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Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD.VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/mBetween May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 μg/mL [IQR 5·5-18·1] vs 5·9 μg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 μg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/mVedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/mThe European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome.Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented.In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P0.001]. Combined CS-free clinical and biomarker remission (CRP5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P0.001).Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.

Background Patients with inflammatory bowel disease (IBD) often use the Internet to seek information beyond that received from healthcare professionals. This study assessed the perceptions of YouTube presenters on the role of diet in the management of IBD. Methods Videos discussing dietary aspects (food, diet-related items, and advisory comments [FODRIACs]) in the management of IBD were included. The perceptions of presenters toward each FODRIAC were labeled as positive, negative, or neutral/intermediate, and FODRIACs were classified according to their underlying role in the management of IBD (eg, symptom management, gut inflammation). Subgroup analysis was performed by type of video presenter (patients vs healthcare professionals), type of IBD (Crohn’s disease vs ulcerative colitis), and reporting of scientific evidence supporting presenters’ perceptions. Results We identified 122 FODRIACs within 160 videos. Patient videos received a higher number of likes (median 85 [interquartile range, 35-156]) than healthcare professional videos (median 44 [interquartile range, 16-1440]) (P = .01). Scientific evidence was cited in 2 (3%) of 76 patient videos compared with 25 (35%) of 71 healthcare professional videos (P < .001). Positive perceptions were expressed about avocadoes, salmon, bananas, white bread, and rice, whereas negative perceptions were reported for processed, high-fat and high-sugar foods and carbonated drinks. Fewer negative perceptions were expressed in videos supported by scientific evidence than in videos that lacked evidence (scientific: 4 positive, 0 negative vs nonscientific: 7 positive, 20 negative; P = .01). Conclusions We have identified FODRIACs proposed as beneficial or detrimental in the management of IBD. The effect this information has on dietary practice as patients with IBD self-manage their condition needs further exploration.

Background and Aims Treatment adherence is key to the efficacy of exclusive enteral nutrition [100% EN] in active Crohn’s disease [CD], but there are no biomarkers to objectively estimate this. We explored faecal parameters as biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive Enteral Nutrition Index of Compliance [GENIE]. Methods Healthy adults replaced all [100% EN] or part [85% EN, 50% EN, 20% EN] of their diet with a formula for 7 days. Faecal pH, water content, short chain fatty acids, and branched chain fatty acids [BCFAs] were measured before [D0] and after [D7] each intervention. Optimal biomarkers and threshold values were derived using receiver operating characteristic curve analyses and machine learning to develop the GENIE. The GENIE was then validated in 30 CD children, during and after 100% EN. Results In all, 61 adults were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from Conclusions GENIE can help predict adherence to 100% EN and may complement current conventional dietary assessment.

Genomic medicine enables the identification of patients with rare or ultra-rare monogenic forms of inflammatory bowel disease (IBD) and supports clinical decision making. Patients with monogenic IBD frequently experience extremely early onset of treatment-refractory disease, with complex extraintestinal disease typical of immunodeficiency. Since more than 100 monogenic disorders can present with IBD, new genetic disorders and variants are being discovered every year, and as phenotypic expression of the gene defects is variable, adaptive genomic technologies are required. Monogenic IBD has become a key area to establish the concept of precision medicine. Clear guidance and standardised, affordable applications of genomic technologies are needed to implement exome or genome sequencing in clinical practice. This joint British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition guideline aims to ensure that testing resources are appropriately applied to maximise the benefit to patients on a national scale, minimise health-care disparities in accessing genomic technologies, and optimise resource use. We set out the structural requirements for genomic medicine as part of a multidisciplinary team approach. Initiation of genomic diagnostics should be guided by diagnostic criteria for the individual patient, in particular the age of IBD onset and the patient's history, and potential implications for future therapies. We outline the diagnostic care pathway for paediatric and adult patients. This guideline considers how to handle clinically actionable findings in research studies and the impact of consumer-based genomics for monogenic IBD. This document was developed by multiple stakeholders, including UK paediatric and adult gastroenterology physicians, immunologists, transplant specialists, clinical geneticists, scientists, and research leads of UK genetic programmes, in partnership with patient representatives of several IBD and rare disease charities.

