Search

Background: Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD., Methods: Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated., Results: Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001)., Conclusions: This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The genetic contribution to inflammatory bowel disease (IBD) encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterise environmental and epigenetic influences. Recently considerable progress has been made in characterising the adult methylome, in epigenome-wide association studies. We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD,UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform. We derive and validate a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI and ARHGEF3), with specificity and high diagnostic accuracy for paediatric IBD in UK and North American cohorts (AUC 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-MeQTL analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD contrary to previous findings. These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn's disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10-12 weeks' induction therapy. At diagnosis, plasma protein profiles unveiled two UC and three CD clusters with distinct disease courses. UC patients displayed unchanged circulating Tmem, while CD exhibited increased frequencies of gut-homing ex-Th17, known for high IFN-γ production. UC#2 had elevated Th17/neutrophil-pathway-related proteins and severe disease, with higher endoscopic and histological damage and Th17/neutrophil infiltration. Although both UC#1 and UC#2 responded to therapy, UC#2 required earlier immunomodulation. CD#3 had lower plasma protein concentrations, especially IFN-γ pathway proteins, fewer gut-homing ex-Th17 and clinically milder disease, confirmed by intestinal gene expression. CD#1 and CD#2 had comparably high Th1-related immune profiles, but CD#1 exhibited higher concentrations of proteins previously associated with poorer prognosis. Both CD clusters responded to induction therapy, with similar one-year outcomes. This study highlights feasibility of discriminating patient-specific immunotypes in IBD, advancing our understanding of immune pathogenesis, needed for tailored treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.    Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn's disease (CD) reporting abdominal pain and compared with noninflamed control biopsies. Potential pronociceptive mediators were identified based on gene upregulation in IBD biopsy tissue and cognate receptor expression in murine colonic sensory neurons. Pronociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity. RNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts, Agt , which encode the precursor to angiotensin II (Ang II), in samples from UC patients ( P = 3.2 × 10 -8 ). Consistent with the marked expression of the angiotensin AT 1 receptor in colonic sensory neurons, Ang II elicited an increase in intracellular Ca 2+ in capsaicin-sensitive, voltage-gated sodium channel subtype Na V 1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT 1 receptor antagonist valsartan. Findings from our study identify AT 1 receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Rare and severe adverse events can occur in children with inflammatory bowel disease (IBD), and the relationship with disease or drug treatment is often uncertain. We aimed to establish a method of reporting adverse events of interest in children with IBD, allowing for estimates of incidence rates with comparison between different regions, and, if possible, to compare with published data on rates of adverse events in children overall., Methods: For this analysis, we used data from the Paediatric Inflammatory Bowel Disease Network for Safety, Efficacy and Treatment and Quality improvement of care (PIBD-SETQuality) Safety Registry, which collects data on multiple rare and severe adverse events in children younger than 19 years with IBD. Overall, the registry collected data on ten prespecified rare and severe adverse events in children with IBD, as established by a panel of paediatric IBD experts, via reports from paediatric gastroenterologists at participating hospitals between Nov 1, 2016, and March 31, 2023. Reporting physicians, who could only be paediatric gastroenterologists or IBD nurses reporting on behalf of paediatric gastroenterologists, were recruited through invitations sent to both national and international IBD networks and at conferences. Once per month, participating paediatric gastroenterologists received an email with an anonymous and unique link to an online survey asking them to report whether any of ten rare and severe adverse events had occurred in a patient in their paediatric-IBD population in the previous month. Prevalent or retrospective rare and severe adverse events were excluded, as were events occurring in children with an unconfirmed diagnosis of IBD or for whom inflammatory colitis was part of a monogenic immunodeficiency disorder. Duplicates and events that did not meet the definitions and criteria were excluded. Physicians could also report other, non-categorised adverse events if they considered them rare and severe. In case of no response, up to two reminders were sent for each per-month survey. Annual denominator data surveys were sent to obtain the total number of person-years for the estimation of incidence rates, which were calculated via Poisson regression models., Findings: Responses were gathered from 220 paediatric gastroenterologists from 167 centres. 