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-TNFrelated healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

OBJECTIVE: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes. DESIGN: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies. RESULTS: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population. CONCLUSION: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies

Sex Differences in Neoplastic Progression in Barrett's Esophagus:A Multicenter Prospective Cohort Study

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as highgrade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models

Published diagnostic models safely excluded colorectal cancer in an independent primary care validation study

OBJECTIVE: To validate published diagnostic models for their ability to safely reduce unnecessary endoscopy referrals in primary care patients suspected of significant colorectal disease. STUDY DESIGN AND SETTING: Following a systematic literature search, we independently validated the identified diagnostic models in a cross-sectional study of 810 Dutch primary care patients with persistent lower abdominal complaints referred for endoscopy. We estimated diagnostic accuracy measures for colorectal cancer (N=37) and significant colorectal disease (N=141; including colorectal cancer, inflammatory bowel disease, diverticulitis, or >1cm adenomas). RESULTS: We evaluated 18 models - 12 specific for colorectal cancer -, of which most were able to safely rule out colorectal cancer: the best model (NICE-1) prevented 59% of referrals (95% confidence interval (CI): 56-63%), with 96% sensitivity (95%CI: 83-100%), 100% negative predictive value (NPV; 95%CI: 99-100%), and an area under the receiver operating characteristics curve (AUC) of 0.86 (95%CI: 0.80-0.92). The models performed less for significant colorectal disease: the best model (Brazer) prevented 23% of referrals (95%CI: 20-26%), with 95% sensitivity (95%CI: 90-98%), 96% NPV (95%CI: 92-98%), and an AUC of 0.73 (95%CI: 0.69-0.78). CONCLUSION: Most models safely excluded colorectal cancer in many primary care patients with lower gastrointestinal complaints referred for endoscopy. Models performed less well for significant colorectal disease

Control Crohn Safe with episodic adalimumab monotherapy as first-line treatment study (CoCroS): study protocol for a randomised controlled trial

Introduction Crohn’s disease (CD) is a chronic inflammatory bowel disease with a heterogeneous clinical presentation, relapse rate and treatment response. At present, no markers are available to adequately predict disease course at diagnosis. To prevent overtreatment of patients with a relative mild disease course, a step-up approach starting with corticosteroids is usually applied. Timely introduction of potentially disease modifying drugs and tight control of mucosal inflammation are crucial to prevent disease-related complications in patients with a complex disease course. We hypothesise that episodic treatment with adalimumab monotherapy in combination with close monitoring after drug discontinuation improves long-term outcome and reduces drug-related side effects, while preventing overtreatment.Methods and analysis In this pragmatic multicentre randomised controlled trial, newly diagnosed CD patients or CD patients with a flare, naïve to thiopurines and biologicals, will be included and randomised 1:1 to open-label episodic (ie, 24 weeks) adalimumab monotherapy or step-up care starting with corticosteroids. The primary outcome is the number of yearly quarters of corticosteroid free clinical (Monitor Inflammatory Bowel Disease At Home score ≤3) and biochemical (C reactive protein within normal range and faecal calprotectin ≤200 µg/g) remission at week 96. Secondary outcomes are total healthcare costs, cumulative corticosteroid dose, proportion of patients with endoscopic remission at week 24, corticosteroid-free clinical remission, time to remission and patient-reported outcome measures on quality of life, (work) disability and treatment adherence. Safety outcomes are drug-related and disease-related adverse events and disease progression on MRI-enterography at week 96.Ethics and dissemination This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 21 August 2019 (METC18-076) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.Trial registration number NCT03917303

Published diagnostic models safely excluded colorectal cancer in an independent primary care validation study

OBJECTIVE: To validate published diagnostic models for their ability to safely reduce unnecessary endoscopy referrals in primary care patients suspected of significant colorectal disease. STUDY DESIGN AND SETTING: Following a systematic literature search, we independently validated the identified diagnostic models in a cross-sectional study of 810 Dutch primary care patients with persistent lower abdominal complaints referred for endoscopy. We estimated diagnostic accuracy measures for colorectal cancer (N=37) and significant colorectal disease (N=141; including colorectal cancer, inflammatory bowel disease, diverticulitis, or >1cm adenomas). RESULTS: We evaluated 18 models - 12 specific for colorectal cancer -, of which most were able to safely rule out colorectal cancer: the best model (NICE-1) prevented 59% of referrals (95% confidence interval (CI): 56-63%), with 96% sensitivity (95%CI: 83-100%), 100% negative predictive value (NPV; 95%CI: 99-100%), and an area under the receiver operating characteristics curve (AUC) of 0.86 (95%CI: 0.80-0.92). The models performed less for significant colorectal disease: the best model (Brazer) prevented 23% of referrals (95%CI: 20-26%), with 95% sensitivity (95%CI: 90-98%), 96% NPV (95%CI: 92-98%), and an AUC of 0.73 (95%CI: 0.69-0.78). CONCLUSION: Most models safely excluded colorectal cancer in many primary care patients with lower gastrointestinal complaints referred for endoscopy. Models performed less well for significant colorectal disease

Cost-effectiveness of Telemedicine-directed Specialized vs Standard Care for Patients With Inflammatory Bowel Diseases in a Randomized Trial

BACKGROUND & AIMS: Telemedicine can be used to monitor determinants and outcomes of patients with chronic diseases, possibly increasing the quality and value of care. Telemedicine was found to reduce outpatient visits and hospital admissions for patients with inflammatory bowel diseases (IBD). We performed a full economic evaluation of telemedicine interventions in patients with IBD, comparing the cost-utility of telemedicine vs standard care. METHODS: We performed a randomized trial of 909 patients with IBD at 2 academic and 2 non-academic hospitals in The Netherlands. Patients were randomly assigned to groups that received telemedicine (myIBDcoach; n = 465) or standard outpatient care (n = 444) and followed for 12 months. Costs were measured from a societal perspective. Direct healthcare costs were based on actual resource use. Indirect costs comprised self-reported hours sick leave from work, intervention costs (annual license fee of (sic)40 per patient [$45]), and utility costs (assessed using EQ5D). Cost-utility and uncertainty were estimated using the non-parametric bootstrapping method. RESULTS: Telemedicine resulted in lower mean annual costs of (sic)547/patient [$612] (95% CI, (sic)1029-2143 [$1150-2393]; mean costs of (sic)9481 [$10,587] for standard care and (sic)8924 [$9965] for telemedicine) without changing quality adjusted life years. At the Dutch threshold of (sic)80,000 [$89,335] per quality adjusted life year, the intervention had increased incremental cost-effectiveness over standard care in 83% of replications and an incremental net monetary benefit of (sic)707/patient [$790] (95$1386-2841]). CONCLUSIONS: Telemedicine with myIBDcoach is cost saving and has a high probability of being cost effective for patients with IBD. This self-management tool enables continuous registration of quality indicators and (patient-reported) outcomes and might help reorganize IBD care toward value-based healthcare