Background and Aims:The incidence of paediatric-onset inflammatory bowel disease (PIBD) continues to rise globally. We aimed to determine whether mode of delivery, gestational age at birth, or type of infant feeding contribute to the development of PIBD in a nationwide cohort of Scottish children.Methods:All children born in Scotland between 1981-2017 were identified using linked health administrative data to determine mode of delivery, gestational age at birth, and type of infant feeding. PIBD cases were defined as onset of Crohn’s disease (CD), ulcerative colitis (UC) or IBD-unclassified (IBDU) before age 16 years. Validation was performed within an entire Scottish health board (16% of total population) via individual case-note verification. Hazard ratios (HR) were calculated for each exposure using Cox proportional hazards models.Results:A study population of 2,013,851 children was identified including 1,721 PIBD cases. Validation of 261 PIBD patients coded as CD and/or UC identified 242 (93%) as true positive. Children delivered vaginally did not have an altered risk of developing PIBD compared to those delivered by caesarean section; adjusted HR 0.95 [95% CI 0.84-1.08] (p=0.46). Compared to children born at term (≥37 weeks), children born prematurely did not have an altered risk of developing PIBD; 24-31 weeks gestation HR 0.99 [95% CI 0.57-1.71] (p=0.97); 32-36 weeks gestation HR 0.96 (95% CI 0.76-1.20] (p=0.71). Compared to children exclusively breast fed at age 6 weeks, children exclusively formula fed did not have an altered risk of developing PIBD; adjusted HR 0.97 [95% CI 0.81-1.15] (p=0.69).Conclusions:This population-based study demonstrates no association between mode of delivery, gestational age, or exclusive formula feeding at 6 weeks and the development of PIBD.

Background The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn’s disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. Methods Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn’s disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. Results Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. Conclusions This pilot study identified potential dietary triggers of gut inflammation in children with Crohn’s disease after food reintroduction following treatment with exclusive enteral nutrition. Trial registration: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).

OBJECTIVE To evaluate the impact of structured transition from pediatric to adult inflammatory bowel disease (IBD) services on objective patient outcomes, including disease flares, admission rates, and healthcare resource use. METHODS A retrospective observational study in 11 United Kingdom gastroenterology centers. Transition patients attended ≥2 visits to the gastroenterology service with both pediatric and adult personnel jointly present; non-transition patients transferred to adult services without joint visits. Data were collected from medical records for the 12-month periods before and after the date of the first visit involving adult IBD services (index visit). RESULTS A total of 129 patients were included: 95 transition patients and 34 non-transition patients. In the 12 months post-index visit, transition patients had fewer disease flares (P = 0.05), were more likely to be steroid-free (71% versus 41%, P

Patients enrolled in randomised controlled trials (RCTs) may differ from the target population due to restricted eligibility criteria. To compare treatment response to biologics in routine practice for children with inflammatory bowel diseases (IBD) who would and would not have been eligible for enrolment in the regulatory RCT of the same drug. We enrolled children with IBD who initiated adalimumab, infliximab, vedolizumab or ustekinumab. The eligibility criteria as defined in the RCT of the corresponding biologic were applied to each patient. The primary outcome was 12-month steroid-free remission (SFR) without switching biologics or undergoing surgery. We screened 289 children (198 [68%] with Crohn's disease [CD], 91 [32%] with ulcerative colitis [UC]) with 326 initiations of biologics. Only 62 of 164 (38%) children with moderate-to-severe disease would have been eligible for inclusion in the original RCTs. The SFR rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2-4.5]; p = 0.01). The main exclusion criterion was prohibited previous therapies (47%). Ineligible CD patients were older, more often had a family history of IBD and had higher levels of CRP than eligible children; in UC there were no differences between the groups. Most children with IBD who initiate biologics would not have been eligible to be included in the corresponding regulatory RCTs. The outcomes of ineligible patients were worse than for eligible patients. Results from RCTs should be interpreted with caution when applied to clinical practice.

