Journal of Crohn's & colitis最新文献

{"title":"Impact of type 2 diabetes on clinical outcomes and advanced therapy use in patients with Crohn's disease: a real-world propensity score-matched analysis.","authors":"Sara Massironi, Virginia Solitano, Federica Furfaro, Ferdinando D'Amico, Alessandra Zilli, Mariangela Allocca, Laurent Peyrin-Biroulet, Vipul Jairath, Silvio Danese","doi":"10.1093/ecco-jcc/jjaf157","DOIUrl":"10.1093/ecco-jcc/jjaf157","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) may adversely affect the course and treatment outcomes of Crohn's disease (CD). However, data remain inconsistent.</p><p><strong>Aims: </strong>To evaluate the impact of T2DM on clinical outcomes and advanced therapy use in patients with CD using real-world electronic health record data.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with CD were stratified by the presence of T2DM. Propensity score matching was used to balance demographic and clinical characteristics. Primary outcomes included corticosteroid use, abdominal surgery, drug-related adverse events, and the initiation of advanced therapies. Secondary outcomes included the incidence of neoplasms and mental disorders. Time-to-event outcomes were analyzed using Kaplan-Meier curves and hazard ratios.</p><p><strong>Results: </strong>After matching, 7182 patients were included in each cohort. Corticosteroid use was higher in diabetic patients (61.6% vs 55.2%; P < .001), as were abdominal surgery (32.8% vs 31.1%; P = .010) and drug-related adverse events (4.3% vs 2.4%; P < .001). Use of anti-TNF (10.4% vs 12.2%; P < .001) and IL-23 inhibitors (4.6% vs 5.4%; P = .018) was lower in diabetic patients. Use of vedolizumab (2.4% vs 2.6%; P = .401) and JAK inhibitors (0.6% in both; P = .955) was similar. Neoplasm rates were comparable (3.5% vs 3.2%; P = .386), while mental disorders were more common in the diabetic cohort (51.5% vs 41.2%; P < .001).</p><p><strong>Conclusions: </strong>Patients with CD and coexisting T2DM experience a more severe disease course yet appear to be undertreated with advanced therapies. These findings highlight the need for tailored, multidisciplinary management strategies in this high-risk population.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Day 3 Oxford criteria predict steroid non-response for acute severe ulcerative colitis in the post biologic era.","authors":"Sudheer K Vuyyuru, Lotus Alphonsus, Theshani Amalka De Silva, Virginia Solitano, Leonardo Guizzetti, Terry Ponich, Melanie Beaton, Jamie Gregor, Brian Yan, Michael Sey, Vipul Jairath","doi":"10.1093/ecco-jcc/jjaf131","DOIUrl":"10.1093/ecco-jcc/jjaf131","url":null,"abstract":"<p><strong>Background and aims: </strong>Outcomes of patients admitted with acute severe ulcerative colitis (ASUC) in the post biologic era are under explored, as well as the ability of scoring indices to predict early steroid non-response.</p><p><strong>Methods: </strong>This retrospective cohort study included adults hospitalized with ASUC (2010-2022) at London Health Sciences Centre, Canada. Steroid response, need for rescue therapy, colectomy during index hospitalization, and colectomy and hospitalization at 3- and 12-months following discharge was assessed. Logistic regression identified predictors of steroid non-response, defined as need for rescue therapy or colectomy during hospitalization.</p><p><strong>Results: </strong>Of 261 adults hospitalized with ASUC (male: 51.7%, mean age: 40.6 years), 71.2% had extensive colitis. After intravenous corticosteroid therapy during index admission, 55.7% (n = 147) had a response, 37.9% (n = 99) received rescue therapy (infliximab: 98, tofacitinib: 1, and cyclosporine: 0), and 8% (21/261) underwent colectomy. Additionally, 11.6% (28/240) of patients discharged from hospital underwent colectomy within the first 12 months (8.3% at 3-months and 3.3% between 3 and 12 months). There was no difference between steroid responders and non-responders for colectomy (11% vs 12.6%) or hospitalization (33.5% vs 32.6%) at 12 months. The overall cumulative probabilities of colectomy for the entire cohort at 1 year, 3 years, and 5 years were 13.5%, 16.1%, and 17.4%, respectively. On multivariate analysis, Day 3 Oxford criteria was the only factor found to be statistically significant in predicting steroid non-response (odds ratio 4.70, 95%CI [1.06-20.80]).