Bobby Lo, Luc Biederman, Gerhard Rogler, Barbara Dora, Andrea Kreienbühl, Ida Vind, Flemming Bendtsen, Johan Burisch
{"title":"Specific Antibiotics Increase the Risk of Flare-Ups in Patients with Inflammatory Bowel Disease: Results from a Danish Nationwide Population-Based Nested Case-Control Study.","authors":"Bobby Lo, Luc Biederman, Gerhard Rogler, Barbara Dora, Andrea Kreienbühl, Ida Vind, Flemming Bendtsen, Johan Burisch","doi":"10.1093/ecco-jcc/jjae027","DOIUrl":"10.1093/ecco-jcc/jjae027","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease [IBD] patients have a relapsing-remitting disease course, and amongst environmental factors that aggravate the disease course, common drugs aside from non-steroidal anti-inflammatory drugs have not been studied in detail. While the microbiome is considered to play a significant role on the disease course, the impact of antibiotics is poorly understood. This study investigated the potential impact of different classes of antibiotics on the course of disease in IBD using the Danish National Patient Registry.</p><p><strong>Methods: </strong>Danish IBD patients were studied using two nested case-control cohorts exploring associations between antibiotic types and IBD flare-ups, defined as IBD-related hospitalizations and/or high-dose systemic steroid exposure. Multivariate logistic regression and eXtreme Gradient Boosted decision tree [GBDT] machine learning methods evaluated antibiotic risks.</p><p><strong>Results: </strong>Two cohorts with 15 636 and 5178 patients were analysed for risk of hospitalization and course of steroids, respectively. The risk of a flare-up was significantly increased with antecedent exposure to quinolones (ATC:J01M; odds ratio [OR]: 3.04-3.82), antimycotics [ATC:J02A; OR: 1.50-2.30], agents against amoebiasis and protozoal infections [ATC:P01A; OR: 1.95-3.18], intestinal anti-infectives [ATC:A07A; OR: 2.09-2.32], and beta-lactam antibiotics [ATC:J01C; OR: 1.36]. The GBDT models achieved an area under the curve of 0.71-0.85 for predicting flare-ups, with the same above-mentioned antibiotics being in the ten most important variables.</p><p><strong>Conclusion: </strong>We found distinctive antibiotics to be significantly associated with an increased risk of IBD flare-ups. Our findings are corroborated by our GBDT machine learning models. Healthcare providers should be aware of the deleterious potential of specific antibiotic groups in patients with IBD only using these agents in a restrictive manner or preferentially consider alternative antibiotic groups.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898406","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}
Zhijun Geng, Jing Li, Lugen Zuo, Xiaofeng Zhang, Lian Wang, Yongsheng Xia, Jingjing Yang, Lixia Yin, Xue Song, Yueyue Wang, Damin Chai, Min Deng, Yuanyuan Ge, Rong Wu, Jianguo Hu
{"title":"Intestinal Adipocytes Transdifferentiate into Myofibroblast-like Cells and Contribute to Fibrosis in Crohn's Disease.","authors":"Zhijun Geng, Jing Li, Lugen Zuo, Xiaofeng Zhang, Lian Wang, Yongsheng Xia, Jingjing Yang, Lixia Yin, Xue Song, Yueyue Wang, Damin Chai, Min Deng, Yuanyuan Ge, Rong Wu, Jianguo Hu","doi":"10.1093/ecco-jcc/jjae036","DOIUrl":"10.1093/ecco-jcc/jjae036","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD.</p><p><strong>Methods: </strong>The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-β signalling was also studied to explore the underlying mechanism.</p><p><strong>Results: </strong>Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. Lipopolysaccharide [LPS]-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-β signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue.</p><p><strong>Conclusions: </strong>Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-β signalling.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095424","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}
Malte Lehmann, Benjamin Weixler, Sefer Elezkurtaj, Christopher Loddenkemper, Anja A Kühl, Britta Siegmund