121 centres were in Europe, 23 centres were in North America, 17 centres were in Asia, and six centres were in Oceania. Combined, the total population with paediatric IBD consisted of an estimated 30 193 children with 114 528 person-years of follow-up. 451 adverse events were initially reported. After excluding and reorganising adverse events, 402 were eligible; 261 (65%) were categorised and 141 (35%) were non-categorised. The most frequently reported adverse events were venous-thromboembolic events (n=66), renal failure (n=43), opportunistic infections (n=42), and cancer (n=33). Haemophagocytic lymphohistiocytosis (n=4) and liver failure (n=3) were the least frequently reported adverse events. Incidence rates per 10 000 person-years were 5·50 (95% CI 4·25-6·97) for venous-thromboembolic events, 3·75 (2·74-4·99) for renal failure, 3·67 (2·67-4·89) for opportunistic infection, and 2·88 (2·01-3·98) for cancer. Of 66 venous-thromboembolic events, 31 (47%) involved cerebral venous sinus thrombosis at an incidence rate of 2·71 (95% CI 1·86-3·77)., Interpretation: The PIBD-SETQuality Safety Registry enabled us to identify incidence rates of rare and severe adverse events in children with IBD. Our findings can guide physicians and enhance awareness of the incidence of adverse events in children with IBD that are considered to be rare., Funding: EU Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests LdR receives grants from KiddyGoodPills and Vrienden van Sophia; receives payment and honoraria for lectures from AbbVie; and receives support for attending meetings from the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. NMC receives honoraria for manuscript writing from AbbVie and is involved in industry-sponsored studies for Eli Lilly, AbbVie, Janssen, Takeda, and Pfizer. FMR receives grants from Janssen and AbbVie; receives consulting fees and payment or honoraria for lectures, presentatations, speakers bureaus, writing, or educational events from Shering-Plough, Nestlé, MeadJohnson, Ferring, MSD, MSD France, Johnson & Johnson, Centocor, AbbVie, Nestlé Nutrition Institute, Nestlé Health Science, Danone, Takeda, Celgene, Biogen, Eli Lilly, and Bristol Myers Squibb; and receives support for attending meetings from Nestlé, AbbVie, Nestlé Nutrition Institute, Nestlé Health Science, and Celltrion. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Aims: Treatment guidelines for paediatric Crohn's disease [CD] suggest early use of anti-tumour necrosis factor alpha [anti-TNFα] in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort., Methods: Children with newly diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF [<90 days after diagnosis] and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission [SSFR] without treatment intensification [specified as SSFR*] and sustained steroid-free mild/inactive disease without treatment intensification [specified as SSFMI*]. Penalised logistic regression model-based standardisation was applied to estimate the relative risks [RR] of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients, based on presence of predictors of poor outcome [POPOs] and disease activity at diagnosis., Results: In total, 331 children (median age 13.9 years [IQR 12.2-15.3]) were enrolled, with 135 [41%] receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* [30% vs 14%, p <0.001] and SSFMI* [69% vs 33%, p <0.001], with RRs of 2.95 [95% CI 1.63-5.36] and 4.67 [95% CI 2.46-8.87], respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared with mild/inactive disease at diagnosis (5.50 [95% CI 2.51-12.05] vs 2.91 [95% CI 0.92-9.11]), and those with any POPO compared with no POPO (5.05 [95% CI 2.45-10.43] vs 3.41 [95% CI 0.54-21.7])., Conclusion: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Objectives: The objective of this study was to explore the correlation between paediatric Crohn's disease (CD) characteristics, bone health and growth parameters at diagnosis and follow-up., Methods: Retrospective data was collected for 47 children aged 4-16 who were newly diagnosed with CD between January 2018 and December 2019. Mean follow-up time was 2.5 years., Results: Eleven (24%) children had growth delay at diagnosis, which persisted in 4 (44%) of 9 recorded children at follow-up. Of the 35 children tested, 20 (57%) had inadequate Vitamin D levels (<50 mmol/L) at diagnosis. Thirty-seven (79%) children had a dual-energy X-ray absorptiometry scan at diagnosis, with 20 of them having at least 1 low Z -score. Children with poorer bone mineral density and bone mineral concentration Z -scores for age had a younger age at diagnosis ( p  = .042 and p  = .021), more severe disease ( p  = .04 and p  = .029) and a lower BMI ( p  < .001) at diagnosis. Children diagnosed with CD ≥11 years had a lower-than-expected height velocity ( p  < .0001 and p  < .001). Multivariate regression analysis demonstrated an older age of diagnosis was a significant predictor of a lower height velocity at follow-up., Conclusion: Disease severity and age of diagnosis are important CD-related factors that influence bone health and growth. Vitamin D is an accessible component that if optimised can improve all three factors. Monitoring and optimising each aspect systematically has the potential to enable children to achieve their bone health and growth potentials., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission., Methods: This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018. Eligible patients aged 5-17 years and weighing 18-90 kg were randomised 1:1 to either low (900-2400 mg) or high (1800-4800 mg) oral doses of multimatrix mesalamine once daily, stratified by body weight. Interactive response technology was used for randomisation. The primary efficacy outcome was to estimate the clinical response of multimatrix mesalamine (two doses) in different weight groups. Efficacy and safety analyses were conducted in the safety analysis set (Clinicaltrials.gov: NCT02093663; Study completed)., Findings: Overall, 107 patients were randomised into the DBA (n = 54) or DBM phase (n = 88; directly or