Pediatric Inflammatory Bowel Disease Research Articles

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies. To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles. We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior. We employed the model for exposure-response evaluation and for investigating doses in paediatric patients to match the adult exposure at the labelled dose. At Week 30, 104/129 (81%) children (53% female and 47% Crohn disease) remained on vedolizumab, of whom 39 (31%) in the exposure-response evaluation were in deep biochemical remission. Increased baseline drug clearance was associated with lower deep biochemical remission rates at Week 30 based on ESR/CRP (OR 0.47 [95% CI 0.2-1.05, p = 0.08]) and calprotectin < 100 μg/g (OR 0.13 [95% CI 0.1-0.79, p < 0.05]). Higher weight and lower serum albumin were associated with increased clearance (p < 0.001). Simulation models found that, for children ≤ 30 kg, tiered fixed dosing regimens best matched adult drug concentrations. Drug clearance was strongly influenced by serum albumin. Baseline clearance predicted deep biochemical remission at Week 30. Further investigation is needed to better understand optimal dosing strategies-especially for lower-weight children receiving vedolizumab.

Responsiveness and clinical utility of PROMIS instruments in pediatric Crohn's disease: insights from a longitudinal study

BackgroundInflammatory bowel disease (IBD) may adversely affect physical, psychological, and social well-being. Integrating patient-reported outcomes (PROs) into clinical practice is crucial for comprehensive disease management.ObjectiveTo evaluate the responsiveness and clinical utility of Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, compared with standard clinical assessment tools in pediatric CD patients.MethodsA longitudinal, prospective study with 31 pediatric Crohn's disease (CD) patients aged 8–17 years recruited from a Pediatric Gastroenterology Unit. Data were collected at baseline and every 6 months over 18 months. PROMIS pediatric measures assessed PROs. Disease activity was evaluated using the pediatric Crohn's disease activity index (PCDAI) and clinical markers. IMPACT-III was also applied. Linear mixed-effects models (LMMs) and bivariate analyses were used to assess changes over time.ResultsPROMIS Global Health scores showed significant improvement over time, indicating enhanced overall health perceptions among patients. Notable reductions were observed in PROMIS Pain Interference and Fatigue scores, indicating better physical health. PROMIS depression scores generally decreased, suggesting improved mental health. PCDAI scores, hemoglobin, and platelet count significantly changed and correlated with PROMIS measures. Globally, the study demonstrated significant and clinically relevant changes in multiple PROMIS measures, confirming their responsiveness to changes in disease activity.ConclusionPROMIS instruments are clinically useful in managing pediatric CD, providing valuable insights into global health and quality of life. Integrating PROMIS measures into routine clinical practice may enhance disease management and treatment strategies for pediatric IBD patients.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking. We assessed the therapeutic response to help close this gap. This retrospective study involved 30 sites worldwide. Demographic, clinical, and laboratory data were collected from patients with VEO-IBD who commenced adalimumab therapy before the age of 6 years. Seventy-eight patients (37 Crohn's disease, 26 ulcerative colitis, and 15 with IBD-unclassified) were included. Median age of IBD onset was 2.6 (1.3-4.1) years, with 30 (38.5%) patients diagnosed at age <2 years. Median age at adalimumab initiation was 4.2 (2.8-5.1) years. Adalimumab was used as second-line biologic therapy in 45 (57.7%) patients after infliximab. The median time to last follow-up was 63 (22-124) weeks. Significant improvement in clinical scores, CRP, fecal calprotectin, and weight Z-score were observed by Week 52. Adalimumab durability rates were 61.9%, 48.1%, and 35.6% after 1, 2, and 3 years, respectively. Drug discontinuation rates were not dependent on IBD type, age, prior anti-TNF exposure, or concomitant immunomodulatory treatment. Four (5.1%) patients developed serious infections, including 1 patient with TTC7A deficiency who died following adenovirus sepsis. Adalimumab therapy is a viable therapeutic option in patients with VEO-IBD with an acceptable safety profile.

Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs

Background: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX. This study aims to examine the relationship between the HLA-DQA1*05 variant and response loss or antibody development in patients regularly monitored on IFX or ADA. Methods: Sixty-five paediatric IBD patients were enrolled, with therapeutic drug monitoring (TDM) of IFX and ADA, conducted using immunoenzymatic assays. The presence of the HLA-DQA1*05 T&gt;C allele variant was also tested using a Biomole HLA-DQA1 Real-time PCR kit. Results: The HLA-DQA1*05 rs2097432 T&gt;C allele was present in 54% of patients on IFX and 69% of those on ADA. No statistically significant differences were found between HLA carriers and non-carriers across any of the three analysed groups: IFX, ADA and the overall anti-TNFα. Conclusions: Our study suggests that the HLA-DQA1*05 allele does not increase the risk of secondary loss of response to anti-TNF therapy, likely because most patients were on a combination of anti-TNF agents and immunomodulators, which can lower anti-drug antibody production. Testing for HLA-DQA105 can aid in personalising treatment and optimising therapy to minimise immunogenicity risks.

Anti-Tumor Necrosis Factor-α Use in Pediatric Inflammatory Bowel Disease—Reports from a Romanian Center

Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies. Methods: This retrospective, single-center study examined pediatric IBD patients receiving anti-TNF-α therapy at the “Grigore Alexandrescu” Emergency Hospital for Children in Bucharest, Romania, from January 2015 to October 2024. AEs were categorized into non-infectious complications (acute infusion reactions, anti-drug antibody formation), dermatological effects (erythema nodosum, vasculitis), neurological effects (Guillain–Barré syndrome), and infections. AEs were analyzed in relation to the specific anti-TNF-α agent administered and comprehensively characterized. Results: Of 40 patients enrolled, 22 (55%) had Crohn’s disease (CD). The median (IQR) age at diagnosis was 14.8 years [10.8–15.9]. IFX was used in 34 (85%) patients while 6 (15%) patients received either ADA or IFX/ADA sequential therapy. Twenty-seven AEs were documented in 19 (47.5%) patients, the most prevalent being antidrug antibody formation (44.4%), infections (22.2%), and acute infusion reactions (22.2%). All ADA-exposed patients experienced at least one AE, compared to 41.2% (n = 14) patients treated with IFX, p = 0.01. Conclusions: AEs were observed in approximately half of the study cohort, with anti-drug antibody formation emerging as the most frequent complication. ADA therapy was associated with a significantly higher rate of AEs compared to IFX. These findings underscore the critical importance of vigilant monitoring for patients undergoing anti-TNF-α therapy in pediatric IBD management.

Link between Pediatric Inflammatory Bowel Disease and Growth Retardation: A Systematic Review

The main objective of this study was to underlie the growth impairment mechanisms in pediatric inflammatory bowel disease (IBD) patients. A total of 584 pertinent publications were found after a comprehensive search across four databases. Full-text publications (293) were examined after duplicates were eliminated using Rayyan QCRI and relevance was checked; seven studies finally satisfied the requirements for inclusion. A total of 1927 children diagnosed with IBD were included in this research; 1467 with Crohn's disease (CD) and 460 with ulcerative colitis (UC). Males were 1153 (59.5%). Growth abnormalities, especially in CD patients, are commonly observed in children with IBD, often appearing strongly before age fifteen. These growth issues, including height and weight retardation, are worsened by chronic inflammation and are particularly severe in children with low weight at diagnosis. Younger children, particularly those under ten, are more affected than older children, especially in cases of UC. Adolescents with IBD may also experience disruptions in the pubertal growth spurt, possibly due to hormonal imbalances, such as reduced insulin-like growth factor-1 (IGF-1) availability. Pediatric IBD is closely linked to growth issues, especially in children with CD and those diagnosed at a young age. Early diagnosis and proper management are essential to support normal growth and prevent long-term effects. Clinicians should monitor growth as a key indicator of disease impact and provide nutritional and medical support. Further researches are needed to identify the best strategies to address growth problems and help these children reach their full potential.

