{"title":"Association Between Biologics and Janus Kinase Inhibitors With Inflammatory Bowel Disease as Paradoxical Reactions: A Real-World Assessment.","authors":"Zhi-Qing Zhan, Jia-Xin Li, Ying-Xuan Chen, Jing-Yuan Fang","doi":"10.1002/ueg2.12719","DOIUrl":"https://doi.org/10.1002/ueg2.12719","url":null,"abstract":"<p><strong>Background and objective: </strong>With limited evidence connecting paradoxical inflammatory bowel disease (paradoxical IBD) to the newest biologics and Janus kinase inhibitors, our study aims to investigate the occurrence of paradoxical IBD induced by these agents in treating other immune-mediated inflammatory diseases (IMIDs). We aim to identify associated risk signals, the primary affected population, and the risk profile changes over time.</p><p><strong>Methods: </strong>We performed disproportionality analysis to evaluate paradoxical IBD risk signals using data from the FDA Adverse Event Reporting System. Stratification analyses according to IBD subtype, age, gender, and agents' indications were performed. Weibull shape parameter (WSP) test was conducted to assess paradoxical IBD risk changes over time. Linkage disequilibrium score regression and Mendelian Randomization were employed to evaluate genetic correlations and causality between these agents' indications (i.e., non-IBD IMIDs) and IBD.</p><p><strong>Results: </strong>This study included 3296 patients reporting 3407 occurrences of paradoxical IBD following using these agents as primary suspects. Among TNF blockers, consistent positive signals for paradoxical IBD were noted: Adalimumab (n = 1983, ROR [95%CI] = 1.55 [1.47-1.63]), Infliximab (n = 545, ROR [95%CI] = 2.12 [1.95-2.32]), Certolizumab Pegol (n = 342, ROR [95%CI] = 1.9 [1.71-2.12]), and Golimumab (n = 154, ROR [95%CI] = 1.64 [1.4-1.93]). Ustekinumab, an IL-12 and IL-23 antagonist, also showed a strong positive signal (n = 155, ROR [95%CI] = 2.03 [1.73-2.39]). Conversely, Upadacitinib, Tofacitinib (Janus kinase inhibitors), and Risankizumab (IL-23 antagonist) exhibited insignificant associations with paradoxical IBD. Crohn's disease (CD) is the mainly developing form. WSP analysis identified two temporal patterns of paradoxical IBD: early failure and random failure types. Significant genetic correlations between three IMIDs and IBD were uncovered, with psoriasis specifically found to causally elevate CD risk.</p><p><strong>Conclusions: </strong>This study identifies paradoxical IBD as a consistent positive signal across multiple IMID agents, predominantly manifesting as CD, potentially aiding in timely detection and therapeutic decision-making.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ioannis Kafetzis, Philipp Sodmann, Bianca-Elena Herghelegiu, Markus Brand, Wolfram G Zoller, Florian Seyfried, Karl-Hermann Fuchs, Alexander Meining, Alexander Hann
{"title":"Prospective Evaluation of Real-Time Artificial Intelligence for the Hill Classification of the Gastroesophageal Junction.","authors":"Ioannis Kafetzis, Philipp Sodmann, Bianca-Elena Herghelegiu, Markus Brand, Wolfram G Zoller, Florian Seyfried, Karl-Hermann Fuchs, Alexander Meining, Alexander Hann","doi":"10.1002/ueg2.12721","DOIUrl":"https://doi.org/10.1002/ueg2.12721","url":null,"abstract":"<p><strong>Background: </strong>Assessment of the gastroesophageal junction (GEJ) is an integral part of gastroscopy; however, the absence of standardized reporting hinders consistency of examination documentation. The Hill classification offers a standardized approach for evaluating the GEJ. This study aims to compare the accuracy of an artificial intelligence (AI) system with that of physicians in classifying the GEJ according to Hill in a prospective, blinded, superiority trial.</p><p><strong>Methods: </strong>Consecutive patients scheduled for gastroscopy with an intact GEJ were recruited during clinical routine from October 2023 to December 2023. Nine physicians (six experienced, three inexperienced) assessed the Hill grade, and the AI system operated in the background in real-time. The gold standard was determined by a majority vote of independent assessments by three expert endoscopists who did not participate in the study. The primary outcome was accuracy. Secondary outcomes were per-Hill grade analysis and result comparison for experienced and inexperienced endoscopists separately.</p><p><strong>Results: </strong>In 131 analysed examinations the AI's accuracy of 84.7% (95% CI: 78.6-90.8) was significantly higher than 62.5% (95% CI: 54.2-71) of physicians (p < 0.01). The AI outperformed physicians in all but one cases in the per-Hill-class analysis. AI was significantly more accurate than inexperienced physicians (85% vs. 56%, p < 0.01) and in trend better than experienced physicians (84% vs. 69.6%, p = 0.07).