Anne M. Griffiths

Objective: To provide an updated, evidence-based European Crohn’s and Colitis Organisation [ECCO]–European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN] guideline for the management, monitoring, and long-term care of pediatric Crohn’s disease [CD]. Methods: A multidisciplinary panel of 27 experts followed ECCO Standard Operating Procedures for guideline development. A systematic review of studies published between January 2018 and October 2024, with targeted updates through June 2025, was conducted across MEDLINE, EMBASE, and Cochrane Central. Evidence was graded using the Oxford Centre for Evidence-Based Medicine levels. Draft statements underwent two Delphi voting rounds involving the guideline panel, ECCO National Representatives, and an international sounding board; statements achieving ≥80% agreement were accepted. Results: This guideline provides updated recommendations across major domains of pediatric CD care, including risk stratification, treatment targets, induction and maintenance strategies, nutritional therapies, therapeutic drug monitoring, and the roles of imaging and endoscopy. High-risk patients should start anti-TNF therapy as first-line treatment, with proactive and reactive therapeutic drug monitoring to enhance efficacy. For low-risk luminal disease, exclusive enteral nutrition or the Crohn’s Disease Exclusion Diet with partial enteral nutrition are preferred induction options. Long-term management emphasizes achieving endoscopic remission, normal growth, improved quality of life, and reduction of bowel damage. This guideline also reviews emerging advanced therapies, including biologics and small molecules, which are increasingly used in practice but generally not yet approved for pediatric CD, to inform clinicians about their potential role. Conclusions: This updated ECCO–ESPGHAN guideline integrates new pediatric evidence with contemporary adult data and treat-to-target principles, providing practical recommendations to support personalized, multidisciplinary, and proactive management aimed at improving long-term outcomes in pediatric CD.

Background: Perianal Crohn’s disease (pCD) is a severe pediatric phenotype with high morbidity. Although antitumor necrosis factor (TNF) agents are first-line therapy, remission is not achieved in a subset of patients. We aimed to evaluate clinical and radiological outcomes of ustekinumab (UST) in pediatric patients with pCD. Methods: This is a multicenter retrospective study including pediatric patients with pCD treated with UST between 2016 and 2023. Primary outcomes were clinical and radiological remission at predefined time points. Clinical remission was defined as absence of fistula drainage without antibiotics or unplanned perianal interventions. Radiological remission was defined as a Pediatric MRI-Based perianal Crohn’s Disease (PEMPAC) score of <10 on pelvic MRI. Results: Fifty patients were included, of whom 2 were anti-TNF-naive. The median age at UST initiation was 15 years (IQR 12.4-16.2). Clinical remission was observed in 46% (23/50; P = .006 vs baseline), 48% (23/48; P = .036 vs baseline), and 42% (19/45; P = .13 vs baseline) at weeks 26, 52, and 104, respectively. Radiological remission was 29% (10/34) and 30% (13/43) at weeks 52 and 104, respectively (both P < .01 vs baseline). In multivariable analysis, higher baseline PEMPAC scores were independently associated with lower odds of both clinical (P < .01; OR 0.88, 95% CI 0.68-0.95) and radiological remission (P < .01; OR 0.81, 95% CI 0.62-0.94). Conclusions: UST was associated with perianal clinical remission in a substantial proportion of pediatric patients, approaching 50% at 1 year, and radiological healing in about one-third at 2 years, supporting its potential role in pediatric pCD.

Adam J Shapiro, Md, Joseph P Castlen, Md, Evans M Machogu, Md, Andrew Tilston-Lunel, PhD, Anne G Griffiths, Md, Benjamin Gaston, Md; Asthma and inhaled cor

Background: UNITI Jr is a phase 3 study evaluating the efficacy, safety, and pharmacokinetics of ustekinumab, an interleukin-12/-23 antagonist, in pediatric patients with moderately to severely active Crohn’s disease. Results from patients weighing at least 40 kg are reported. Methods: Patients at least 40 kg and aged less than 18 years with a Pediatric Crohn’s Disease Activity Index score of >30 received a single intravenous weight-tiered induction dose of ustekinumab. After 8 weeks, patients were randomized to subcutaneous ustekinumab 90 mg every 8 or 12 weeks. The primary endpoint was clinical remission at Week 8. Secondary endpoints included clinical response (Weeks 8, 52), endoscopic response (Weeks 16, 52), clinical remission, and corticosteroid-free remission (Week 52). Results: Of 48 patients, median age was 15.0 years (interquartile range: 14.0-16.0). At Week 8, 52.1% (25/48) achieved clinical remission and 93.8% (45/48) achieved clinical response. At Week 16, 29.8% (14/47) achieved endoscopic response. Clinical remission at Week 52 was achieved in 15/25 (60.0%; every 12 weeks) and 10/23 (43.5%; every 8 weeks). Three patients (6.3%) discontinued ustekinumab between Weeks 8 and 52. Ustekinumab was safe and well-tolerated; adverse event rates were similar between groups. Immunogenicity was low; trough median (mean) steady-state serum ustekinumab concentrations following 8 weeks of dosing were 1.38 (2.08) to 1.74 (2.32) μg/mL and were comparable to levels in adult patients: 2.83 (2.05) μg/mL. Conclusions: Ustekinumab induction and maintenance therapy was effective and safe through 52 weeks in pediatric patients weighing at least 40 kg with moderately to severely active Crohn’s disease. Trial Registration Numbers: NCT04673357