Background: The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing. Aims: To identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti-tumour necrosis factor alpha (anti-TNFα) agents. Methods: We captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed

BACKGROUND: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups. METHODS: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists). RESULTS: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries. CONCLUSIONS: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.

OBJECTIVES: To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process. METHODS: A web-based, 43-question survey. RESULTS: Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130-300] per centre). Routine use of co-immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) ([61/70, 87.1%] compared with [23/70, 32.9%]; P

ObjectiveWe aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn’s disease [CD].MethodsWe formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.ResultsWe established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone.ConclusionsWe present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.

OBJECTIVES The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. METHOD This was a retrospective study of all gastroenterology patients

It remains unclear whether suboptimal response to exclusive enteral nutrition (EEN) in some children with Crohn's disease (CD) is explained by poor compliance. The current study measured faecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3–17 years) with CD, and explored associations with faecal calprotectin (FC) levels at 33 and 54 days of EEN. FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: -743 mg/kg, 54 days: -1043 mg/kg, p < 0.001), but not in patients who had detectable levels. At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (p = 0.042) and demonstrated a greater decline from baseline FC (-69% vs +5%, p = 0.011). Poorer response to EEN is explained in part by diminished compliance. Faecal GIP might be useful as proxy biomarker of EEN compliance.

Background Anti-TNF drugs increase the risk of serious respiratory infections and impair protective immunity following pneumococcal, influenza, and viral hepatitis vaccinations. Therefore, we sought to determine whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses following SARS-CoV-2 infection. Methods CLARITY IBD is a multicentre, prospective observational cohort study. Antibody responses in participants treated with infliximab were compared to 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 22nd September and 23rd December 2020. Nucleocapsid anti-SARS-CoV2 antibodies were measured using the Roche Elecsys assay. Clinical data and serum were collected every 8 weeks. Durability was defined as nonreduction in antibody level by at least 50% from baseline. Results At baseline, rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab- than vedolizumab-treated patients (3.4% [161/4685], vs 6.0% [134/2250], p Conclusion Seroprevalence, seroconversion in PCR-confirmed cases, and the magnitude and durability of anti-SARS-CoV2 antibodies were reduced in infliximab- compared with vedolizumab-treated patients. Serological testing and virus surveillance should be considered in patients treated with anti-TNF drugs to detect suboptimal vaccine responses, persistent infection, and viral evolution to inform public health policy.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15–80 µg/L], C-reactive protein [CRP] [ >100mg/L for >10 days, normal 0–5 mg/L], erythrocyte sedimentation rate [ESR] consistently >100mm/h [normal 0–15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.

Background: Muscle–bone deficits are common in pediatric Crohn’s disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn’s disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn’s disease compared with healthy controls. Methods: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine. Muscle function and biomarkers of the muscle-bone unit were also assessed. Results: Twenty-seven adults with Crohn’s disease with median (range) age 23.2 years (18.0, 36.1) and 27 age and sex-matched controls were recruited. Trabecular microarchitecture, cortical geometry and BMA were not different between Crohn’s disease and controls (P > 0.05 for all). Muscle area was lower (P = 0.01) and muscle fat fraction was higher (P = 0.04) at the distal femur in Crohn’s disease compared to controls. Crohn’s disease participants had lower grip strength [-4.3 kg (95% confidence interval (CI), -6.8 to -1.8), P = 0.001] and relative muscle power [-5.0 W/kg (95% CI, -8.8 to -1.2), P = 0.01]. Crohn’s disease activity scores negatively associated with trabecular bone volume (r = -0.40, P = 0.04) and muscle area (r = -0.41, P = 0.03). Conclusion: Young adults with well-controlled Crohn’s disease managed with contemporary therapies did not display abnormal bone microarchitecture or geometry at the distal femur but exhibited muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function warrant investigation.

