Journal of Crohns & Colitis最新文献

{"title":"Bacterial Oncotraits Rather than Spatial Organization Are Associated with Dysplasia in Ulcerative Colitis.","authors":"Carlijn E Bruggeling, Maarten Te Groen, Daniel R Garza, Famke van Heeckeren Tot Overlaer, Joyce P M Krekels, Basma-Chick Sulaiman, Davy Karel, Athreyu Rulof, Anne R Schaaphok, Daniel L A H Hornikx, Iris D Nagtegaal, Bas E Dutilh, Frank Hoentjen, Annemarie Boleij","doi":"10.1093/ecco-jcc/jjad092","DOIUrl":"10.1093/ecco-jcc/jjad092","url":null,"abstract":"<p><strong>Background and aims: </strong>Colonic bacterial biofilms are frequently present in ulcerative colitis [UC] and may increase dysplasia risk through pathogens expressing oncotraits. This prospective cohort study aimed to determine [1] the association of oncotraits and longitudinal biofilm presence with dysplasia risk in UC, and [2] the relation of bacterial composition with biofilms and dysplasia risk.</p><p><strong>Methods: </strong>Faeces and left- and right-sided colonic biopsies were collected from 80 UC patients and 35 controls. Oncotraits [FadA of Fusobacterium, BFT of Bacteroides fragilis, colibactin [ClbB] and Intimin [Eae] of Escherichia coli] were assessed in faecal DNA with multiplex quantitative polymerase chain reaction [qPCR]. Biopsies were screened for biofilms [n = 873] with 16S rRNA fluorescent in situ hybridiation. Shotgun metagenomic sequencing [n = 265], and ki67-immunohistochemistry were performed. Associations were determined with a mixed-effects regression model.</p><p><strong>Results: </strong>Biofilms were highly prevalent in UC patients [90.8%] with a median persistence of 3 years (interquartile range [IQR] 2-5 years). Biofilm-positive biopsies showed increased epithelial hypertrophy [p = 0.025] and a reduced Shannon diversity independent of disease status [p = 0.015], but were not significantly associated with dysplasia in UC: adjusted odds ratio [aOR] 1.45, 95% confidence interval [CI] 0.63-3.40. In contrast, ClbB independently associated with dysplasia [aOR 7.16, 95% CI 1.75-29.28], and FadA and Fusobacteriales were associated with a decreased dysplasia risk in UC [aOR 0.23, 95% CI 0.06-0.83, p <0.01].</p><p><strong>Conclusions: </strong>Biofilms are a hallmark of UC; however, because of their high prevalence are a poor biomarker for dysplasia. In contrast, colibactin presence and FadA absence independently associate with dysplasia in UC and might therefore be valuable biomarkers for future risk stratification and intervention strategies.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1870-1881"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.","authors":"Piotr Eder, Bram Verstock, Emma Culver, Gabriele Dragoni, Lea Isabell Kredel, Joanna Wypych, Ana Garcia Garcia de Paredes, Magdalena Kaniewska, Haim Leibovitzh, Triana Lobaton, Marie Truyens, Grzegorz Oracz, Davide Giuseppe Ribaldone, Teresa Starzyńska, Abdenor Badaoui, Jean-Francois Rahier, Cristina Bezzio, Peter Bossuyt, Katherine Falloon, Daniela Pugliese, Catherine Frakes Vozzo, Tine Jess, Lone Larsen, Søren Schou Olesen, Partha Pal, María Chaparro, Dikla Dror, Pierre Ellul, Iga Gromny, Maria Janiak, Katarzyna Maciejewska, Noam Peleg, Ariella Bar-Gil Shitrit, Łukasz Szwed, Renata Talar-Wojnarowska, Yifat Snir, Roni Weisshof, Eran Zittan, Izabela Miechowicz, Idan Goren","doi":"10.1093/ecco-jcc/jjad097","DOIUrl":"10.1093/ecco-jcc/jjad097","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.</p><p><strong>Methods: </strong>An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD.</p><p><strong>Results: </strong>We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred.</p><p><strong>Conclusions: </strong>In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1791-1799"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.","authors":"João Sabino, Leonid Tarassishin, Caroline Eisele, Kelly Hawkins, Amelie Barré, Nile Nair, Alexa Rendon, Anketse Debebe, Mellissa Picker, Manasi Agrawal, Joanne Stone, James George, Peter Legnani, Elana Maser, Ching-Lynn Chen, Anne Thjømøe, Einar Mørk, Marla Dubinsky, Jianzhong Hu, Jean Frederic Colombel, Inga Peter, Joanna Torres","doi":"10.1093/ecco-jcc/jjad096","DOIUrl":"10.1093/ecco-jcc/jjad096","url":null,"abstract":"<p><strong>Background and aims: </strong>Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD.</p><p><strong>Methods: </strong>The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel.</p><p><strong>Results: </strong>We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points.</p><p><strong>Conclusion: </strong>Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1723-1732"},"PeriodicalIF":8.3,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9638347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major Adverse Cardiovascular Events by Baseline Cardiovascular Risk in Patients with Ulcerative Colitis Treated with Tofacitinib: Data from the OCTAVE Clinical Programme.","authors":"Stefan Schreiber, David T Rubin, Siew C Ng, Laurent Peyrin-Biroulet, Silvio Danese, Irene Modesto, Xiang Guo, Chinyu Su, Kenneth K Kwok, Hyejin Jo, Yan Chen, Arne Yndestad, Walter Reinisch, Marla C Dubinsky","doi":"10.1093/ecco-jcc/jjad104","DOIUrl":"10.1093/ecco-jcc/jjad104","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with inflammatory bowel disease have increased risk of atherosclerotic cardiovascular [CV] disease [ASCVD]. Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We report major adverse CV events [MACE] in the UC OCTAVE programme, stratified by baseline CV risk.</p><p><strong>Methods: </strong>Rates of MACE were analysed by baseline [first tofacitinib exposure] CV risk profile: prior ASCVD, or 10-year ASCVD risk categories [low, borderline, intermediate, high].</p><p><strong>Results: </strong>Of 1157 patients [2814.4 patient-years of exposure; ≤7.8 years' tofacitinib treatment], 4% had prior ASCVD and 83% had no prior ASCVD and low-borderline baseline 10-year ASCVD risk. Eight [0.7%] patients developed MACE; one had prior ASCVD. Incidence rates [unique patients with events/100 patient-years of exposure; 95% confidence intervals] for MACE were: 0.95 [0.02-5.27] in patients with prior ASCVD; and 1.81 [0.05-10.07], 1.54 [0.42-3.95], 0.00 [0.00-2.85], and 0.09 [0.01-0.32] in patients without prior ASCVD and with high, intermediate, -borderline, and low baseline 10-year ASCVD risk, respectively. For the 5/7 patients with MACE and without prior ASCVD, 10-year ASCVD risk scores were numerically higher [>1%] prior to MACE versus at baseline, primarily due to increasing age.</p><p><strong>Conclusions: </strong>Most patients receiving tofacitinib in the UC OCTAVE programme had low baseline 10-year ASCVD risk. MACE were more frequent in patients with prior ASCVD and higher baseline CV risk. This analysis demonstrates potential associations between baseline CV risk and MACE in patients with UC, suggesting CV risk should be assessed individually in clinical practice.</p><p><strong>Clinicaltrials.gov: </strong>NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1761-1770"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early intervention with biologic therapy in Crohn´s disease: how early is early?","authors":"Joana Revés, André Mascarenhas, Maria José Temido, Bárbara Morão, Catarina Neto Nascimento, Ana Rita Franco, Raquel R Mendes, Carolina Palmela, Cristina Chagas, Pedro Narra Figueiredo, Luísa Glória, Francisco Portela, Joana Torres","doi":"10.1093/ecco-jcc/jjad089","DOIUrl":"10.1093/ecco-jcc/jjad089","url":null,"abstract":"<p><strong>Background: </strong>Early biologic therapy within the first 18-24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation.</p><p><strong>Methods: </strong>This was a multicentre retrospective cohort study including newly diagnosed CD patients who started anti-tumour necrosis factor [TNF] therapy within 24 months from diagnosis. The timing of initiation of biologic therapy was categorised as ≤6, 7-12, 13-18, and 19-24 months. The primary outcome was CD-related complications defined as a composite of progression of Montreal disease behaviour, CD-related hospitalisations, or CD-related intestinal surgeries. Secondary outcomes included clinical, laboratory, endoscopic, and transmural remission.