New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.
This narrative review examines emerging therapeutic strategies for four major pediatric gastroenterological conditions: celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH). For CeD, the authors discuss gluten-degrading enzymes (latiglutenase, Kuma030), the zonulin inhibitor larazotide acetate, transglutaminase 2 inhibitors (ZED-1227), and monoclonal antibodies such as AMG 714, noting inconsistent clinical outcomes and limited pediatric data. For EoE, biologics including dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), mepolizumab, reslizumab, benralizumab (IL-5/IL-5R inhibitors), and the TSLP inhibitor tezepelumab are reviewed with varying reported efficacy. IBD coverage includes biologics (vedolizumab, ustekinumab, risankizumab) and small molecules (tofacitinib, etrasimod, upadacitinib), alongside personalized approaches integrating therapeutic drug monitoring. Emerging AIH therapies for refractory or steroid-dependent cases are also explored. The authors highlight proteomics and precision medicine as growing tools to individualize care. A key limitation is the narrative design, which is subject to selection bias, and the scarcity of pediatric-specific trial data across all discussed treatments.
Why this grade: This is a narrative review synthesizing existing literature without systematic methodology or meta-analysis, so it does not independently generate primary clinical evidence.
Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.
Educational summary of published research — not medical advice. License: cc by. Full text is shown only where licensing permits.