after completing the double-blind or OLA phases); the overall safety analysis set included 105 patients. In the DBA phase, the high-dose group (n = 17; 65.4%) achieved a higher clinical response rate than the low-dose (n = 10; 37.0%) group; difference 28.3% (95% CI: 2.5-54.2; p = 0.039), odds ratio (OR) 3.21 (95% CI: 1.04-9.88). In the DBM phase at Week 26, similar proportions of patients maintained clinical response in the low-dose (n = 23; 54.8%) and high-dose (n = 24; 53.3%) groups: OR 0.99 (0.42-2.34); p = 0.981. Overall, 246 treatment-emergent adverse events (TEAEs) were reported in 73 patients (69.5%); 23 TEAEs in 14 patients (13.3%) were considered related to the study drug. No treatment-related deaths were reported., Interpretation: Our findings suggested that the benefit-risk ratio of once-daily multimatrix mesalamine in paediatric patients was favourable and comparable with that reported in adults with mild-to-moderate UC., Funding: Shire Development LLC, a Takeda company., Competing Interests: NMC (into employer’s investigator accounts) received speaker fees, advisory board fees, and research funding from Eli Lilly, Takeda, AbbVie, Shire, Pfizer, Roche, Celgene, and 4D Pharma. BK received a grant from Shire for the study research conducted. JK (into employer’s investigator accounts) received speaker fees, advisory board fees, and research funding from Eli Lilly, Celltrion, and Nestlé. BC was an employee of Takeda at the time the study was conducted. MKT is an employee of Takeda and received no specific funding for this work., (© 2023 The Authors.)

Background: Several studies have proposed models to predict disease outcomes in paediatric ulcerative colitis (UC), notably PROTECT, Schechter and PIBD-ahead, but none has been validated by external cohorts AIM: To explore these models in a prospective multicentre inception cohort METHODS: Children newly diagnosed with UC in 17 centres were followed at disease onset and 3 and 12 months thereafter, as well as at last visit. Outcomes included steroid-free remission (SFR) and acute severe colitis (ASC)., Results: Of the 223 included children, 74 (34%), 97 (43%) and 52 (23%) presented with mild, moderate and severe disease, respectively. SFR rate was 35% at 3 months and 47% at 12 months (62% of those with mild disease at diagnosis vs. 41% in moderate-severe disease; p = 0.01). Thirty-six (16%) children developed ASC during the first month after diagnosis, and 53 (24%) during the first year. The AUC of the PROTECT model for predicting SFR at 3 and 12 months was 0.78 [95% CI 0.65-0.92] and 0.57 [95% CI 0.47-0.66], respectively. The sensitivity/specificity/PPV/NPV of Schechter's criteria to predict sustained SFR at 12 months was 50%/60%/35%/74%. ASC was predicted only by the PUCAI score at diagnosis and at 3 months., Conclusions: The PROTECT model had a good predictive utility for SFR at 3 months, but not at 12 months. The other predictive models did not achieve sufficient accuracy, which was far from that reported in the original studies. This highlights the necessity for external validation of any prediction model prior to its implementation into clinical practice., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background & Aims: The TUMMY-UC is a patient-reported outcome measure for pediatric ulcerative colitis (UC) with an observer-reported outcome version for children aged <8 years. It includes eight items selected by concept elicitation interviews. We aimed to finalize the TUMMY-UC by cognitive interviews (stage 2) and to evaluate the index for its psychometric properties (stage 3)., Methods: The TUMMY-UC items were first finalized during 129 cognitive debriefing interviews. Then, in a prospective, multicenter validation study, 84 children who underwent colonoscopy or provided stool for calprotectin completed the TUMMY-UC and various measures of disease activity. Assessments were repeated after 7 and 21 days for evaluating reliability and responsiveness., Results: During stage 2, the items were formatted with identical structure to ensure conceptual equivalence and weighted based on ranking of importance. In stage 3, the TUMMY-UC total score had excellent reliability in repeated assessments (intraclass correlation coefficient, 0.90; 95% confidence interval, 0.84-0.94). It also had moderate to strong correlations with all constructs of disease activity: r = 0.70 with UC endoscopic index of severity, r = 0.63 with the IMPACT-III questionnaire, r = 0.43 with calprotectin, r = 0.80 with the Pediatric Ulcerative Colitis Activity Index, r = 0.75 with global assessment of disease activity, and r = 0.46 with C-reactive protein (all P < .015). The index had excellent discrimination of disease activity, with a score of <9 defining remission (area under the receiver operating characteristic curve, 0.95; 95% confidence interval, 0.93-0.99). The ΔTUMMY-UC showed high responsiveness and differentiated well between children who experienced changed from those with no change., Conclusions: The TUMMY-UC, constructed from patient-reported outcome and observer-reported outcome versions, is a reliable, valid and responsive index that can be now used in practice and clinical trials., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Despite recent approvals for new drugs to treat adults with Crohn's disease or ulcerative colitis, there are only two approved advanced treatment options [infliximab and adalimumab] for children with inflammatory bowel disease [IBD]. There are many potential new therapies being developed for adult and paediatric IBD. Moreover, regulatory agencies in both the European Union and USA have processes in place to support the early planning and initiation of paediatric studies. Nevertheless, unacceptable delays in approvals for use of drugs in children persist, with an average 7-year