{"title":"Spatial Single Cell Profiling Using Imaging Mass Cytometry: Inflammatory Versus Penetrating Crohn's Disease.","authors":"Malte Lehmann, Benjamin Weixler, Sefer Elezkurtaj, Christopher Loddenkemper, Anja A Kühl, Britta Siegmund","doi":"10.1093/ecco-jcc/jjae033","DOIUrl":"10.1093/ecco-jcc/jjae033","url":null,"abstract":"<p><strong>Background and aims: </strong>Fistula formation is a major complication in Crohn's disease [CD] and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry [IMC] and immunofluorescence.</p><p><strong>Methods: </strong>A 36-marker panel including structural, functional, and lineage markers for use in IMC was established. This panel was applied to analyse paraffin-embedded CD fistula tract [n = 11], CD colitis [n = 10], and colon samples from non-inflamed controls [n = 12]. Computational methods for cell segmentation, dimensionality reduction, and cell type clustering were used to define cell populations for cell frequency, marker distribution, and spatial neighbourhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis.</p><p><strong>Results: </strong>Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells, and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 [MMP9], correlating with extracellular matrix remodelling. Neighbourhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis.</p><p><strong>Conclusions: </strong>This study presents the first highly multiplexed single cell analysis of the immune cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodelling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095426","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}
Shafquat Zaman, Ali Yasen Y Mohamedahmed, Widad Abdelrahman, Hashim E Abdalla, Ali Ahmed Wuheb, Mohamed Talaat Issa, Nameer Faiz, Nuha A Yassin
{"title":"Minimally Invasive Surgery for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Robotic Versus Laparoscopic Surgical Techniques.","authors":"Shafquat Zaman, Ali Yasen Y Mohamedahmed, Widad Abdelrahman, Hashim E Abdalla, Ali Ahmed Wuheb, Mohamed Talaat Issa, Nameer Faiz, Nuha A Yassin","doi":"10.1093/ecco-jcc/jjae037","DOIUrl":"10.1093/ecco-jcc/jjae037","url":null,"abstract":"<p><strong>Background: </strong>We aimed to evaluate outcomes of robotic versus conventional laparoscopic colorectal resections in patients with inflammatory bowel disease [IBD].</p><p><strong>Methods: </strong>Comparative studies of robotic versus laparoscopic colorectal resections in patients with IBD were included. The primary outcome was total post-operative complication rate. Secondary outcomes included operative time, conversion to open surgery, anastomotic leaks, intra-abdominal abscess formation, ileus occurrence, surgical site infection, re-operation, re-admission rate, length of hospital stay, and 30-day mortality. Combined overall effect sizes were calculated using a random-effects model and the Newcastle-Ottawa Scale was used to assess risk of bias.</p><p><strong>Results: </strong>Eleven non-randomized studies [n = 5566 patients] divided between those undergoing robotic [n = 365] and conventional laparoscopic [n = 5201] surgery were included. Robotic platforms were associated with a significantly lower overall post-operative complication rate compared with laparoscopic surgery [p = 0.03]. Laparoscopic surgery was associated with a significantly shorter operative time [p = 0.00001]. No difference was found in conversion rates to open surgery [p = 0.15], anastomotic leaks [p = 0.84], abscess formation [p = 0.21], paralytic ileus [p = 0.06], surgical site infections [p = 0.78], re-operation [p = 0.26], re-admission rate [p = 0.48], and 30-day mortality [p = 1.00] between the groups. Length of hospital stay was shorter following a robotic sub-total colectomy compared with conventional laparoscopy [p = 0.03].</p><p><strong>Conclusion: </strong>Outcomes in the surgical management of IBD are comparable between traditional laparoscopic techniques and robotic-assisted minimally invasive surgery, demonstrating the safety and feasibility of robotic platforms. Larger studies investigating the use of robotic technology in Crohn's disease and ulcerative colitis separately may be of benefit with a specific focus on important IBD-related metrics.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095425","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}
Phoebe Hodges, Oluwafunmilayo Adeniyi, Smita Devani, Chinenye Nwoko, Opeyemi Owoseni, Kwadwo Gyebi Agyenim Boateng, Anthony Ocanit, Abdallah Muhofa, Nasiru Altine Dankiri, Babatunde Duduyemi, Zenahebezu Abay, Yusuf Musa, Eileen Micah, Pissi Kabagambe, Abate Bane Shewaye, Preetha Thomas, Samuel Wanjara, David Epstein, Gillian Watermeyer, Hani Fathi, Olusegun Alatise, Mzamo Mbelle, Paul Kelly, Nick Croft