Anthropometric Trajectories in Children Prior to Development of Inflammatory Bowel Disease

Poor nutrition and growth in childhood have short-term and long-term consequences, so understanding the timing of the onset of an impaired nutritional status is crucial for diagnosing and treating inflammatory bowel disease (IBD) at its earliest stage. To assess anthropometric trajectories before a pediatric diagnosis of IBD and growth recovery after diagnosis. This population-based cohort study included children born in Denmark from January 1, 1997, through December 31, 2015, with weight and length or height measurements at birth and at least 1 length or height and weight measurement at school age based on the Danish Medical Birth Register and the Danish National Child Health Register. Within this population, all individuals diagnosed with IBD at ages 5 to 17 years, according to the Danish National Patient Register, were identified. Data were analyzed from October 13, 2023, to April 17, 2024. A pediatric diagnosis of IBD compared with the corresponding population without the disease. The outcome measures were z scores for length or height, weight, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) before and after pediatric IBD diagnosis compared with reference and sibling populations. The final study population included 916 133 individuals (51.2% male) with a median of 3 pairs of length or height and weight measurements collected (IQR, 2-6 pairs). Of those, 1522 (median age, 14.3 years [IQR, 11.8-16.3 years]; 763 female [50.1%]) were diagnosed with IBD (851 [55.9%] with Crohn disease [CD] and 671 [44.1%] with ulcerative colitis [UC]). Compared with children without IBD, individuals with a later diagnosis of CD had declining anthropometric measures 3 years (weight: mean, -0.12 g [95% CI, -0.20 to -0.03 g]; BMI: mean, -0.13 [95% CI, -0.21 to -0.04]) and 1 year (length or height: mean, -0.20 cm [95% CI, -0.29 to -0.10 cm]) prior to diagnosis, whereas this was observed 1 year prior to a diagnosis of UC for weight (mean, -0.12 g [95% CI, -0.22 to -0.02 g]) and BMI (mean, -0.13 [95% CI, -0.23 to -0.03]). Deviating anthropometric patterns persisted after diagnosis, with the slowest recovery observed in children with CD. The findings of this large-scale population-based cohort study of anthropometrics in children suggest impaired nutritional status as assessed by weight up to 3 years and by length or height 1 year before a diagnosis of CD and by weight up to 1 year before a diagnosis of UC. These findings emphasize that the onset of pediatric IBD may occur years prior to diagnosis, that growth recovery may first occur after diagnosis and treatment, and that frequent nutritional screenings may help ensure a healthy transition to adulthood.

Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study.