IntroductionThe PIBD-classes criteria were developed to standardise the classification of children with inflammatory bowel disease [IBD], from Crohn’s disease [CD], through IBD-unclassified [IBD-U], to typical ulcerative colitis [UC]. We aimed to further validate the criteria and to explore possible modifications.MethodsThis was a multicentre retrospective cohort study of children diagnosed with IBD with at least 1 year of follow-up. Clinical, radiological, endoscopic, and histological data were recorded at diagnosis and latest follow-up, as well as the 23 items of the PIBD-classes criteria. The PIBD-classes criteria were assessed for redundant items, and a simplified algorithm was proposed and validated on the original derivation cohort from which the PIBD-classes algorithm was derived.ResultsOf the 184 included children [age at diagnosis 13 ± 3 years, 55% males], 122 [66%] were diagnosed by the physician with CD, 17 [9%] with IBD-U, and 45 [25%] with UC. There was high agreement between physician-assigned and PIBD-classes generated diagnosis for CD [93%; eight patients moved to IBD-U] and for UC [84%; six moved to IBD-U and one to CD]. A simplified version of the algorithm with only 19 items is suggested, with comparable performance to the original algorithm [81% sensitivity and 81% specificity vs 78% and 83% for UC; and 79% and 95% vs 80% and 95% for CD, respectively].ConclusionsThe PIBD-classes algorithm is a useful tool to facilitate standardised objective classification of IBD subtypes in children. A modified version of the PIBD-classes maintains accuracy of classification with a simplified algorithm.

IntroductionIncreased risk of opportunistic infection—e.g., varicella zoster infection—secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population.MethodsData regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009–2018].ResultsIn all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; p ConclusionsHigh rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies.

OBJECTIVES The aim of the study was to evaluate the use of steroids within the paediatric inflammatory bowel disease (PIBD) population at a tertiary paediatric centre over a year; to identify cases of steroid dependency; and assess factors associated with steroid excess. METHODS The prevalent PIBD population (May 1, 2017-April 30, 2018) were reviewed. Data were collected retrospectively from patient records and entered into an online steroid assessment tool (modified for paediatrics). RESULTS A total of 229 patients (181 Crohn disease, 31 ulcerative colitis [UC], and 17 inflammatory bowel disease-unclassified) were included. Of the 229 patients 38 (16.6%) received oral steroids; 12 of 38 (31.6%) receiving >3-month course. Eleven of 38 (28.9%) received >1 steroid course (maximum 2). Of the 229 patients 37 (16.2%) had exclusive enteral nutrition, with 26 of 37 (11.4% total cohort) avoiding steroid use during the study period.Quiescent disease activity had a negative correlation with steroid use (11/127 [8.7%] vs 27/102 [26.5%] P

Background & aims: \ud Interpretation of blood micronutrient levels requires age-appropriate reference intervals. This study developed age-dependent micronutrient centiles for healthy children (HC) and explored their utility in sick children.\ud \ud Methods: \ud 244 blood samples were collected from normal HC who underwent tests for acute illness. Age-dependent, centile charts were fitted for zinc, copper, magnesium and selenium in plasma and erythrocytes (RBC), and for vitamins B1, B2 and B6 in RBC. For 34 children with Crohn's disease (CrD) and 55 with coeliac disease (CoeD), Z-scores for the levels of these micronutrients were computed, using the new charts. Associations were explored between plasma and RBC micronutrient Z-scores, and in CrD with CRP and serum albumin.\ud \ud Results: \ud In HC, plasma zinc and selenium increased and plasma copper, magnesium and RBC vitamins B1, B2 and B6 decreased with age. In HC and in CrD, plasma and RBC Z-scores for copper, selenium and magnesium (all p < 0.001) were positively correlated, but not for zinc. In CrD, albumin was related with plasma zinc (rho = 0.62; p < 0.001) and selenium Z-scores (rho = 0.65; p < 0.001) and plasma copper Z-score with CRP (rho = 0.45; p = 0.02). A higher proportion of CrD children had low levels for B2 (21% vs 0%; p = 0.01) and B6 (18% vs 0%; p = 0.02) using the new centile charts than the local laboratory references.\ud \ud Conclusion: \ud Age-dependent micronutrient centile charts enable tracking of micronutrient status, Z-score calculation and may prevent misdiagnosis and inappropriate treatment of deficiencies. In systemic inflammatory conditions, RBC measurements of certain micronutrients may be more reliable to use than measurements in plasma.