</p><p><strong>Results: </strong>We included 141 patients where 54%, 26%, 11%, and 9% started biologic therapy at ≤6, 7-12, 13-18, and 19-24 months after diagnosis, respectively. A total of 34 patients [24%] reached the primary outcome: 8% had progression of disease behaviour, 15% were hospitalised, and 9% required surgery. There was no difference in the time to a CD-related complication according to the time of initiation of biologic therapy within the first 24 months. Clinical, endoscopic, and transmural remission was achieved in 85%, 50%, and 29%, respectively, but no differences were found according to the time of initiation of biologic therapy.</p><p><strong>Conclusion: </strong>Starting anti-TNF therapy within the first 24 months after diagnosis was associated with a low rate of CD-related complications and high rates of clinical and endoscopic remission, although we found no differences with earlier initiation within this window of opportunity.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1752-1760"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9515262","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":"Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility.","authors":"Ronja Dörk, Penelope Pelczar, Ahmad M Shiri, Annika Volmari, Elisabeth Zierz, Anastasios Giannou, Marius Böttcher, Lidia Bosurgi, Samuel Huber, Carolin F Manthey","doi":"10.1093/ecco-jcc/jjad103","DOIUrl":"10.1093/ecco-jcc/jjad103","url":null,"abstract":"<p><strong>Background and aims: </strong>The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.</p><p><strong>Methods: </strong>We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.</p><p><strong>Results: </strong>Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.</p><p><strong>Conclusions: </strong>Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1858-1869"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696409","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":"Gut Microbiome-Generated Phenylacetylglutamine from Dietary Protein is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Model Possibly via Platelet Activation.","authors":"Rui Feng, Zhenyi Tian, Ren Mao, Ruiqi Ma, Wanrong Luo, Min Zhao, Xiaozhi Li, Yunchong Liu, Kan Huang, Liyuan Xiang, Xiaojun Zhuang, Bitao Huo, Tiantian Yu, Sifan Chen, Minhu Chen, Yijun Zhu","doi":"10.1093/ecco-jcc/jjad098","DOIUrl":"10.1093/ecco-jcc/jjad098","url":null,"abstract":"<p><strong>Objectives: </strong>Our aims were to better understand the interplay of diet and gut microbiota in Crohn's disease [CD], taking advantage of a new-onset treatment-naïve CD cohort. We focus on phenylacetylglutamine [PAGln], a diet-derived meta-organismal prothrombotic metabolite.</p><p><strong>Design: </strong>We collected faecal and serum samples from a CD cohort [n = 136] and healthy controls [n = 126] prior to treatment, and quantified serum PAGln using LC-MS/MS. Diet was assessed using food-frequency questionnaires. Mice [C57BL/6] were fed high/low-protein diets and administered dextran sodium sulphate [DSS] to examine plasma PAGly, thrombosis potential, and colitis severity. PAGly or saline was administered to DSS-induced colitis mice, and colitis severity and colonic tissue gene expression were examined. P-selectin and CD40L expression were determined in human platelet-rich plasma [n = 5-6] after exposure to platelet agonists following PAGln priming. Bioinformatic analysis and bacterial culturing identified the main contributor of PAGln in CD.</p><p><strong>Results: </strong>PAGln, a meta-organismal prothrombotic metabolite, is associated with CD. Administration of PAGly exacerbated colitis in a mouse model and upregulated coagulation-related biological processes. Antiplatelet medicine, dipyridamole, attenuated PAGly-enhanced colitis susceptibility. PAGln enhanced platelet activation and CD40L expression in platelet-rich plasma ex vivo. Further study revealed that high dietary protein intake and increased abundance of phenylacetic acid [PAA]-producing Proteobacteria mediated by phenylpyruvate decarboxylase act in concert to cause the elevated PAGln levels in CD patients.</p><p><strong>Conclusion: </strong>Taken together, ppdc-carrying Proteobacteria-generated PAGln from dietary protein is associated with CD and exacerbates colitis possibly via platelet-induced coagulation and inflammation These results suggest that PAGln is a potential early diagnostic marker and therapeutic target of CD.