gap, or longer, between authorization of new IBD drugs for adults and children., Methods: A 2-day virtual meeting was held during April 14-15, 2021 for multi-stakeholders [clinical academics, patient community, pharmaceutical companies and regulators] to discuss their perspectives on paediatric drug development for IBD., Results: The multi-stakeholder group presented, discussed and proposed actions to achieve expediting the approval of new drugs in development for paediatric IBD., Conclusions: Collaborative action points for all stakeholders are required to make progress and facilitate new drug development for children with IBD., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD., Methods: Enrolled patients [aged 2-17 years] with moderate to severe ulcerative colitis [UC] or Crohn's disease [CD] and body weight ≥10 kg were randomized by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6 and 14. Week 14 assessments included PK, clinical response and exposure-response relationship. Safety and immunogenicity were assessed., Results: Randomized patients weighing ≥30 kg [UC, n = 25; CD, n = 24] and <30 kg [UC, n = 19; CD, n = 21] had a baseline mean [standard deviation] age of 13.5 [2.5] and 7.6 [3.2] years, respectively. In almost all indication and weight groups, area under the concentration curve and average concentration increased ~2-fold from low to high dose; the trough concentration was higher in each high-dose arm compared with the low-dose arms. At Week 14, clinical response occurred in 40.0-69.2% of patients with UC and 33.3-63.6% with CD in both weight groups. Clinical responders with UC generally had higher trough concentration vs non-responders, while this trend was not observed in CD. Fourteen per cent [12/88] of patients had treatment-related adverse events and 6.8% [6/88] had anti-drug antibodies., Conclusions: Vedolizumab exposure increased in an approximate dose-proportional manner. No clear dose-response relationship was observed in this limited cohort. No new safety signals were identified., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Objectives: To evaluate the longitudinal evolution of work productivity loss and activity impairment in caregivers of children with inflammatory bowel disease (IBD). We also evaluated the associations between these impairments, IBD-related factors, and caregivers' health-related quality of life (HRQOL) and estimated the indirect costs related to work absenteeism., Study Design: Since January 2017, children with newly diagnosed IBD were enrolled prospectively in the Pediatric Inflammatory Bowel Disease Network for Safety, Efficacy, Treatment and Quality improvement of care study. The impact of pediatric-onset IBD on caregivers' socioeconomic functioning (work and daily activities) and HRQOL was assessed using the Work Productivity and Activity Impairment for caregivers questionnaire and the European Quality of Life Five Dimension Five Level questionnaire, at diagnosis and 3 and 12 months of age. Generalized estimating equation models were applied to evaluate outcomes longitudinally, adjusted for IBD type, disease activity, and child's age at diagnosis., Results: Up to July 2021, 491 children with IBD were eligible for analysis of caregivers' Work Productivity and Activity Impairment questionnaire. At diagnosis, the mean caregivers' employment rate was 78.4%; the adjusted mean work productivity loss was 44.6% (95% CI, 40.2%-49.0%), and the adjusted mean activity impairment was 34.3% (95% CI, 30.8%-37.7%). Work productivity loss and activity impairment significantly decreased over time and were associated with disease activity, but not with IBD type or child's age. Caregivers' HRQOL was associated with both impairments. Costs related to work absenteeism were at least €6272 ($7276) per patient during the first year after diagnosis., Conclusions: Caregivers of children with IBD experience significant impairments in work and daily activities, especially at diagnosis. The impact decreases thereafter and is associated with disease activity and caregivers' HRQOL. Work absenteeism results in high indirect costs., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors., Methods: From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. IBD details [type, Paris classification, clinical and biochemical disease activity, treatment] and VTE details [type, location, treatment, outcome] were collected. To estimate VTE incidence, participants annually reported the number of PIBD patients, data source and catchment area of their centre. A systematic literature review and meta-analysis was performed to calculate the VTE incidence in the general paediatric population., Results: Participation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn's disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27-5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18-0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients., Conclusion: There is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Introduction: High-quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented, and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine., Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach., Results: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high-quality procedures. These were subcategorized into three subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators), and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, "rate of adequate bowel preparation," was set at ≥80%., Discussion: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement., Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach., Results: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high-quality endoscopic care in children. These standards were subcategorized into three subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards)., Discussion: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high-quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports., Methods: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus., Results: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report., Discussion: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children., Methods: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach., Results: The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%)., Discussion: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer, and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process., Methods: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach., Results: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49)., Conclusions: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority., Competing Interests: Conflicts of interest: P.B. has served on the advisory boards of Biocodex, Nutricia, and Avanos. P.B. has received honoraria for speaking engagements from AbbVie, Nutricia, and Avanos. N.M.C.'s institution received speaker fees, advisory board fees, and research funding on his behalf from AbbVie, Eli Lilly, Takeda, Shire, Pfizer, and 4D Pharma. D.S.F. has received royalties from UpToDate (“Pediatric Caustic Ingestions”). I.H. has received honoraria for speaking engagements from BioGaia, Oktal Pharma, Nutricia, Abela Pharm, and Nestle. H.Q.H. has received research support from Janssen, AbbVie, Takeda, and Allergan. H.Q.H. has served on the advisory boards of AbbVie and Jansen. K.J. has received research support from Janssen, AbbVie, and the Center for Drug Research and Development (CDRD). K.J. has served on the advisory boards of Janssen, AbbVie, and Merck and participates in the speaker's bureau for AbbVie and Janssen. D.G.L. has received consultant fees from EvoEndo. J.R.L. has received research support from AbbVie and an honorarium from Mead Johnson. A.R.O. has received research support from Janssen, AbbVie, Pfizer and Eli Lilly. A.R.O. has served on the advisory boards of Janssen, AbbVie, and Eli Lilly and participates in the speaker's bureau for AbbVie and Janssen. J.R.R. has received research support from AbbVie and Janssen. J.R.R. has served on the advisory boards of Janssen, BMS, Eli Lilly, and Pfizer. C.M.W. has received research support from AbbVie., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2., Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFα) drug, stricture and surgery., Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNFα earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2., Conclusions: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Biologic treatment options are limited for children with ulcerative colitis. The aim of this study was to assess the safety and efficacy of adalimumab in children with moderate-to-severe ulcerative colitis., Methods: The double-blind ENVISION I study was done at 24 hospitals in ten countries. Children (4-17 years) with moderate-to-severe ulcerative colitis despite stable doses of concurrent treatment with oral corticosteroids or immunosuppressants were enrolled. Per the original study design, patients were randomly assigned with an Interactive Voice Response System (IVRS) to receive either high-dose induction adalimumab (2·4 mg/kg [maximum 160 mg] at weeks 0 and 1) or standard-dose induction adalimumab (2·4 mg/kg at week 0 and placebo at week 1); both groups received 1·2 mg/kg (maximum 80 mg) at week 2 and 0·6 mg/kg (maximum 40 mg) at weeks 4 and 6. Patients with partial Mayo score (PMS) response at week 8 (defined as a decrease of two or more points and a decrease of ≥30% from baseline in PMS) were randomly assigned (2:2:1)-using IVRS-to receive either high-dose maintenance adalimumab (0·6 mg/kg weekly), standard-dose maintenance adalimumab (0·6 mg/kg every other week), or placebo up to week 52 (random assignment to the placebo group was ceased mid-trial, as was randomisation in the induction phase with all subsequent patients receiving open-label high-dose induction adalimumab). Coprimary endpoints were the proportion of patients with PMS remission at week 8 (intent-to-treat [ITT]-E population, not including those patients who were not randomised in the induction phase) and full Mayo score (FMS) remission at week 52 in week 8 PMS responders (maintenance ITT-E [mITT-E] population), for which the pooled adalimumab group (patients who received high-dose or standard-dose adalimumab) and the individual dose groups were compared against external adult placebo rates. We report results of the final confirmatory analysis. This trial is registered with ClinicalTrials.gov, NCT02065557., Findings: 93 children were recruited between Oct 13, 2014, and Sept 5, 2018, to the main study (77 [83%] were randomly assigned [double-blind] to receive high-dose or standard-dose induction adalimumab; 16 [17%] received open-label high-dose induction adalimumab after study design change). At week 8, 74 (80%) children who were PMS responders continued to the maintenance period. 62 (84%) patients were randomly assigned to receive high-dose or standard-dose maintenance adalimumab treatment; 12 (16%) patients received placebo. In patients in the ITT-E population who were randomly assigned to receive high-dose induction adalimumab, a significantly higher proportion of patients were in PMS remission at week 8 (28 [60%] of 47) compared with external placebo (19·8%; p=0·0001). 