Journal of Crohn's & colitis最新文献

{"title":"Medical and surgical therapies for patients with inflammatory bowel diseases and prior or coexisting cancer: a Danish nationwide cohort study.","authors":"Jonathan Plovgaard, Mads Damsgaard Wewer, Flemming Bendtsen, Johan Burisch","doi":"10.1093/ecco-jcc/jjag073","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag073","url":null,"abstract":"<p><strong>Background and aims: </strong>As a result of an aging population and the rising incidence of inflammatory bowel diseases (IBD) across all age groups, more patients with IBD are being diagnosed with cancer both before and after their IBD diagnosis. We describe the treatment of patients with IBD with prior or coexisting cancer relative to patients with IBD and no cancer.</p><p><strong>Methods: </strong>Danish national registers were used to identify incident and prevalent patients with IBD, drug exposure, and cancer status, from 1996 to 2022. Cox regressions were used to compare medications and the risk of surgery among patients with and without cancer.</p><p><strong>Results: </strong>In total 59 494 patients with IBD (20 551 Crohn's disease [CD; 34.5%], 38 943 ulcerative colitis [UC; 65.5%]) were included. Of those, 2675 (4.5%) had been diagnosed with cancer prior to IBD. Of the remaining 56 819 patients with IBD, 6636 (11.7%) had their first cancer develop after their IBD diagnosis. Prior cancer was associated with reduced immunomodulator use for CD and UC, and increased anti-tumor necrosis factor (anti-TNF) use in UC. Furthermore, patients with CD and UC and a history of cancer had an increased risk of undergoing IBD-related surgery during follow-up. Patients who developed cancer during the course of their IBD largely had their anti-TNF and immunomodulator therapy discontinued following a cancer diagnosis.</p><p><strong>Conclusions: </strong>Patients with IBD and prior or coexisting cancer were treated differently from patients with no history of cancer. We observed greater caution around initiating immunosuppressants for patients with prior cancer, while more patients required IBD-related surgery. Greater caution was observed around reinitiating immunosuppressants for patients diagnosed with cancer.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267685","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":"Effectiveness and safety of mirikizumab in patients with moderate-to-severe ulcerative colitis: the miri real multicenter study.","authors":"Ferdinando D'Amico, Fabrizio Fanizzi, Arianna Dal Buono, Roberto Gabbiadini, Olga M Nardone, Alessandra Zilli, Mariangela Allocca, Giorgia M Lauriola, Vipul Jairath, Laurent Peyrin-Biroulet, Gionata Fiorino, Fabiana Castiglione, Luca Massimino, Mauro Mastronardi, Alessandro Armuzzi, Silvio Danese","doi":"10.1093/ecco-jcc/jjag062","DOIUrl":"10.1093/ecco-jcc/jjag062","url":null,"abstract":"<p><strong>Background & aims: </strong>Mirikizumab, an IL-23 p19-targeting monoclonal antibody, is approved for moderate-to-severe ulcerative colitis (UC). Real-world evidence on its effectiveness and safety remains limited. We evaluated its effectiveness and safety in a real-world setting.</p><p><strong>Methods: </strong>This retrospective multicenter study included adult UC patients treated with mirikizumab at 5 Italian centers (June 2024-October 2025), with ≥24 weeks of follow-up. The primary outcome was clinical remission (CR, pMS ≤ 2 with rectal bleeding 0) at week(w)12. Secondary outcomes included intestinal ultrasound (IUS) remission, endoscopic remission, bowel urgency (BU) remission, fecal calprotectin (FC) normalization, and safety profile.</p><p><strong>Results: </strong>A total of 236 patients (60.2% male; median age 47) were included. 77.5% had prior exposure to advanced therapy. Mirikizumab significantly reduced pMS at w12 and w24 (both P < .001), with clinical remission in 46.6% and 55.5%, respectively. Mayo endoscopic score improved at both timepoints (P < .01 and P < .001) with 38% achieving endoscopic remission at w24. IUS remission was nonsignificant at w12 but significant at w24 (P < .0001). BU and FC improved at both timepoints (P < .001). Remission rates were similar in biologic-naive and biologic-exposed patients. Discontinuations were uncommon, adverse events were infrequent and non-serious, and liver tests showed no clinically relevant changes.</p><p><strong>Conclusions: </strong>In this real-world multicenter cohort, mirikizumab was associated with meaningful improvements across clinical, endoscopic, biochemical, and ultrasound outcomes, with low discontinuation rates and a favorable safety profile through 24 weeks. These findings support the effectiveness of selective IL-23 inhibition in routine care, including in patients with prior exposure to advanced therapies.