</p><p><strong>Conclusions: </strong>Day 3 Oxford criteria was an independent predictor of steroid non-response. The risk of colectomy remains substantial after discharge despite low in-hospital colectomy rates following an episode of ASUC. Initial steroid response did not affect long-term colectomy rate at 12 months.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing approach for the discovery of therapeutic agents for Crohn's disease-associated intestinal fibrosis.","authors":"Dimitrios Nikolakis, Andrew Y F Li Yim, Kenneth L Overberg, Mohammed Ghiboub, Manon E Wildenberg, Wouter J de Jonge, Dalia Lartey, Florian Rieder, Geert R D'Haens, Marleen G H van de Sande, Mark Löwenberg","doi":"10.1093/ecco-jcc/jjaf137","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf137","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal fibrosis in Crohn's disease (CD) frequently leads to stricture formation, with current treatment options limited to endoscopic balloon dilation and surgery. This underscores the urgent need for anti-fibrotic therapies. Our objective was to identify therapeutic targets and compounds capable of reversing the fibrotic gene expression profile of mucosal fibroblasts in CD.</p><p><strong>Methods: </strong>We derived a fibrotic gene signature via fibroblasts isolated from stricturing CD tissue and conducted a meta-regression analysis across three publicly available transcriptomic datasets, to identify key differentially expressed genes (DEGs) in fibrostenotic CD. Drug repurposing platforms (iLINCS, L1000, CLUE-io) were implemented to screen compounds with high druggability, for their potential to reverse this pro-fibrotic profile. Transcription factors, microRNAs, and drugs targeting the fibrostenotic signature were identified using the TRRUST, miRWalk, and DGIdb databases, ultimately forming a drug-gene interaction network. The STITCH platform was used to predict compound-protein binding affinities. Promising compounds were subsequently evaluated in vitro, using mucosal fibroblasts derived from fibrostenotic CD patients, and the effect on the expression of selected protein targets was measured via ELISA and immunofluorescence staining.</p><p><strong>Results: </strong>The top upregulated DEGs included fibroblast activation protein (FAP), IL-7 receptor, and transcription factor AP-2 gamma. The drug-gene interaction network analysis identified IL-6 among the most druggable targets. Of 6783 pharmaceutical agents, PI3K inhibitors and histone deacetylase blockers were the most effective in reversing the fibrotic signature via a FAP- and IL-6-dependent mechanism.</p><p><strong>Conclusion: </strong>This integrative approach identified potential anti-fibrotic compounds and molecular targets in CD-associated fibrostenosis, supporting future development of effective therapies.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"19 9","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Novel outcomes in inflammatory bowel disease.","authors":"","doi":"10.1093/ecco-jcc/jjaf117","DOIUrl":"10.1093/ecco-jcc/jjaf117","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"19 9","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmural healing in ulcerative colitis patients improves long-term outcomes compared to endoscopic healing alone.","authors":"Chong-Teik Lim, Christoph Teichert, Maarten Pruijt, Floris De Voogd, Geert D'Haens, Krisztina Gecse","doi":"10.1093/ecco-jcc/jjaf149","DOIUrl":"10.1093/ecco-jcc/jjaf149","url":null,"abstract":"<p><strong>Background & aims: </strong>Endoscopic healing (EH) is recognized as a long-term treatment goal for patients with ulcerative colitis (UC). We investigated whether transmural healing (TH) in UC as assessed by intestinal ultrasound (IUS) is associated with improved outcomes compared to EH alone.