13 (43%) of 30 patients in the standard-dose induction adalimumab group were in PMS remission at week 8 versus an external placebo rate of 19·8%, but this difference was not significant (p=0·38). Similarly, FMS remission at week 52 in children who were week 8 PMS responders was reported in a significantly higher proportion of patients in mITT-E population who received high-dose maintenance adalimumab (14 [45%] of 31 patients) versus external placebo at week 52 (18·4%; p=0·0001). Nine (29%) of 31 patients in the standard-dose maintenance adalimumab group were in FMS remission at week 52 versus an external placebo rate of 18·4%, but this difference was not significant (p=0·38). Remission rates in the pooled adalimumab groups were significantly better compared with external placebo (PMS remission at week 8: 41 [53%] of 77 patients; p<0·0001; FMS remission at week 52: 23 [37%] of 62 patients; p=0·0001). 21 (23%) of 93 patients in the main study had one or more treatment-emergent serious adverse events during any adalimumab exposure. The most common adverse events were headache, anaemia, and ulcerative colitis flare during the induction period and ulcerative colitis flare, headache, and nasopharyngitis during the maintenance period., Interpretation: Clinically meaningful rates of remission and response were reported in children who received adalimumab in this study. No new safety signals were observed, suggesting that adalimumab is an efficacious and safe treatment option for children with moderate-to-severe ulcerative colitis., Funding: AbbVie., Competing Interests: Declaration of interests NMC reports speaker fees from AbbVie; advisory board fees from AbbVie and Eli Lilly; research funding from AbbVie, Eli Lilly, Shire, Takeda, Janssen, and Pfizer; and writing support from AbbVie. WAF reports consulting fees from Boehringer Ingelheim, Takeda, AbbVie, Janssen, and Robarts. JK reports consultation fees from Nestle; research grants from Nutricia; and honoraria from Bristol Myers Squibb, Nestle, Nutricia. FMR reports grants and research support from Nestlé, AbbVie, MSD, and Janssen; served as a member of advisory boards for Centocor (DEVELOP), AbbVie (CAPE and LEA), MSD France (SAC), Nestlé, Danone, Mead Johnson, Nutricia, Takeda, Celgene, Biogen, Shire, Pfizer, and Therakos; and reports payment and honorarium for lectures from AbbVie, Danone, Nutricia, and Nestlé. NMM, MV, TF-H, YSG, MB, and AL are full-time AbbVie employees and might own AbbVie stock and stock options. DT reports consultation fees and honoraria from Janssen, Pfizer, Ferring, AbbVie, Takeda, Biogen, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, Bristol Myers Squibb; research support from Janssen, Ferring, AbbVie, and Takeda; and royalties from Hospital for Sick Children. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections., Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020., Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001)., Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy., Trial Registration Number: ISRCTN45176516., Competing Interests: Competing interests: NAK reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Takeda, personal fees and non-financial support from Dr Falk, outside the submitted work. JRG reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. DC reports non-financial support from Ferring, personal fees and non-financial support from Pfizer, outside the submitted work. SL reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. RC reports personal fees from Takeda, outside the submitted work. NMC reports trial funding, advisory board and speaker fees paid to his institution from AbbVie, Eli Lilly, Takeda, Shire, Pfizer and Janssen. ALH reports personal fees from Abbvie, personal fees from Allergan, personal fees from BMS, personal fees from Celltrion, personal fees from Falk, personal fees from GSK, personal fees from Takeda, personal fees from Pfizer, personal fees from Janssen, personal fees from Galapogos, personal fees from Astra Zeneca, outside the submitted work. PMI reports grants and personal fees from Takeda, grants from MSD, grants and personal fees from Pfizer, personal fees from Galapagos, personal fees from Gilead, personal fees from Abbvie, personal fees from Janssen, personal fees from Boehringer Ingelheim, personal fees from Topivert, personal fees from VH2, personal fees from Celgene, personal fees from Arena, personal fees from Samsung Bioepis, personal fees from Sandoz, personal fees from Procise, personal fees from Prometheus, outside the submitted work. KBK reports personal fees from Janssen, personal fees from Takeda, personal fees from PredictImmune, personal fees from Amgen, outside the submitted work. CAL reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr Falk Pharma, grants from AstraZeneca, outside the submitted work. JKL reports personal fees from MSD, personal fees from Janssen, grants and personal fees from Takeda, grants and personal fees from Galapagos, personal fees from Tillotts, outside the submitted work. JM reports grants and personal fees from Takeda Pharmaceuticals, grants and personal fees from Biogen, personal fees and non-financial support from AbbVie, personal fees from Grifols, personal fees from Sandoz, personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Vifor Pharmaceuticals, personal fees from Predictimmune, personal fees from Bristol Myers Squibb, non-financial support from Ferring Pharmaceuticals, outside the submitted work. DPBM reports grants from the Leona M. and Harry B. Helmsley Charitable Trust, during the conduct of the study; personal fees from Takeda Pharmaceuticals, personal fees from Pfizer, personal fees from Bridge Biotherapeutics, personal fees from Palatin Technologies, personal fees from Boehringer-Ingelheim, personal fees and other from Prometheus Biosciences, personal fees from Gilead, outside the submitted work. KVP reports personal fees and non-financial support from Takeda, personal fees and non-financial support from Janssen, personal fees and non-financial support from Abbvie, personal fees from DrFalk, non-financial support from Ferring, outside the submitted work. RCGP reports acting as consultant, advisory board member, speaker or recipient