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201804","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":"Multiomics analysis dissects the molecular foundation of perianal fistulas associated with Crohn's disease and of cryptoglandular origin.","authors":"Céline Mamie, Daniela Cabalzar-Wondberg, Matthias Turina, Marcin Wawrzyniak, Benjamin Misselwitz, Nicola Zamboni, Claudia Gottier, Silvia Lang, Gerhard Rogler, Alvaro Avivar-Valderas, Olga de la Rosa, Ninfa Candela, Jay Tang, Yasser Morsy, Michael Scharl","doi":"10.1093/ecco-jcc/jjag080","DOIUrl":"10.1093/ecco-jcc/jjag080","url":null,"abstract":"<p><strong>Background and objective: </strong>Perianal fistulas, either of cryptoglandular origin (CgF) or associated with Crohn's disease (CDF), have limited treatment options and pose a tremendous burden for affected patients. We recently showed that the epithelial-mesenchymal transition (EMT) contributes to CDF pathogenesis, but detailed mechanisms need further evaluation. Here, we performed multiomics analysis to gain further molecular insights into fistula pathogenesis.</p><p><strong>Design: </strong>Rectal biopsies, swabs, fistula curettage, and serum samples were derived from patients with either CDF (n = 23) or CgF (n = 17) and analyzed by bulk RNA sequencing, metagenomics, untargeted metabolomics, or multiplex-ELISA, where appropriate.</p><p><strong>Results: </strong>Transcriptomics revealed striking differences in gene expression between rectal mucosa and fistula tract samples. However, the transcriptomes of CDF and CgF were comparable, and genes involved in EMT, inflammation and tumor necrosis factor signaling were prominent in both fistula types. A set of 18 genes was found to be differentially expressed in CDF and CgF and might allow discrimination. The overall microbiome composition within fistula tracts did not differ between CDF and CgF patients, but there was a significant difference in rectal microbiome compositions. On a species level, we detected an enrichment of disease-specific, pathogenic species in the fistula tracts. Of note, Bacteroides ssp., Fusobacterium animalis, and Staphylococcus aureus prevailed within CDF.</p><p><strong>Conclusion: </strong>Our data demonstrate only minor differences in the transcriptome and the microbiome between CDF and CgF, but clear differences when compared to rectal mucosa biopsies. Thus, our data suggest that the molecular makeup underlying the pathophysiology of fistulas might be comparable between CDF and CgF.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364436","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":"Impaired keratinization activity in perianal Crohn's fistulas is associated with poor prognosis.","authors":"Marte A J Becker, Pim J Koelink, Sarah Ouahoud, Sander M Meisner, Vanesa Muncan, Gerald Nabozny, Frank Li, Job Saris, Willem A Bemelman, Geert R D'Haens, Christianne J Buskens, Manon E Wildenberg","doi":"10.1093/ecco-jcc/jjag092","DOIUrl":"10.1093/ecco-jcc/jjag092","url":null,"abstract":"<p><strong>Background: </strong>Perianal fistulas remain a major complication in Crohn's disease, profoundly impacting quality of life. Although often therapy refractory, strong heterogeneity exists between patients, both in clinical behavior and therapy response. In this study, we aimed to identify biological factors involved in the clinical behavior of perianal fistulas, allowing better stratification.</p><p><strong>Methods: </strong>Forty-nine patients were included (Crohn's n = 36, cryptoglandular n = 13). Gene expression was analyzed in internal fistula openings and tracts by RNA sequencing. Data were verified using spatial transcriptomics and functionally in human adult organoid cultures. A gene-module score for keratinization activity was calculated and correlated to the Crohn's TOpClass classification as well as to long-term fistula outcomes.</p><p><strong>Results: </strong>Perianal fistulas were associated with the development of stratified squamous epithelium, expressing specific keratins (KRT5, KRT7, and KRT13). In human organoid models, exposing intestinal mucosa to a pro-inflammatory cytokine mixture partially induced similar changes, supporting rectal mucosal redifferentiation in response to perianal wounding. A gene-module score based on the keratinization-associated markers showed a decreasing gradient from cryptoglandular to mild Crohn-related to severe Crohn-related fistula (0.448 vs. -0.125 vs. -0.448, P = .018). Interestingly, the score was also predictive of long-term outcomes: Patients with low keratinization often showed progressive disease (14/20 patients), whereas this was not seen in the high keratinization group (0/16, P < .001).</p><p><strong>Conclusion: </strong>We identify an epithelial redifferentiation process characterized by a keratinization-associated gene module as part of the healing process in perianal fistula. The extent of the keratinization not only distinguished Crohn-related from cryptoglandular fistulas but also aligned with disease severity and healing potential.