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1833-1846"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10033233","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":"Results of the Eighth Scientific Workshop of ECCO: Prevention and Treatment of Postoperative Recurrence in Patients With Crohn's Disease Undergoing an Ileocolonic Resection With Ileocolonic Anastomosis.","authors":"Marc Ferrante, Lieven Pouillon, Míriam Mañosa, Edoardo Savarino, Matthieu Allez, Christina Kapizioni, Naila Arebi, Michele Carvello, Pär Myrelid, Annemarie C De Vries, Pauline Rivière, Yves Panis, Eugeni Domènech","doi":"10.1093/ecco-jcc/jjad053","DOIUrl":"10.1093/ecco-jcc/jjad053","url":null,"abstract":"<p><p>Despite the introduction of biological therapies, an ileocolonic resection is often required in patients with Crohn's disease [CD]. Unfortunately, surgery is not curative, as many patients will develop postoperative recurrence [POR], eventually leading to further bowel damage and a decreased quality of life. The 8th Scientific Workshop of ECCO reviewed the available scientific data on both prevention and treatment of POR in patients with CD undergoing an ileocolonic resection, dealing with conventional and biological therapies, as well as non-medical interventions, including endoscopic and surgical approaches in case of POR. Based on the available data, an algorithm for the postoperative management in daily clinical practice was developed.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1707-1722"},"PeriodicalIF":8.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9311145","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":"Obefazimod: A First-in-class Drug for the Treatment of Ulcerative Colitis.","authors":"Séverine Vermeire, Virginia Solitano, Laurent Peyrin-Biroulet, Herbert Tilg, Silvio Danese, Hartmut Ehrlich, Didier Scherrer, Paul Gineste, Laurence d'Agay, Bruce E Sands","doi":"10.1093/ecco-jcc/jjad067","DOIUrl":"10.1093/ecco-jcc/jjad067","url":null,"abstract":"<p><p>Biologic agents and oral small molecules are the mainstays of inflammatory bowel disease [IBD] management. However, an unmet clinical need remains for additional agents with novel mechanism of action which are effective, safe, and disease-modifying; this is due to the substantial proportion of patients who do not respond, lose response, or develop intolerance to currently marketed products. microRNAs [miRNAs] that play a role in the modulation of signal transduction pathways implicated in the development of IBD hold the potential to be used as therapeutic targets. Recently, a novel first-in-class compound, obefazimod, originally conceived as a human immunodeficiency virus [HIV] infection drug, has shown great promise in phase II induction trials for ulcerative colitis [UC] patients. Findings from the maintenance phases of trials showed that long-term obefazimod treatment provides continued improvement in clinical symptoms of disease, with a substantial proportion of patients in clinical remission, and an overall good safety profile. With a novel mechanism of action, obefazimod is an orally available small molecule with anti-inflammatory properties through the specific and selective upregulation of miR-124 expression. The aim of this paper is to critically review the available evidence related to pharmacokinetics and pharmacodynamics, and to discuss the potential clinical implications of this first-in-class oral small molecule.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1689-1697"},"PeriodicalIF":8.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387679","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":"Shifting the Inflammatory Balance in Ulcerative Colitis Through Diet: A Mediterranean Diet Pattern is Associated with Improvements in Dysbiosis and Disease Activity.","authors":"Steven N Mathews, Dana J Lukin","doi":"10.1093/ecco-jcc/jjad095","DOIUrl":"10.1093/ecco-jcc/jjad095","url":null,"abstract":"","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":" ","pages":"1555-1556"},"PeriodicalIF":8.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675089","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}