{"title":"Emerging patterns of inflammatory bowel disease in sub-Saharan Africa: 175 cases from an IBD network.","authors":"Phoebe Hodges, Oluwafunmilayo Adeniyi, Smita Devani, Chinenye Nwoko, Opeyemi Owoseni, Kwadwo Gyebi Agyenim Boateng, Anthony Ocanit, Abdallah Muhofa, Nasiru Altine Dankiri, Babatunde Duduyemi, Zenahebezu Abay, Yusuf Musa, Eileen Micah, Pissi Kabagambe, Abate Bane Shewaye, Preetha Thomas, Samuel Wanjara, David Epstein, Gillian Watermeyer, Hani Fathi, Olusegun Alatise, Mzamo Mbelle, Paul Kelly, Nick Croft","doi":"10.1093/ecco-jcc/jjae126","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae126","url":null,"abstract":"<p><p>There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here we report a series of 175 cases from 12 countries over 2 years.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977509","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}
Massimo Claudio Fantini, Gionata Fiorino, Agostino Colli, David Laharie, Alessandro Armuzzi, Flavio Andrea Caprioli, Javier P Gisbert, Julien Kirchgesner, Fabio Salvatore Macaluso, Fernando Magro, Subrata Ghosh
{"title":"Pragmatic Trial Design to Compare Real-world Effectiveness of Different Treatments for Inflammatory Bowel Diseases: The PRACTICE-IBD European Consensus.","authors":"Massimo Claudio Fantini, Gionata Fiorino, Agostino Colli, David Laharie, Alessandro Armuzzi, Flavio Andrea Caprioli, Javier P Gisbert, Julien Kirchgesner, Fabio Salvatore Macaluso, Fernando Magro, Subrata Ghosh","doi":"10.1093/ecco-jcc/jjae026","DOIUrl":"10.1093/ecco-jcc/jjae026","url":null,"abstract":"<p><strong>Background and aims: </strong>Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The European consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid, comparative, pragmatic studies in inflammatory bowel diseases [BDs].</p><p><strong>Methods: </strong>Statements were issued by a panel of 11 European experts in IBD management and trial methodology, on four main topics: [I] study design; [II] eligibility, recruitment and organisation, flexibility; [III] outcomes; [IV] analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement [1 to 9; cut-off ≥7 for approval] with the statements by 18 additional European experts in IBD.</p><p><strong>Results: </strong>At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: seven for study design; six for eligibility, recruitment and organisation, flexibility; eight for outcomes; and four for analysis.</p><p><strong>Conclusions: </strong>Pragmatic, randomised, clinical trials can address important questions in IBD clinical practice, and may provide complementary, high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality, pragmatic, clinical trials that can aid decision making in choosing a management strategy for IBDs.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898405","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}
Martina Sciberras, Yvette Farrugia, Hannah Gordon, Federica Furfaro, Mariangela Allocca, Joana Torres, Naila Arebi, Gionata Fiorino, Marietta Iacucci, Bram Verstockt, Fernando Magro, Kostas Katsanos, Josef Busuttil, Katya De Giovanni, Valerie Anne Fenech, Stefania Chetcuti Zammit, Pierre Ellul
{"title":"Accuracy of Information given by ChatGPT for Patients with Inflammatory Bowel Disease in Relation to ECCO Guidelines.","authors":"Martina Sciberras, Yvette Farrugia, Hannah Gordon, Federica Furfaro, Mariangela Allocca, Joana Torres, Naila Arebi, Gionata Fiorino, Marietta Iacucci, Bram Verstockt, Fernando Magro, Kostas Katsanos, Josef Busuttil, Katya De Giovanni, Valerie Anne Fenech, Stefania Chetcuti Zammit, Pierre Ellul","doi":"10.1093/ecco-jcc/jjae040","DOIUrl":"10.1093/ecco-jcc/jjae040","url":null,"abstract":"<p><strong>Background: </strong>As acceptance of artificial intelligence [AI] platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of inflammatory bowel disease [IBD] remains unclear.</p><p><strong>Methods: </strong>In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: [1] Crohn's disease [CD], ulcerative colitis [UC], and malignancy; [2] maternal medicine; [3] infection and vaccination; and [4] complementary medicine. Responses given by ChatGPT were assessed for accuracy [1-completely incorrect to 5-completely correct] and completeness [3-point Likert scale; range 1-incomplete to 3-complete] by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines.</p><p><strong>Results: </strong>In terms of accuracy, most replies [84.2%] had a median score of ≥4 (interquartile range [IQR]: 2) and a mean score of 3.87 [SD: ±0.6]. For completeness, 34.2% of the replies had a median score of 3 and 55.3% had a median score of between 2 and <3. Overall, the mean rating was 2.24 [SD: ±0.4, median: 2, IQR: 1]. Though groups 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the four question groups [Kruskal-Wallis test p > 0.05]. However, statistical analysis for the different individual questions revealed a significant difference for both accuracy [p < 0.001] and completeness [p < 0.001]. The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning.</p><p><strong>Conclusion: </strong>This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinics and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195372","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":"Epigenetic Fingerprints in IBD: From Methylation Patterns to Clinical Implications.","authors":"Bram Verstockt","doi":"10.1093/ecco-jcc/jjae086","DOIUrl":"10.1093/ecco-jcc/jjae086","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422210","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":"Unravelling the Oral-Gut Axis: Interconnection Between Periodontitis and Inflammatory Bowel Disease, Current Challenges, and Future Perspective.","authors":"Himanshi Tanwar, Jeba Mercy Gnanasekaran, Devon Allison, Ling-Shiang Chuang, Xuesong He, Mario Aimetti, Giacomo Baima, Massimo Costalonga, Raymond K Cross, Cynthia Sears, Saurabh Mehandru, Judy Cho, Jean-Frederic Colombel, Jean-Pierre Raufman, Vivek Thumbigere-Math","doi":"10.1093/ecco-jcc/jjae028","DOIUrl":"10.1093/ecco-jcc/jjae028","url":null,"abstract":"<p><p>As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and inflammatory bowel disease [IBD], implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an 'oral-gut' axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a 'multi-hit' hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992207","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}
Joel R Rosh, Dan Turner, Jeffrey S Hyams, Marla Dubinsky, Anne M Griffiths, Stanley A Cohen, Kim Hung Lo, Lilianne Kim, Sheri Volger, Renping Zhang, Richard Strauss, Laurie S Conklin
{"title":"Outcomes in Adult Inflammatory Bowel Disease Clinical Trials: Assessment of Similarity Among Participants with Adolescent-onset and Adult-onset Disease.","authors":"Joel R Rosh, Dan Turner, Jeffrey S Hyams, Marla Dubinsky, Anne M Griffiths, Stanley A Cohen, Kim Hung Lo, Lilianne Kim, Sheri Volger, Renping Zhang, Richard Strauss, Laurie S Conklin","doi":"10.1093/ecco-jcc/jjae030","DOIUrl":"10.1093/ecco-jcc/jjae030","url":null,"abstract":"<p><strong>Background and aims: </strong>Most paediatric inflammatory bowel disease [IBD] studies are performed after medications are approved in adults, and the majority of participants in these studies are adolescents. We hypothesised that adolescent-onset IBD is not fundamentally different from adult-onset IBD. If this is correct, the value of delaying access to novel drugs in adolescents becomes questioned.</p><p><strong>Methods: </strong>Data from 11 randomised, double-blind, placebo-controlled, adult Phases 2 and 3 trials of four biologics were analysed. Participants were categorised as having adolescent- or adult-onset disease [diagnosed 12 to <18, or ≥18 years]. Multivariable modelling explored the association between age at diagnosis and response to treatment, after adjustment for disease duration, extent, and severity at baseline. Data from dose arms were pooled to evaluate similarity of therapeutic response between adolescent- and adult-onset IBD within the same trial [not between doses or across trials]. Ratios of odds ratios [ORs] between the two groups were evaluated.</p><p><strong>Results: </strong>Data from 6283 study participants (2575 with Crohn's disease [CD], 3708 with ulcerative colitis [UC]) were evaluated. Of 2575 study participants with CD, 325 were 12-<18 years old at diagnosis; 836 participants [32.4%] received placebo. Of 3708 participants with UC, 221 were 12-<18 years old at diagnosis; 1212 [33%] were receiving placebo. The majority of the ratios of ORs were within 2-fold, suggesting that responses in adolescent- and adult-onset participants are generally similar.</p><p><strong>Conclusion: </strong>Data presented lend support for extrapolating efficacy of biologics from adults to adolescents with IBD, which would facilitate earlier labelling and patient access.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975056","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}