</p><p><strong>Conclusions: </strong>AI was significantly more accurate than examiners in assessing the Hill classification. This superior model performance can prove beneficial for endoscopists, especially those with limited experience.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT06040723.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ascending the \"Hill\" of Artificial Intelligence in Upper Gastrointestinal Endoscopy.","authors":"Cem Simsek, Nasim Parsa, Lumir Kunovsky","doi":"10.1002/ueg2.12730","DOIUrl":"https://doi.org/10.1002/ueg2.12730","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modifying Our Environment to Improve Outcomes in Inflammatory Bowel Diseases?","authors":"Mathurin Fumery, Nicolas Richard","doi":"10.1002/ueg2.12734","DOIUrl":"https://doi.org/10.1002/ueg2.12734","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multi-Omics Biomarkers for Predicting Efficacy of Biologic and Small-Molecule Therapies in Adults With Inflammatory Bowel Disease: A Systematic Review.","authors":"Liru Chen, Chuhan Zhang, Ruixuan Niu, Shanshan Xiong, Jinshen He, Yu Wang, Pingxin Zhang, Fengyuan Su, Zishan Liu, Longyuan Zhou, Ren Mao, Shixian Hu, Minhu Chen, Yun Qiu, Rui Feng","doi":"10.1002/ueg2.12720","DOIUrl":"https://doi.org/10.1002/ueg2.12720","url":null,"abstract":"<p><p>The heterogeneity and suboptimal efficacy of biological treatments and small molecule drugs necessitate their precise selection based on biomarkers that predict therapeutic responses in inflammatory bowel disease. Recent studies have identified numerous novel biomarkers predictive of responses to biologics and small molecule modulators, utilizing a variety of omics approaches in inflammatory bowel disease. In this review, we systematically examine baseline omics biomarkers that predict responses to biological therapies and small molecule drugs, drawing on literature from PubMed. Our analysis spans multiple omics disciplines, including genomics, transcriptomics (both bulk RNA and single-cell RNA sequencing), proteomics, microbiomics, and metabolomics, with particular emphasis on the impact of models integrating multiple omics datasets. Additionally, to further the field of precision medicine, we evaluated specific biomarkers that may exhibit distinct effects on responses to multiple therapeutic interventions.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D Magalhaes, M Santiago, M Patita, B Arroja, P Lago, I Rosa, H T Sousa, P Ministro, I Mocanu, A Vieira, J Castela, J Moleiro, J Roseira, C Eugenia, P Sousa, F Portela, L Correia, S Dias, J Afonso, S Danese, L Peyrin-Biroulet, C C Dias, F Magro
{"title":"Serum Neutrophil Biomarkers to Predict Crohn's Disease Progression and Infliximab Treatment Outcomes.","authors":"D Magalhaes, M Santiago, M Patita, B Arroja, P Lago, I Rosa, H T Sousa, P Ministro, I Mocanu, A Vieira, J Castela, J Moleiro, J Roseira, C Eugenia, P Sousa, F Portela, L Correia, S Dias, J Afonso, S Danese, L Peyrin-Biroulet, C C Dias, F Magro","doi":"10.1002/ueg2.12712","DOIUrl":"https://doi.org/10.1002/ueg2.12712","url":null,"abstract":"<p><strong>Background and aims: </strong>Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting.</p><p><strong>Methods: </strong>The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin-2, lactoferrin, and resistin (non-neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA.</p><p><strong>Results: </strong>Over up to 2 years of follow-up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin-2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75-0.85); all other correlations were of small magnitude.</p><p><strong>Conclusion: </strong>Our real-world data do not support using serum neutrophil elastase, lipocalin-2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab -treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mucosal Healing in Inflammatory Bowel Diseases: Still Too Many Irons on the Fire. Authors' Reply.","authors":"Tommaso Lorenzo Parigi, Silvio Danese","doi":"10.1002/ueg2.12725","DOIUrl":"https://doi.org/10.1002/ueg2.12725","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"T1 Colorectal Cancer: What Are the Barriers to Minimizing Unnecessary Surgical Interventions?","authors":"Katsuro Ichimasa, Shin-Ei Kudo, Masashi Misawa","doi":"10.1002/ueg2.12729","DOIUrl":"https://doi.org/10.1002/ueg2.12729","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}