</p><p><strong>Methods: </strong>We performed a retrospective study in a tertiary center on patients with left-sided or extensive UC on stable maintenance treatment who had EH [Mayo Endoscopic Subscore (MES) ≤1) and an IUS performed within 6 months of an endoscopy with no treatment alterations between IUS and endoscopy. TH was defined as bowel wall thickness (BWT) <3 mm. The primary outcome was relapse-free survival in patients with and without TH.</p><p><strong>Results: </strong>A total of 61 patients (MES 0: 44.3%; MES 1: 55.7%) with a median follow-up of 20 months were included. On IUS, 72% of patients had TH. Twenty-three patients had a relapse (first-year relapse risk: TH: 7.5% vs no TH: 29.4%, P = .004; MES 0: 3.7% vs MES 1: 20.8%, P = .059). In multivariate Cox regression, female gender [hazard ratio (HR), 2.63; 95% CI 1.05-6.58; P = .039], two or more previous advance therapies (HR, 4.06; 95% CI 1.08-15.28; P = 0.038), and non-TH (HR, 3.99; 95% CI 1.31-12.20; P = .015) were associated with a relapse whereas EH level (MES 0 vs MES 1) was not an associated factor (HR, 1.06; 95% CI 0.32-3.55; P = .924).</p><p><strong>Conclusions: </strong>In UC patients TH is associated with lower relapse risk compared to EH alone. These findings imply that IUS is a non-invasive, low-cost alternative to endoscopy for stratifying UC patients for risk of relapse.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of advanced therapies on surgical recurrence following second ileocolic resection in Crohn's disease.","authors":"Anouck E G Haanappel, Tycho B Moojen, Malaika S Vlug, Roel Hompes, Christianne J Buskens, Willem A Bemelman","doi":"10.1093/ecco-jcc/jjaf156","DOIUrl":"10.1093/ecco-jcc/jjaf156","url":null,"abstract":"<p><strong>Aim: </strong>Long-term outcomes and potential benefits of evolved treatment strategies in patients with Crohn's disease (CD) undergoing a second ileocolic resection (second surgery) are not well characterized. This study aimed to evaluate the risk of a third surgery following second surgery in CD patients.</p><p><strong>Method: </strong>This retrospective cohort study included CD patients undergoing second surgery between 2000-2021 in Amsterdam UMC. Primary outcome was a third surgery due to disease recurrence at the neoterminal ileum. Two cohorts were compared to assess changes over time: C1 (2000-2009) and C2 (2010-2021).</p><p><strong>Results: </strong>In total, 110 patients were included (69 women [62.7%]; median age, 39 years [IQR 30-50]). The rates of third surgery were 12.1% at 5-years and 24.9% at 10-years. Use of prophylactic advanced therapies increased over time (C1: 16.4% vs C2: 41.7%, P = .004). However, the 5-year risk of third surgery was similar in both periods (C1: 12.5% vs C2: 11.5%, P = .45). Similarly, there was no statistically significant difference in third surgery risk between patients treated with vs without prophylactic advanced therapies (HR, 0.87 [95% CI, 0.37-2.02]). Most redo surgeries were performed for stricturing disease, even when the first surgery was for a different indication.</p><p><strong>Conclusion: </strong>Following second surgery, the 5-year third surgery rate is 12.1%, which has remained stable over the past two decades. No statistically significant reduction in third surgery rates were observed in patients receiving prophylactic advanced therapies. This may reflect both the predominantly stricturing disease as indication for redo surgery, which is typically less amenable to medical treatment, and the shorter follow-up in C2.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal Kinase Activity and Inflammatory Profiles in Inflammatory Bowel Disease, and in Relation with Tofacitinib Response.","authors":"Eelco C Brand, Britt Roosenboom, Lisanne Lutter, Bea Malvar Fernandez, Savithri Rangarajan, Elly Van Koolwijk, Sara Van Gennep, Geert R D'Haens, Ellen G Van Lochem, Carmen S Horjus Talabur Horje, Kris A Reedquist, Femke Van Wijk, Bas Oldenburg","doi":"10.1093/ecco-jcc/jjaf174","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf174","url":null,"abstract":"<p><strong>Background & aims: </strong>Not all patients, as with other inflammatory bowel disease (IBD) treatments, respond to modulation of kinase activity. To improve the precision of therapeutic interventions, a better understanding of the mucosal inflammatory environment is essential. This study investigates mucosal kinase activity and cytokine/chemokine profiles in IBD and in relation to tofacitinib response.