Infliximab and adalimumab are the only biologics thus far approved for paediatric patients with inflammatory bowel disease (IBD), so other biologics, such as vedolizumab, are prescribed off-label. Despite its frequent use, prospective data for vedolizumab treatment in children are available only for short-term induction outcomes. We aimed to evaluate the long-term efficacy and safety of maintenance therapy with vedolizumab in paediatric patients with IBD. In this multicentre, prospective, cohort study (VEDOKIDS), children younger than 18 years with Crohn's disease, ulcerative colitis, or IBD unclassified (analysed with the ulcerative colitis group) who had initiated intravenous vedolizumab were enrolled from 17 centres in six countries (Israel, the USA, Italy, Ireland, Denmark, and Slovenia). Patients initiating vedolizumab to prevent postoperative recurrence were excluded. Vedolizumab dose or schedule were not standardised, and concomitant treatment with any other medication was permitted. Patients were prospectively followed up for 54 weeks, with repeated biosampling. The primary outcome was complete remission at week 54, defined as clinical remission (weighted Paediatric Crohn's Disease Activity Index [wPCDAI] of <12·5 points in Crohn's disease and Paediatric Ulcerative Colitis Activity Index [PUCAI] of <10 in ulcerative colitis) without the need for surgery, exclusive enteral nutrition for children with Crohn's disease, or steroids (steroid-free and exclusive enteral nutrition-free clinical remission) plus CRP concentration lower than 1·5 times the upper limit of normal (ULN) of 0·5 mg/dL. In cases of missing data on CRP, ESR was used instead (concentrations <1·5 times the ULN, which was 25 mm/h). Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT02862132. Between May 19, 2016, and April 1, 2022, we enrolled 142 patients. Five children who had received only one or two infusions of their three-infusion induction before switching drugs due to COVID-19 pandemic-related reasons were excluded, leaving 137 children (64 [47%] with Crohn's disease, 64 [47%] with ulcerative colitis, and nine [7%] with IBD unclassified; 63 [46%] male and 74 [54%] female; age range of 0·7-17·6 years) in the intention-to-treat population. The median wPCDAI score in children with Crohn's disease decreased from 35 (IQR 18 to 49) at baseline to 13 (0 to 25; median of differences -14 [95% CI -33 to 0]) at week 54, and the median PUCAI score in children with ulcerative colitis decreased from 25 (IQR 15 to 50) at baseline to 5 (0 to 25) at week 54 (median of difference -10 [-30 to 0]). Improvements in disease activity were significant by week 6, with no further significant changes between visits. At week 54, 16 (25%) of 64 children with Crohn's disease and 34 (47%) of 73 with ulcerative colitis or IBD unclassified were in complete remission. 38 vedolizumab-related adverse events were recorded in 29 (21%) of 137 children, the most common being headache (n=7), myalgia (n=4), and fever (n=4), and none were serious. Vedolizumab maintenance seems safe and efficacious in children, with a higher efficacy in those with ulcerative colitis than in those with Crohn's disease. The European Crohn's and Colitis Organisation, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

Intestinal Goblet Cell-Expressed Reg4 Ameliorates Intestinal Inflammation Potentially by Restraining Pathogenic Escherichia coli Infection.

An elevated abundance of Escherichia coli (E. coli) has been linked to the onset and progression of inflammatory bowel disease (IBD). Regenerating islet-derived family member 4 (Reg4) has been isolated from patients with ulcerative colitis (UC), but its functions and involved mechanisms in intestinal inflammation are remain incompletely understood. Therefore, we generated an intestinal conditional Reg4 knockout mouse (Reg4ΔIEC) to address this gap by utilizing murine models of enteropathogenic E. coli (EPEC)-infected bowel and dextran sulfate sodium (DSS)-induced colitis. We here demonstrate that REG4 is increased in diseased intestinal mucosa of pediatric IBD, primarily expressed and enriched in intestinal goblet cells. Deficiency of Reg4 in the intestinal epithelium of mice leads to an increase in the Phylum Proteobacteria and in the family Enterobacteriaceae. Administration of recombinant Reg4 protein significantly mitigates EPEC-induced intestinal inflammation and injury in a murine model. In vitro, Reg4 protein suppresses the growth and motility of EPEC, subsequently reducing their adhesion and invasion to the intestinal epithelial cells. Mechanistically, the conserved mannan-binding sites (like C-lectin domain) are essential for Reg4 antimicrobial activity. Moreover, loss of Reg4 in mice increases susceptibility to DSS-induced colitis, which can be improved by gentamicin (GM), an antibiotic for Gram-negative bacteria. In conclusion, intestinal goblet cell-derived Reg4 is crucial for protection against experimental colitis, likely due to its bactericidal activity against EPEC.

Publication bias in studies on biologic therapy for children with inflammatory bowel disease.

