Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease.

BACKGROUND: Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed. AIM: To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease. METHODS: We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks. RESULTS: We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03-2.35, p = 0.036). CONCLUSIONS: First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease. TRIAL REGISTRATION NUMBER: NCT02517684.

Simultaneous Assessment of Urinary and Fecal Volatile Organic Compound Analysis in De Novo Pediatric IBD.

Endoscopic evaluation is mandatory in establishing the diagnosis of pediatric inflammatory bowel disease (IBD), but unfortunately carries a high burden on patients. Volatile organic compounds (VOC) have been proposed as alternative, noninvasive diagnostic biomarkers for IBD. The current study aimed to assess and compare the potential of fecal and urinary VOC as diagnostic biomarkers for pediatric IBD in an intention-to-diagnose cohort. In this cohort study, patients aged 4-17 years, referred to the outpatient clinic of a tertiary referral center under suspicion of IBD, were eligible to participate. The diagnosis was established by endoscopic and histopathologic assessment, participants who did not meet the criteria of IBD were allocated to the control group. Participants were instructed to concurrently collect a fecal and urinary sample prior to bowel lavage. Samples were analyzed by means of gas chromatography-ion mobility spectrometry. In total, five ulcerative colitis patients, five Crohn's disease patients, and ten age and gender matched controls were included. A significant difference was demonstrated for both fecal (p-value, area under the curve; 0.038, 0.73) and urinary (0.028, 0.78) VOC profiles between IBD and controls. Analysis of both fecal and urinary VOC behold equal potential as noninvasive biomarkers for pediatric IBD diagnosis.

Faecal gas analysis by electronic nose as novel, non-invasive method for assessment of active and quiescent paediatric inflammatory bowel disease: Proof of principle study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) and its two phenotypes ulcerative colitis (UC) and Crohn's disease (CD) are essentially assessed by endoscopy, both in initial diagnostic work-up and during follow-up. This carries a high burden, especially on paediatric patients. Faecal volatile organic compounds (VOCs) are considered potential non-invasive biomarkers for intestinal diseases linked to gut microbiota alterations. We hypothesized that faecal VOC analysis by electronic nose allows discrimination of children with CD, UC and controls during active disease and remission. METHODS: Faecal VOC patterns of children with newly diagnosed IBD and controls were studied by an electronic nose (Cyranose 320®), at baseline and upon achieving remission at 6-weeks of follow-up. Disease activity was assessed by global physician's assessment, substantiated by serum C-reactive protein and faecal calprotectin. Internally cross-validated receiver-operator-characteristic curves and corresponding sensitivity and specificity for detection of IBD were calculated RESULTS: Faecal VOC profiles of patients with UC (26) and CD (29) differed from controls (28); in active disease (AUC±95% CI, p-value, sensitivity, specificity: 1.00±0.00; p<0.001, 100%, 100%) and (0.85±0.05, p<0.001, 86%, 67%) and in clinical remission (0.94±0.06, p<0.001, 94%, 94%) and (0.94±0.06, p<0.001, 94%, 94%), respectively. Furthermore, CD-patients differed from UC-patients during active disease (0.96±0.03; p<0.001, 97%, 92%), and upon achieving clinical remission (0.81±0.08, p=0.002, 88%, 72%). CONCLUSION: Faecal VOC analysis allowed discrimination of paediatric patients with IBD from controls, both during active disease and remission. It therefore has potential as non-invasive test, in both diagnostic work-up and assessment of disease activity in IBD.

Empty colon: a pitfall in the assessment of colonic transit time.

We report a misleading outcome of colonic transit time (CTT) assessment in an adolescent girl with functional constipation. We found prolonged total and right segmental CTT despite high doses of oral polyethylene glycol 4000 and repeated treatment with polyethylene glycol-electrolyte solution (Klean-Prep®) by nasogastric tube. A colonoscopy aiming at disimpaction of a possible faecal mass revealed an empty colon with dozens of radio-opaque markers adhered to the colonic wall. This report shows that the result of a CTT cannot be accepted blindly. Especially the clustering of many markers within narrow margins might point at entrapment of markers in mucus against the colonic wall.