</p><p><strong>Methods: </strong>Paired inflamed and non-inflamed colonic biopsies were collected from patients with Crohn's disease (CD, N = 16), ulcerative colitis (UC, N = 16), and non-IBD controls (N = 4) to assess IBD-associated kinase activity and cytokine/chemokine profiles. Additionally, colonic samples were collected from UC patients before start of tofacitinib treatment (cohort 1, N = 12) and both before and after 8 weeks of treatment (cohort 2, N = 16), to assess tofacitinib response-related kinase activity profiles.</p><p><strong>Results: </strong>The kinase activity profiles exhibited significant differences between inflamed and non-inflamed mucosa, with more pronounced alterations observed in UC compared to CD. The increase in kinase activity was most pronounced in the tyrosine kinase families. Responders to tofacitinib demonstrated higher baseline mucosal kinase activity, although only two predicted kinases (DCLK1 and ATR) were consistently identified. In responders, mucosal kinase activity significantly decreased after 8 weeks of treatment.</p><p><strong>Conclusion: </strong>Mucosal kinase activity profiles are associated with inflammation in IBD, with distinct differences between UC and CD. Baseline kinase activity appears to predict response to tofacitinib, with a marked reduction in kinase activity observed after 8 weeks of treatment in responders. These findings highlight the potential of kinase activity profiling in optimizing therapeutic strategies for IBD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of Values based healthcare in inflammatory bowel disease-a review article.","authors":"Patrick Hilley, Simone Chin, Darren Wong, Peter De Cruz","doi":"10.1093/ecco-jcc/jjaf173","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf173","url":null,"abstract":"<p><p>The rising global prevalence of inflammatory bowel disease (IBD) and costs of care associated with its management mandates the need to constrain costs whilst improving patient outcomes. Traditional care models such as fee for service do not capture the functional impact of IBD across the whole patient journey. There is a need to develop innovative care models to better address the multifaceted needs of patients with IBD. Values based healthcare(VBHC) is a model of care that aims to deliver quality care by prioritising outcomes that matter to patients in a manner that demonstrates cost-effectiveness of health service provision. In this comprehensive scoping review of the literature, we examine the implementation of VBHC-orientated approaches to IBD care delivery and assess how they have demonstrated value in relation to clinical outcomes, patient reported outcomes (PROs), costs (direct and indirect) and healthcare utilisation (HCU). In addition, we outline key enablers and barriers to implementation of VBHC models in IBD. We then describe the ideal composition of IBD VBHC models and parameters required for implementation and demonstration of their value proposition.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-Life Durability and Risk Factors for Biologic Discontinuation in Pediatric Inflammatory Bowel Disease: Results from the Sigenp IBD Registry.","authors":"Sara Lega, Valeria Dipasquale, Giulia D'arcangelo, Luca Scarallo, Silvana Ancona, Flora Fedele, Giovanna Zuin, Francesco Graziano, Lorenzo Norsa, Simona Gatti, Maria Teresa Illiceto, Enrico Felici, Mara Corpino, Paolo Maria Pavanello, Rita Cozzali, Patrizia Alvisi, Antonio Pizzol, Claudia Banzato, Francesca Penagini, Antonio Marseglia, Simona Faraci, Chiara Luini, Caterina Strisciuglio, Chiara Moretti, Massimo Martinelli, Serena Arrigo, Paolo Lionetti, Marina Aloi, Claudio Romano, Manuela Giangreco, Matteo Bramuzzo","doi":"10.1093/ecco-jcc/jjaf164","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf164","url":null,"abstract":"<p><strong>Background and aims: </strong>This study aims to evaluate the real-life durability of biologic therapies and to identify factors associated with biologic persistence in pediatric inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>We analyzed data from the IBD-registry of the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SIGENP) of patients initiating biologics between 2009-2022 and ≥1-year follow-up.