Background: We aimed to build a serum proteomics-based model to predict primary nonresponse (PNR) to infliximab (IFX) in pediatric colonic inflammatory bowel disease, with early proactive therapeutic drug monitoring. Methods: Children in the prospective Canadian Children IBD Network with ulcerative colitis (UC), inflammatory bowel disease unclassified (IBD-U), or colonic Crohn’s disease (CD) with serum pre-IFX were eligible. We defined PNR as IFX cessation plus surgery/drug switch within 6 months. We compared clinical features between groups (Mann Whitney U, chi-square test). We measured serum proteins with Olink Inflammation/Immune Response panels. We built a regularized regression (generalized linear model [GLM]) machine learning model and compared its performance with other models with 10-fold cross-validation repeated 10 times (receiver-operating characteristic/precision-recall curves, predictive score separation). We ranked proteomic features by SHAP (SHapley Additive exPlanations) analysis. We hypothesized that treatment-naïve serum would be more informative than treatment-exposed serum. Results: We included 96 patients: 71 UC/IBD-U (23 nonresponders), 42 treatment-naïve (12 nonresponders); and 25 CD, 19 treatment-naïve. Pre–third and pre–fourth dose serum infliximab levels were similar and robust (>10 µg/mL) in primary nonresponders and responders. Predictive performance was superior for diagnostic, treatment-naïve samples; the GLM showed good ability to separate primary nonresponders and responders. The GLM model on treatment-naïve serum (area under the curve ∼0.75) had better specificity to predict responders and included 21 proteins, with CSF1 and ITM2A top ranked. UC/IBD-U responders more often were steroid refractory and received infliximab as first maintenance. Conclusions: A serum proteomics linear model on treatment-naïve serum best predicted PNR. Findings require external validation but suggest that the diagnostic/pretreatment window may be key to understanding biology central to effective drug sequencing.

Background: Golimumab is an anti-TNFα biologic agent that has been approved for adults with moderately-to-severely active ulcerative colitis (UC). We investigated the efficacy, safety, and pharmacokinetics (PK) of golimumab in biologic-naïve children with moderately-to-severely active UC. Methods: The prospective, multicenter, open-label PURSUIT 2 study enrolled biologic-naïve children (2 to <18 years) with moderately-to-severely active UC (Mayo score 6-12; endoscopic subscore ≥2) despite conventional treatment. During the 6-week induction phase, patients received subcutaneous (SC) golimumab dosed by weight (1) at week 6. Efficacy and PK data are presented alongside a reference adult UC population who received golimumab SC 200/100 mg at weeks 0/2 and 100 mg q4w thereafter. Results: Of the 69 patients (mean age, 13.4 ± 3.3 years) enrolled, 31.9% (22/69) were in clinical remission at week 6, and of those, 54.5% (12/22) remained in clinical remission at week 54. At week 54, 31.7% (13/41) of week 6 clinical responders achieved clinical remission. Additionally, 33.3% achieved clinical remission by the Pediatric Ulcerative Colitis Activity Index (PUCAI), 56.5% clinical response by Mayo, 40.6% endoscopic improvement, and 7.2% endoscopic remission at week 6. Of those who were clinical responders at week 6, 34.1% achieved clinical remission by PUCAI, 31.7% corticosteroid-free clinical remission by Mayo, 36.6% endoscopic improvement, and 9.8% endoscopic remission at week 54. Serum golimumab concentrations through week 6 were comparable to the reference adult UC population. Through week 54, 40.6% reported serious adverse events and 13.0% serious infections. No new safety concerns were identified. Conclusions: Overall, the results of the PURSUIT 2 study support golimumab treatment for children with moderately-to-severely active UC. ClinicalTrials.gov ID: NCT03596645

Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free. In an untargetedassessment of metabolomic data, we identified 63 metabolites significantlyassociated with future CD risk. Integrative analyses further identifiedmultiple associations between CD-related metabolites and proteomic markers, gutmicrobiome composition, antimicrobial antibody, fecal calprotectin andC-reactive protein. Quinolinate, a tryptophan catabolite, was elevated inindividuals who later developed CD and showed strong positive correlations withC-reactive protein, fecal calprotectin, and C-X-C motif chemokine ligand 9 (CXCL9).In contrast, higher levels of ascorbate and isocitrate were associated withreduced CD risk and were negatively correlated with C-reactive protein and CD-associated proteins.These findings identify several distinct molecular pathways that contribute toCD pathogenesis.

Inflammatory bowel diseases (IBD) require effective therapies to prevent morbidity and maintain quality of life. The introduction of biologic agents, beginning with monoclonal antibodies targeting tumor necrosis factor (TNF) alpha, has launched a new era of advancements that have markedly improved short‐ and long‐term outcomes of Crohn's disease and ulcerative colitis. Along with these improvements, there have been challenges to address in optimizing use of biologic therapies in children with IBD. Young children may have rapid drug clearance, and growing children have changing medication needs related to changes in body size, metabolism, and development. For these and other reasons, one size (one dose) does not fit all. Therapeutic drug monitoring (TDM), which involves measurement of drug concentration in serum usually, typically at the predose trough, has emerged as a valuable tool for optimizing dosing and preventing pharmacokinetic failure. This society paper reviews the use of TDM, including target ranges during induction and maintenance therapy for anti‐TNF agents and for emerging biologics. This report has been compiled by pediatric gastroenterologists on behalf of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition IBD committee after extensive review of the current literature. The purpose of this clinical position statement is to provide guidance to clinicians in the use of TDM to optimize the treatment of children with IBD.