Cross-sectional imaging is important in the assessment of transmural inflammation in Crohn's disease (CD). Small bowel involvement is often more extensive in pediatric CD, requiring a panentering measuring tool. We undertook to develop a magnetic resonance enterography (MRE)-based index that would measure inflammation in all segments of the intestine, without rectal contrast.Children with CD underwent ileocolonoscopy and MRE and half were prospectively followed for 18 months when MRE was repeated. Item generation and reduction were performed by a Delphi panel of pediatric radiologists, a systematic literature review, a cross-sectional study of 48 MREs, and a steering committee. Formatting and weighting were performed using multivariate modeling adjusted by a steering committee. MREs were read locally and centrally. Reliability, validity, and responsiveness were determined using several clinimetric and psychometric approaches.Thirty items were initially generated and reduced to 5 using regression analysis on 159 MREs: wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign. In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r = 0.85; P.001) and with the simple endoscopic score in a subsample with ileocolonic disease (r = 0.63; P.001). Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84; 95% confidence interval [CI], 0.79-0.87; and 0.81, 95% CI, 0.65-0.90, respectively; both P.001). Excellent responsiveness was found at repeated visits (n = 116 MREs; area under the receiver operating characteristic curve 0.96; 95% CI, 0.93-0.99). Transmural healing was defined as PICMI ≤10 and response as a change of20 points with excellent discriminative validity (area under the receiver operating characteristic curve = 0.96; 95% CI, 0.93-0.99).The PICMI is a valid, reliable, and responsive index for assessing transmural inflammation in pediatric CD. It scores the entire bowel length and does not require intravenous contrast or rectal enema and, therefore, is suitable for use in children. (ClinicalTrials.gov, Number: NCT01881490.).

The use of thiopurine therapy in Epstein-Barr virus (EBV)-naive inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P = 0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.

BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS:We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p

Biologic therapies have changed the outcome of both adult and pediatric patients with Inflammatory Bowel Disease (IBD). In September 2013, the first biosimilar of infliximab was introduced into the pharmaceutical market. In 2015, a first position paper on the use of biosimilars in pediatric IBD was published by the ESPGHAN IBD Porto group. Since then, more data have accumulated for both adults and children demonstrating biosimilars are an effective and safe alternative to the originator. In this updated position statement, we summarize current evidence and provide joint consensus statements regarding the recommended practice of biosimilar use in children with IBD. ispartof: JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION vol:68 issue:1 pages:144-153 ispartof: location:United States status: published

The safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P 0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.

Background It is important to identify patients with monogenic IBD since management including response to biologics and surgery plus the role of stem cell transplantation may differ from classical IBD. We report on the 2020 Position paper of the PORTO group of ESPGHAN for the use of genomics to diagnose monogenic causes of IBD. Methods Paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia reached a consensus of standard of care. Our systematic literature review covered indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. Results Next-generation DNA sequencing technologies are recommended to diagnose monogenic causes of IBD in routine clinical practice, embedded in the setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients but instead genetic testing should be considered in the context of age of IBD onset (infantile IBD, very early onset IBD, paediatric or young adult IBD) and on further key criteria such as family history, relevant comorbidities and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We present a diagnostic algorithm that includes a gene panel of seventy-five monogenic IBD genes. We discuss how these recommendations can be implemented from 2021 onwards into the UK NHS health care system. Lastly, we present a UK-focused health care utilisation pathway highlighting the available UK clinical resources, clinical targeted panel sequencing and exome sequencing strategies in the UK, and regional immune validation pathways. Summary Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD in the UK.

Background Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice. Methods We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD. Results In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn’s disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5–23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment. Conclusions A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.