The utilization of biologic drugs in children with inflammatory bowel disease (IBD) surged following the publications of positive results in randomized controlled trials and real-world studies. We aimed to explore the extent of publication bias associated with these findings. Two reviewers assessed all abstracts evaluating the efficacy or safety of biologics presented at the annual European Society for Pediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology conferences from 2015 to 2019. Abstracts were classified as "positive" or "negative." Time to publication was analyzed using Kaplan-Meier curve and groups were compared using the log-rank test. A Cox proportional model was utilized to determine the likelihood of publication. Out of 209 included abstracts, only 130 (62%) were published as full manuscripts. The median time to publication was 2.8 years (interquartile range = 0-8.2). In the univariate Cox model, the likelihood of publication was four times higher for abstracts reporting positive results (hazard ratio = 4.4 [95% confidence interval, CI = 2.3-8.5]). The probabilities for publication at 1, 3, and 5 years after the conference were 32%, 59%, and 66% for abstracts with significantly positive results in favor of biologic treatment compared to 10%, 22%, and 25% for those with negative results (p < 0.001). In multivariable model, positive results (odds ratio = 6.4 [95% CI = 2.5-16.4]) were significant associated with publication rate. Only 62% of abstracts presented in medical conferences regarding biologics in pediatric IBD are eventually published as full manuscripts, and those reporting positive results were more likely to be published and at an earlier time. Clinicians, guideline groups, and medical authorities dealing with drug approval, need to be aware of potential publication bias of published studies when employing evidence-based management strategies.

Long-Term Effectiveness and Safety of Proactive Therapeutic Drug Monitoring of Infliximab in Paediatric Inflammatory Bowel Disease: A Real-World Study.

This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM. Of the 38 patients, 21 had Crohn's disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients.

A decade of real-world clinical experience with 8-week azithromycin-metronidazole combined therapy in paediatric Crohn's disease.

The aim of our study was to assess the effectiveness and side-effect profile of a combination of azithromycin and metronidazole (CD AZCRO) as alternative induction therapy for 8 weeks in mild to moderately active paediatric Crohn's disease (CD). We performed a retrospective cohort study (November 2012 to July 2023) of a regional paediatric inflammatory bowel disease service. Disease activity, faecal calprotectin (FC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), haematological parameters and albumin were collected at baseline, 8 and 16 weeks. At Week 8, patients were divided based on (paediatric Crohn's disease activity index) score and inflammatory markers (blood and stool) into: group 1 clinical remission and group 2 non-remission. A total of 48 patients were initially identified of whom 44 were included in the intention-to-treat analysis. After 8 weeks, the overall remission rate was 64%. Of the 38 patients who completed the CD AZCRO course, 28 patients (74%) entered remission (group 1) and 10 (26%) did not (group 2). At baseline a shorter disease duration, low weight z score and higher inflammatory burden (ESR, platelets and FC levels) were observed in group 2. After 8 weeks, group 1 showed improved CRP levels and higher albumin and haemoglobin levels than group 2. Median FC declined significantly from 650 mcg/g at baseline to 190 mcg/g at Week 8 in group 1 (p < 0.001). At 16 weeks, 23/28 patients (82%) continued in clinical remission. Nausea and vomiting were reported in 4/44 patients. Our real-world data demonstrate that CD AZCRO represents an alternative induction therapy for mild to moderate paediatric CD.

Patient-Reported Outcomes Measurement Information System as a Clinical Tool for Capturing the Patient Perspective in Pediatric Inflammatory Bowel Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is an immune-mediated chronic disease with a significant impact on quality of life. In pediatric patients, diagnosing and managing IBD is particularly challenging, and IBD often presents as a more severe and progressive disease. Patient-reported outcomes (PROs) are measures of treatment and disease management outcomes reported by patients and/or caregivers. These measures evaluate several aspects of disease management from the patient/caregiver perspective, emphasizing the patient's real-life experience with the disease and its treatment. PROs represent a model of patient-centered care, facilitating better-informed healthcare decisions. The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to promote the use of PROs among patients with chronic conditions. Its primary objective is to provide PROs for research and clinical practice throughout the lifespan. The PROMIS is a non-disease-specific instrument for both adults and pediatric patients assessing domains of physical, psychological, and social health, as well as quality of life (QOL). These instruments are designed to be applicable to a wide range of chronic diseases. Despite the initial expectation concerning PROs in assessing pediatric IBD outcomes, objective data in this area have only recently begun to emerge. This narrative review, based on a selection of reliable articles recognized by PubMed and Cochrane Library, aimed to identify and summarize previously published evidence of the usefulness of PROs, particularly the PROMIS, in IBD patients and in the pediatric population. We present an updated perspective, including identification of their general applications and most relevant previous studies, in the mentioned areas and identify knowledge gaps.

