Background and Aims Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. Approach and Results We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty‐four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention‐to‐treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma‐glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5‐year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. Conclusions We presented the largest‐ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end‐stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo‐controlled treatment trials are needed to identify effective treatments for pediatric PSC.

Background & AimsWe aim to provide guidance for medical treatment of luminal Crohn’s disease in children.MethodsWe performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn’s disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them.ResultsThe consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation.ConclusionsEvidence-based medical treatment of Crohn’s disease in children is recommended, with thorough ongoing assessments to define treatment success.

Background and Aims Although venous thromboembolism (VTE) is a well-known complication of inflammatory bowel disease (IBD) in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD. Methods We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children diagnosed with IBD <16 years were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario, and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within five years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios (IRR) with 95% confidence intervals (CI). Hazard ratios (HR) from Cox proportional hazards models were pooled with fixed-effects meta-analysis. Results The five-year incidence of VTE among 3593 children with IBD was 31.2 (95%CI 23.7-41.0) per 10,000 person-years (PY) compared to 0.8 (95%CI 0.4-1.7) per 10,000 PY among 16,289 children without IBD (unadjusted IRR 38.84, 95%CI 16.59-90.83; adjusted HR 22.91, 95%CI 11.50-45.63). VTE was less common in Crohn’s disease than ulcerative colitis (unadjusted IRR 0.47, 95%CI 0.27-0.83; adjusted HR 0.52, 95%CI 0.29-0.94). Findings were similar for deep vein thrombosis (DVT) and pulmonary embolism (PE) when comparing children with and without IBD. Conclusions The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature.

Background Marked variation in access to care and health services utilization is a marker of variation in quality of care. With the rising incidence of pediatric inflammatory bowel disease (IBD), we must understand variation in access to and outcomes of care to improve quality. Purpose Describe variation in care for pediatric IBD treated in 4 Canadian provinces. Method Incident cases of IBD diagnosed in children <16y were identified from health administrative data in Alberta (AB), Manitoba, Nova Scotia, and Ontario (ON) using validated algorithms. Children were assigned to one of 8 centres of care using a hierarchical assessment of health services use within 6 months of diagnosis. Children treated by adult gastroenterologists or community-based pediatric gastroenterologists were excluded due to small sample size. Outcomes included IBD-related hospitalizations, emergency department (ED) visits (AB/ON only), and IBD-related abdominal surgery. Hospitalizations and ED visits were counted cumulatively from 6-60 months after diagnosis. The risk of first surgery was defined during the same 6-60 month period. Mixed-effects meta-analysis was used to pool results across centres. Heterogeneity among centres was quantified using I2 (variation in pooled event rates between centres) and τ (standard deviation of the true event rates). R2 quantified the residual heterogeneity in outcomes not attributable to among-province variation. Result(s) We identified 3777 incident cases of pediatric IBD, 2936 (78%) of which were treated at 8 pediatric centres. The number of hospitalizations was 0.67 (95% CI 0.56-0.79) per person with high between-centre heterogeneity (I2 84%, τ 0.1556). Provincial differences accounted for 93% of heterogeneity across centres (residual heterogeneity: I2 29%, τ 0.0412). Hospitalizations were less frequent in AB than other provinces (0.43 vs. 0.72-0.78). Children averaged 1.94 IBD-related ED visits, with significant heterogeneity (I2 99%, τ 1.33) with 99.7% of heterogeneity attributable to among-province differences (residual heterogeneity: I2 32%; τ 0.074). Mean ED visits were 1.1 visits in ON (I2 39%) and 3.7 in AB (I2 0%). Intestinal resection was required by 12% (95% CI 0.08-0.15) of Crohn’s patients with high among-centre heterogeneity (I2 81%, τ 0.042), and low (19%) heterogeneity due to provincial differences (residual heterogeneity: I2 76%; τ 0.039). Colectomy was required by 12% (95% CI 10-14) of children with ulcerative colitis (UC) with no between-centre heterogeneity (I2 0%, τ 0). Conclusion(s) There is a high degree of between-province (but not between-centre, within province) variability in health services utilization among children with IBD. There was significant between-centre variability in surgery rates for Crohn’s, but not colectomy for UC. Differences in patient characteristics or provincial health systems may be more important predictors of variation in care. Surgery for Crohn’s disease may be a target for inter-centre quality improvement efforts. Please acknowledge all funding agencies by checking the applicable boxes below CCC Disclosure of Interest None Declared

Background: Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis.Methods: We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8.Results: Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 μg/mL (interquartile range: 26.5–52.1 μg/mL) pre-dose #2 and 22.5 μg/mL (interquartile range:15.9–32.3 μg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5–0.9 in predicting week 8 clinical remission; a cut-off of 33.0 μg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 μg/mL, interquartile range (IQR) 8.5–21.8 μg/mL vs. 27.7 μg/mL, IQR 17.2–46.7 μg/mL, p = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, p = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3–7.9 days).Conclusions: Infliximab concentrations ≥33 μg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.