of educational grant from Dr Falk, Ferring, Janssen, Pharmacosmos and Takeda. TR reports grants and personal fees from Abbvie, personal fees from BMS, personal fees from Celgene, personal fees from Ferring, personal fees from Gilead, personal fees from GSK, personal fees from LabGenius, personal fees from Janssen, personal fees from Mylan, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sandoz, personal fees from Takeda, personal fees from Galapagos, personal fees from Arena, outside the submitted work. RKR reports grants from NHS Research Scotland Senior Research Fellowship, personal fees from Nestlé, personal fees from AbbVie, personal fees from Dr Falk, personal fees from Takeda, personal fees from Napp, personal fees from Mead Johnson, personal fees from Nutricia, personal fees from 4D Pharma, outside the submitted work. CPS reports grants and personal fees from AbbVie, grants and personal fees from Janssen, grants and personal fees from Takeda, personal fees from Dr Falk, personal fees from Pfizer, personal fees from Galapagos, personal fees from Arena, personal fees from Fresenius Kabi, outside the submitted work. PJS reports speaker fees and advisory board sponsorship from Janssen, Celltrion and Takeda outside the submitted work. CWL reports personal fees from Abbvie, personal fees from Janssen, personal fees from Pfizer, personal fees from Takeda, grants from Gilead, personal fees from Gilead, personal fees from Galapagos, personal fees from Iterative Scopes, personal fees from Trellus Health, personal fees from Celltion, personal fees from Ferring, personal fees from BMS, during the conduct of the study. SS reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Phamrmacocosmos, outside the submitted work. NP reports personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Abbvie, personal fees from Roche, personal fees from Lilly, personal fees from Allergan, personal fees from Celgene, outside the submitted work; and NP has served as a speaker/advisory board member for Abbvie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. TA reports grants and non-financial support from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen Inc, grants and personal fees from Celltrion Healthcare, personal fees and non-financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non-financial support from Tillotts, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years)., Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished., Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD's National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected., Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children's school attendance and parents' productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument., Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children's and parents' QoL (EuroQol 5-Dimension questionnaires), children's school attendance, and parents' productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial., Trial Registration: ClinicalTrials.gov NCT02852694; https://clinicaltrials.gov/ct2/show/NCT02852694., (©Mattias Neyt, Annick Christiaens, Marina Aloi, Lissy de Ridder, Nicholas M Croft, Sibylle Koletzko, Arie Levine, Dan Turner, Richard K Russell, Frank M Ruemmele, Gigi Veereman. Originally published in JMIR Formative Research (http://formative.jmir.org), 25.01.2021.)

Introduction: Patients with paediatric-onset inflammatory bowel disease (PIBD) may develop a complicated disease course, including growth failure, bowel resection at young age and treatment-related adverse events, all of which can have significant and lasting effects on the patient's development and quality of life. Unfortunately, we are still not able to fully explain the heterogeneity between patients and their disease course and predict which patients will respond to certain therapies or are most at risk of developing a more complicated disease course. To investigate this, large prospective studies with long-term follow-up are needed. Currently, no such European or Asian international cohorts exist. In this international cohort, we aim to evaluate disease course and which patients are most at risk of therapy non-response or development of complicated disease based on patient and disease characteristics, immune pathology and environmental and socioeconomic factors., Methods and Analysis: In this international prospective observational study, which is part of the PIBD Network for Safety, Efficacy, Treatment and Quality improvement of care (PIBD-SETQuality), children diagnosed with inflammatory bowel disease <18 years are included at diagnosis. The follow-up schedule is in line with standard PIBD care and is intended to continue up to 20 years. Patient and disease characteristics, as well as results of investigations, are collected at baseline and during follow-up. In addition, environmental factors are being assessed (eg, parent's smoking behaviour, dietary factors and antibiotic use). In specific centres with the ability to perform extensive immunological analyses, blood samples and intestinal biopsies are being collected and analysed (flow cytometry, plasma proteomics, mRNA expression and immunohistochemistry) in therapy-naïve patients and during follow-up., Ethics and Dissemination: Medical ethical approval has been obtained prior to patient recruitment for all sites. The results will be disseminated through peer-reviewed scientific publications., Trial Registration Number: NCT03571373., Competing Interests: Competing interests: MAA received consultation fee and honorarium from Abbvie. SK received consultation fee, research grant or honorarium from Danone, Nestec-Nutrition, Abbvie, Takeda, Celgene, Shire, Pfizer, Biogaia, Janssen, Berlin-Chemie, Mead Johnson, Vifor, Pharmacosmos and ThermoFisher. RKR is supported by an NHS Research Scotland Senior