Editorial: The safety and efficacy of ustekinumab in anti-TNFα refractory pediatric inflammatory bowel disease.

Editorial: The safety and efficacy of ustekinumab in anti-TNFα refractory pediatric inflammatory bowel disease.

Characteristics of the gut microbiota and the effect of Bifidobacterium in very early-onset inflammatory bowel disease patients with IL10RA mutations.

Very early-onset inflammatory bowel disease (VEO-IBD) is a distinct subtype of inflammatory bowel disease (IBD) characterized by onset before the age of 6 years, and patients often exhibit more severe clinical features. Interleukin 10 receptor alpha (IL10RA) is a hotspot mutation in the Chinese population and is associated with a poor prognosis closely linked to the onset of IBD. However, limited knowledge exists regarding how the IL10RA mutation influences the host microbiota and its role in disease development. We employed 16S rRNA sequencing to conduct a comprehensive assessment of microbial changes in different types of IBD, employed database to thoroughly examine the influence of Bifidobacterium in IBD and to demonstrate a potential positive effect exerted by Bifidobacterium breve M16V (M16V) through a mouse model. The study demonstrated a significant reduction in the abundance and diversity of the gut microbiota among children with IL10RA mutations compared to those with late-onset pediatric IBD and nonmutated VEO-IBD. Furthermore, the analysis identified genera capable of distinguishing between various types of IBD, with the genus Bifidobacterium emerging as a potential standalone diagnostic indicator and Bifidobacterium may also be involved in related pathways that influence the progression of IBD, such as the biosynthesis of amino acids and inflammation-related pathways. This study corroborated the efficacy of Bifidobacterium in alleviating intestinal inflammation. The impact of IL10RA mutations on VEO-IBD may be mediated by alterations in microbes. M16V demonstrates efficacy in alleviating colitis and holds promise as a novel microbial therapy.

Cross-cultural adaptation and validation of Work Productivity and Activity Impairment questionnaires for caregivers of patients with pediatric inflammatory bowel disease in Spain. A multicenter study.

Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.

S63 Assessing Attitudes, Access, Barriers, and Facilitators to Multidisciplinary Care in Pediatric Inflammatory Bowel Disease

S63 Assessing Attitudes, Access, Barriers, and Facilitators to Multidisciplinary Care in Pediatric Inflammatory Bowel Disease

S55 Ironing Out the Efficacy and Safety Profile of Ferric Carboxymaltose Infusions for the Treatment of Iron Deficiency and Iron-Deficiency Anemia in Pediatric Inflammatory Bowel Disease

S55 Ironing Out the Efficacy and Safety Profile of Ferric Carboxymaltose Infusions for the Treatment of Iron Deficiency and Iron-Deficiency Anemia in Pediatric Inflammatory Bowel Disease

S78 Rapid Versus Standard Infliximab and Infliximab Biosimilar Infusions in Pediatric Inflammatory Bowel Disease: Comparison of Adverse Reactions

S78 Rapid Versus Standard Infliximab and Infliximab Biosimilar Infusions in Pediatric Inflammatory Bowel Disease: Comparison of Adverse Reactions

S40 Infliximab Biosimilars in Pediatric Inflammatory Bowel Disease: Comparison and Adverse Effects

S40 Infliximab Biosimilars in Pediatric Inflammatory Bowel Disease: Comparison and Adverse Effects