Introduction Treatment with exclusive enteral nutrition (EEN) offers a nutritional therapy paradigm in Crohn’s disease, with the extensive modulation of gut microbiome being its proposed mechanism of action(1). Recent studies propose variable clinical efficacy for 85% EN (Cheat EN/CEN), 50% EN (Partial EN/PEN) and 20% EN (maintenance EN/MEN), and a dose-dependent effect of EN use in CD(2–4). Therefore, this study aims to investigate the dose-dependent effect of 100%, 85%, 50%, and 20% EN on faecal microbial metabolites; and to investigate if this effect can be used as a compliance marker for EEN. Methods Healthy adults followed EEN, CEN, PEN or MEN diet for 7 days. Fresh faecal samples were collected before and after each dietary intervention. Dietary assessment was performed throughout the intervention using estimated weight food diaries. Faecal pH, Bristol Stool Chart Score (BSCS), short chain fatty acids and hydrogen sulphide were measured. Results 122 faecal samples were collected from 61 subjects. The Mean(SEM) EN intake for the 4 groups was EEN:100(0), CEN:86(0.5), PEN:50(0.4), MEN:20(0.2)% of total energy intake. The baseline levels of all faecal sample measures were no different between the 4 groups. Faecal propionate and BSCS significantly decreased only during EEN (all p≤0.03). Faecal pH significantly increased during EEN, CEN and PEN (all p Conclusions EEN and CEN extensively modulate faecal microbial metabolites. PEN induces variable effects and further analysis should investigate if this variation reflects differences in the non-EN food intake of the participants (50%). MEN had no effect on faecal microbial metabolites. Further analysis including high-throughput deep sequencing techniques will provide additional information about the dose-dependent effect of EN regimen on gut microbiome composition. 1) Quince, Am J Gastroenterol 110, 1718–1729; 2) Logan, APT 50, 664–674, 2019; 3) Gupta, IBD 19, 1374–1378, 2013; 4) Lee, IBD 21, 1786–1793, 2015

Background Exclusive enteral nutrition (EEN) is the recommended first line treatment for active paediatric Crohn’s disease (CD). The mechanism of action and immunological effects of EEN remain unclear. This study compared circulating inflammatory proteins of patients with CD and ulcerative colitis (UC) with non-inflammatory bowel disease (non-IBD) controls and explored the effect of EEN in children with active CD. Methods Patients with CD were treated with EEN for 8 weeks, with plasma samples collected prior to EEN start and upon EEN completion. Levels of 92 inflammatory proteins were quantified using Olink Inflammation panel. Paired faecal samples were collected to measure faecal calprotectin (FC) levels by ELISA. Patients in which FC decreased >50% during EEN were classed as FC responders; whereas patients who had a Results 84 patients were recruited (CD:54, UC:11, non-IBD:19). Paired plasma samples were collected from 18 patients with CD receiving EEN. Of these 18 patients, 72% achieved clinical remission by the end of EEN (wPCDAI Prior to EEN start, 29 proteins were significantly different between patients with CD compared to non-IBD; and 25 proteins were significantly different between UC and non-IBD, Fig 1. EEN lead to the significant alteration of 23 proteins. This included 5 proteins, CCL23, CXCL10, IL6, IL24, and MMP-1 which were higher in patients with CD prior to EEN start compared to non-IBD, Fig 2. In patients who achieved clinical remission during EEN, 22 proteins significantly changed from their EEN start levels by the end of EEN, Fig 3. FC responders had a similar pattern of protein changes, in which 22 proteins changed significantly during EEN, Fig 4. 16/22 (72%) of the proteins that changed significantly in the FC responder group during EEN, also changed during EEN in patients who entered clinical remission including significant reductions in several innate immune proteins such as IL-6 and IL-18. Patients who did not achieve clinical remission did not have significant reductions in these proteins. Despite being higher in patients with CD prior to treatment compared to non-IBD, the level of 17 proteins, including IL17a and oncostatin M, did not change in FC responders during EEN. Conclusion EEN leads to alteration of multiple inflammatory proteins, in keeping with a reduction in innate immune pro-inflammatory activity and improvement in clinical response, although some inflammatory proteins remain elevated. Figure 1: Venn diagram of proteins significantly different Figure 2: Effect of EEN on protein levels Figure 3: Effect of EEN on protein levels, stratified based on clinical response during EEN Figure 4: Effect of EEN on protein levels, stratified based on FC response