Research Fellowship and has received speakers’s fees, travel support, and/or participated in medical board meetings with Nestle, MSD Immunology, AbbVie, Dr Falk, Takeda, Napp, Mead Johnson and Nutricia&4D Pharma. FR has received speaker fees from Shering-Plough, Nestlé, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor and AbbVie; has served as a board member for SAC:DEVELOP (Johnson & Johnson), CAPE (AbbVie), LEA (AbbVie); and has been invited to MSD France, Nestlé Nutrition Institute, Nestlé Health Science, Danone, MeadJohnson, Takeda, Celgene, Biogen, Shire, Pfizer and Therakos. NMC (into employer’s investigator accounts) received speaker fees, advisory board fees and research funding from Eli-Lilly, Takeda, Abbvie Shire Pfizer and 4D Pharma. LdR had collaborations (such as involved in industry-sponsored studies, investigator-initiated study and consultancy) with Shire, Malinckrodt, Nestlé, Celltrion, Abbvie and Pfizer; and received a grant from ZonMw, ECCO and Pfizer. Remaining authors: no competing interests declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Immunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn's disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups., Aims: To compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation., Methods and Analysis: REDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6-17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk)., Ethics and Dissemination: ClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access., Trial Registration Number: NCT02852694; Pre-results., Competing Interests: Competing interests: RKR is supported by an NHS Research Scotland Senior Research Fellowship, and has received speaker’s fees, travel support and/or participated in medical board meetings with Nestle, MSD Immunology, AbbVie, Dr Falk, Takeda, Napp, Mead Johnson, Nutricia & 4D Pharma. FMR has received speaker fees from Shering-Plough, Nestlé, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor, AbbVie; has served as a board member for SAC:DEVELOP(Johnson & Johnson), CAPE (AbbVie), LEA (AbbVie); and has been invited to MSD France, Nestlé Nutrition Institute, Nestlé Health Science, Danone, MeadJohnson, Takeda, Celgene, Biogen, Shire, Pfizer and Therakos. DT received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Biogen, Atlantic Health, Shire, Celgene, Lilly, Neopharm, Roche. LdR received consultation fee, research grant, or honorarium from ZonMw, ECCO, Shire, Malinckrodt, Nestlé, Celltrion, Abbvie and Pfizer. MA received consultation fee and honorarium from Abbvie. SK received consultation fee, research grant, or honorarium from Danone, Nestec-Nutrition, Abbvie, Takeda, Celgene, Shire, Pfizer, Biogaia, Janssen, Berlin-Chemie; Mead Johnson, Vifor, Pharmacosmos, ThermoFisher, (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 -10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 -10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Background and Aim: Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC., Methods: This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point., Results: Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk., Conclusions: High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC., Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits., Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%)., Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042&#95;video1izy042.video15769503407001.

Objectives: Paediatric endoscopy is an important diagnostic tool; however, there is little published data to guide clinicians in selecting patients for endoscopy. This study aimed to evaluate a single centre's experience of newly presenting children focusing on presenting symptoms, investigations, and diagnostic yield., Methods: Clinical factors and endoscopic plus histological findings over a 6-month period were assessed. Only first diagnostic endoscopies were included. All biopsies were reviewed in a weekly histopathology multidisciplinary team meeting with a final agreed outcome. Abnormal histology was used as the criterion standard for reporting abnormality., Results: A total of 218 endoscopies were reviewed in 164 children. Approximately 65% were histologically normal (49% of children had macroscopically and histologically normal findings). Macroscopic and histological abnormalities (respectively) were 44% and 28% of oesophagogastroduodenoscopy (OGD) patients, 25% and 25% of colonoscopy alone, and 53% and 53% of those undergoing both OGD and colonoscopy (OGD&Col). For OGD-only patients, excluding those with raised anti-tissue transglutaminase antibodies, vomiting led to the highest rate of abnormal histology (22%). For colonoscopy-only and OGD&Col patients, per rectum bleeding led to the highest rates of abnormal histology (14% and 29%, respectively), after excluding those with laboratory abnormalities (anaemia and raised erythrocyte sedimentation rate) suggestive of inflammatory bowel disease., Conclusions: This study showed that half of all first diagnostic endoscopies in our unit had neither macroscopic nor histological abnormalities. There was discrepancy between macroscopic abnormalities and histological findings in OGD. Prospective studies are needed to develop guidelines in appropriately predicting abnormality and selecting patients for endoscopy.

Objective: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK)., Methods: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index., Results: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28 = only "fair agreement"; P < 0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (n = 385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (P = 0.01); however, pre and post anti-TNF data collection was not over equal time periods., Conclusions: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.