rates were lower (40%). During the 12-month follow-up, 5.2% of patients used prednisolone for more than 3 months. Hospital costs (outpatient, inpatient, and medication costs) were substantial (median: €8323 per 6 months), mainly attributed to advanced therapies (€6611). Most of the variation in outcomes and costs among patients could not be attributed to the treating hospitals, with ICCs typically between 0% and 2%. Instead, patient-level characteristics, often with ICCs above 50%, accounted for these variations. CONCLUSIONS: Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of care. Future quality improvement initiatives should look at differences in structure and process measures of care and implement patient-level interventions to improve quality of IBD care. TRIAL REGISTRATION NUMBER: NL8276.

Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of inflammatory bowel disease care. Future quality improvement initiatives should look at differences in structure and process measures and implement patient-level interventions to improve quality of inflammatory bowel disease care.

Cost-Effectiveness Analysis of Increased Adalimumab Dose Intervals in Crohn's Disease Patients in Stable Remission: The Randomized Controlled LADI Trial.

BACKGROUND AND AIMS: We aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn's disease [CD] in stable clinical and biochemical remission. DESIGN: We conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels. RESULTS: We randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: -0.017, 95% confidence interval [-0.044; 0.004]) and total costs (-€943, [-€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (-€2545, [-€2780; -€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost-utility analysis showed that the iNMB was €594 [-€2099; €2050], €69 [-€2908; €1965] and -€455 [-€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective. CONCLUSION: When the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: epidemiology, pathogenesis and clinical management.

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.

Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents.

BACKGROUND: Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. AIM: To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. METHODS: A systematic review of all population-based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. RESULTS: Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia $4417 (range $1230-$31 161); Europe $12 439 ($7694-$15 807) and North America $17 495 ($14 454-$20 535). For ulcerative colitis (UC), these were $1606 ($309-$14 572), $7224 ($3228-$9779) and $13 559 ($13 559-$13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) $5638 ($5638-$5638) and $4828 ($4828-$4828); Europe $2660 ($641-$5277) and $2394 ($651-$5992); North America $752 ($307-$1303) and $1443 ($85-$2350). CONCLUSION: IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined.

Fatigue in IBD: epidemiology, pathophysiology and management.

Fatigue is an important clinical problem in patients with IBD, affecting nearly 50% of patients in clinical remission and > 80% of those with active disease. The resulting decrease in quality of life and impaired work productivity and functioning contribute markedly to the societal costs of fatigue. However, despite the burden and effects of fatigue, little is known about its aetiology and pathophysiology, which impairs our ability to effectively treat this symptom. Here, we review the theories behind the development of fatigue in IBD and the role of contributing factors, including nutritional deficiency, inflammation and altered metabolism. We also explore the potential role of the gut microbiome in mediating fatigue and other psychological symptoms through the gut-brain axis. We discuss the efficacy of nutrient repletion and various psychological and pharmacological interventions on relieving fatigue in patients with IBD and expand the discussion to non-IBD-related fatigue when evidence exists. Finally, we present a therapeutic strategy for the management of fatigue in IBD and call for further mechanistic and clinical research into this poorly studied symptom.

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 Crohn's 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.

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.

Effect of aging on healthcare costs of inflammatory bowel disease: a glimpse into the future.

BACKGROUND: Population aging is expected to result in a substantial additional burden on healthcare resources in the near future. We aimed to assess the current and future impact of aging on direct healthcare costs (DHC) attributed to inflammatory bowel disease (IBD). METHODS: Patients with IBD from a Dutch multicenter cohort filled out 3-monthly questionnaires for 2 years. Elderly (≥60 yr) and younger patients (18-60 yr) IBD were analyzed for differences in 3-monthly DHC, productivity losses, and out-of-pocket costs. Prevalence rates were obtained from a health insurance database. Estimates of annual DHC and prevalence rates were applied to the total Dutch adult population in 2011 and then projected to 2040, using predicted changes in population demography, prices, and volume. RESULTS: IBD-attributable DHC were lower in elderly than in younger patients with IBD with respect to 3-monthly DHC (&OV0556;359 versus &OV0556;978, P < 0.01), productivity losses (&OV0556;108 versus &OV0556;456, P < 0.01), and out-of-pocket costs (&OV0556;40 versus &OV0556;57, P < 0.01). Between 2011 and 2040, the percentage of elderly IBD patients in the Netherlands has been projected to rise from 24% to 35%. Between 2011 and 2040, DHC of the total IBD population in the Netherlands are projected to increase from &OV0556;161 to &OV0556;661 million. Population aging accounted for 1% of this increase, next to rising prices (29%), and volume growth (70%). CONCLUSIONS: Population aging has a negligible effect on IBD-attributable DHC of the IBD population in the near future, because the average costs incurred by elderly patients with IBD are considerably lower than those incurred by younger patients with IBD.

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: Crohn's 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.

Solution focused therapy: a promising new tool in the management of fatigue in Crohn's disease patients psychological interventions for the management of fatigue in Crohn's disease.

BACKGROUND: Crohn's disease patients have a decreased Quality of Life (QoL) which is in part due to extreme fatigue. In a pilot study we prospectively assessed the feasibility and effect of psychological interventions in the management of fatigue. METHODS: Patients with quiescent Crohn's disease and a high fatigue score according to the Checklist Individual Strength were randomized to Problem Solving Therapy (PST), Solution Focused Therapy (SFT) or to a control group (treatment as usual, TAU). Patients completed the Inflammatory Bowel Disease Questionnaire, the EuroQol-5D, and the Trimbos questionnaire for Costs. RESULTS: Twenty-nine patients were included (12 TAU, 9 PST, 8 SFT), of these 72% were female, mean age was 31 years (range 20-50). The SFT group improved on the fatigue scale in 85.7% of the patients, in the PST group 60% showed improved fatigue scores and in the TAU group 45.5%. Although not significant, in both intervention groups the QoL increased. Medical costs lowered in 57.1% of the patients in the SFT group, in the TAU 45.5% and the in PST group 20%. The drop out rate was highest in the PST group (44%; SFT 12.5%; TAU 8.3%). CONCLUSIONS: PST and SFT both positively affect the fatigue and QoL scores in patients with Crohn's disease. SFT seems most feasible with fewer dropouts and is therefore a promising new tool in the management of fatigue in Crohn's disease patients.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).

BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.