</p><p><strong>Results: </strong>1184 patients (747 with Crohn's Disease [CD], 437 with Ulcerative Colitis or IBD unclassified [UC/IBD-U]) were included, accounting for 1709 treatment courses. The median follow-up was 43 months (IQR 28-64). Overall, 33% received a second-line biologic, 9% third-line, and 2% fourth-line. First-line biologic durability was significantly lower in UC/IBD-U vs. CD, with inferior persistence at 1,2 and 3 years (61%, 51%, and 44% vs 88%, 75%, and 67%; HR 1.5 [95% CI 1.2-1.9], p=.002). In CD, infliximab had inferior durability then adalimumab (72%, 59%, and 50% vs 91%, 82%, and 77%; HR 2.0 [95% CI 1.5-2.7] p < .0001). In both CD and UC/IBD-U, age <6 years was a risk factor for treatment discontinuation (HR 1.8 [95% CI 1.2-2.7], p .01) while therapeutic drug monitoring (TDM) emerged as protective (HR 0.5 [95% CI 0.4-0.7], p <.0001). Combination with an immunomodulator had no significant impact on durability (HR 0.9 [95% CI 0.8-1.2], p = .54).</p><p><strong>Conclusions: </strong>Biologic persistence varied by disease type and biologic agent. TDM was associated with longer treatment durability, while combination therapy had a limited effect. Further prospective studies are needed to refine biologics optimization strategies in pediatric IBD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of prediction models for anti-tumor necrosis factor treatment response in pediatric Crohn's disease: a systematic review and prospective cohort study.","authors":"Omer Rotem-Tryfus, Ben Kang, Esther Orlanski-Meyer, Oren Ledder, Raffi Lev Tzion, Sujin Choi, Byung-Ho Choe, Youra Kang, Dotan Yogev, Ibrahim Shemasne, Muhammed Shawar, Gili Focht, Dan Turner, Ohad Atia","doi":"10.1093/ecco-jcc/jjaf172","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf172","url":null,"abstract":"<p><strong>Background: </strong>External validation of predictors of anti-tumor necrosis factor (TNF) outcomes remains limited, particularly in children. We conducted a systematic review (SR) of the literature to identify predictors of therapeutic success and validated them in a prospective pediatric cohort.</p><p><strong>Methods: </strong>We searched PubMed and Embase for studies reporting clinical and laboratory predictors of anti-TNF outcomes in Crohn's disease (CD). Identified predictors were evaluated in a prospective cohort of 186 children with CD initiating anti-TNF. Univariable logistic regression assessed individual predictors, and previously published multivariable models were validated using the area under the curve (AUC).</p><p><strong>Results: </strong>Of the 4,840 studies screened, 42 were included; 7 (17%) focused on children and only four were rated as low risk of bias. We identified 24 individual predictors and five multi-item models. Of these, prior corticosteroid use (odds ratio [OR], 2.84, 95% CI, 1.12-7.15) and immunomodulator combination therapy (OR 6.36, 95% CI, 2.39-17.10) were associated with increased risk of primary non-response. Disease activity at 4 months, reflected by C-reactive protein and disease activity indices, predicted remission at 12 months. Loss of response was associated with elevated inflammatory markers at 4 months and with partial clinical response. The five multivariable models demonstrated varying performance in children (AUC 0.54-0.76).</p><p><strong>Conclusion: </strong>Only a few of the variables suggested to predict response to anti-TNF showed acceptable performance in pediatric CD, mainly those that included post-induction indicators. These findings highlight the limited generalizability of existing predictors and the importance of external validation before clinical implementation of prediction rules.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}