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364463","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":"Pro-inflammatory intestinal Th17-cells are tissue-resident, accumulate in the epithelia in Crohn's disease, and predict unresponsiveness to vedolizumab.","authors":"Moira Paroni, Carmen Faggiano, Camilla Righetti, Irene Dusetti, Valeria Ranzani, Giorgia Moschetti, Daniele Noviello, Chiara Vasco, Maurizio Vecchi, Paolo Landini, Federica Facciotti, Sergio Abrignani, Flavio Caprioli, Jens Geginat","doi":"10.1093/ecco-jcc/jjag055","DOIUrl":"10.1093/ecco-jcc/jjag055","url":null,"abstract":"<p><p>We recently identified a population of pro-inflammatory intestinal CCR5+Th17-cells (proinflammatory Th17, pTh17) associated with intestinal inflammation in Crohn's Disease (CD) and activated by CD-associated adherent-invasive Escherichia coli. Here, we report that intestinal pTh17-cells in CD expressed genes characteristic of tissue-resident memory T-cells (TRM). They expressed high levels of CD69 and CD103 on the cell surface and accumulated in the intraepithelial lymphocyte (IEL) compartment in CD. Consistently, single T-cell RNA sequencing in CD unveiled that intraepithelial Th17-cells displayed a gene signature of activated pTh17-cells.In peripheral blood, pTh17-cells with gut-homing potential were hardly detectable. Conversely, conventional CCR5-Th17-cells (\"cTh17\") were present and expressed increased levels of α4β7-integrin in the blood of IBD patients. Consistently, intestinal cTh17-cells were reduced after treatment with vedolizumab, which blocks α4β7-integrin-mediated gut-homing of lymphocytes. Importantly, unresponsiveness to vedolizumab in CD was associated with increased frequencies of preexisting intestinal pTh17-cells with high sensitivity and specificity. We conclude that intestinal pTh17-cells are tissue-resident cells, which could be generated from circulating cTh17 precursor cells in the gut. Moreover, our findings are consistent with a key pathogenic role of intraepithelial Th17-cells in CD and suggest that monitoring intestinal pTh17-cells may predict unresponsiveness to vedolizumab.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213784","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":"Micronutrients are associated with endoscopic postoperative recurrence in Crohn's disease: a multicenter prospective cohort study in North America.","authors":"Michiel T J Bak, Karen Boland, Shadi Nayeri, Krzysztof Borowksi, Pablo A Olivera, Cristian Hernandez-Rocha, Williams Turpin, Joanne M Stempak, Steven R Brant, Judy H Cho, Richard H Duerr, Talin Haritunians, Mark G Lazarev, Emebet Mengesha, Dermot P B McGovern, John D Rioux, L Philip Schumm, Sun-Ho Lee, Mark S Silverberg","doi":"10.1093/ecco-jcc/jjaf148","DOIUrl":"10.1093/ecco-jcc/jjaf148","url":null,"abstract":"<p><strong>Background and aims: </strong>Diet may influence the disease course in inflammatory bowel disease, but its role in postoperative outcomes for Crohn's disease (CD) remains unclear. This study aimed to assess the association of macro- and micronutrient intake with endoscopic postoperative recurrence (ePOR) in a prospective multicenter cohort.</p><p><strong>Methods: </strong>Patients with CD following ileocolic resection were prospectively recruited from six North American centers. Primary study outcome was ePOR (modified Rutgeerts' score ≥i2a) during follow-up. Nutritional intake was assessed through 2-day food diaries verified by dietitian-delivered interview. Associations between nutrient intake and ePOR were evaluated. Random forest models with 10-fold cross-validation assessed the predictive value of nutrients and clinical factors for ePOR.</p><p><strong>Results: </strong>A total of 520 food diaries from 103 patients were analyzed; 37 patients (36%) experienced ePOR. Univariate analysis identified 8 nutrients associated with ePOR including lower intake of isoflavones (genistein, daidzein, glycitein; P < .01), inositol (P < .01), pinitol (P = .02), provitamin-A carotenoid (P < .01), xylitol (P = .03) and parinaric Acid (P = .03). Sensitivity analysis confirmed the association of lower intake of all isoflavones (P < .01) and pinitol (P = .04) with ePOR at first postoperative colonoscopy. Random forest models showed poor discrimination for clinical factors alone (area under the curve [AUC] 0.59) but an acceptable discrimination for nutrients alone (AUC 0.67), which improved when combining nutrients and clinical factors (AUC 0.71).</p><p><strong>Conclusion: </strong>Lower intake of specific micronutrients is associated with ePOR in CD patients. A machine-learning model combining nutrient intake and clinical factors enhanced the prediction of ePOR. These findings highlight the importance of postoperative nutritional assessment and suggest dietary interventions may help prevent postoperative recurrence in CD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983594","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":"ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.","authors":"Michel Adamina, Peter Kienle, María Chaparro, Bram Verstockt, Silvia Minozzi, Mariangela Allocca, Raja Atreya, Nicolas Avellaneda, Manuel Barreiro-De Acosta, Robert Battat, Dominik Bettenworth, Irina Blumenstein, Steven R Brown, John P Burke, Flavio Caprioli, María José Casanova, Niki Christou, Anthony De Buck Van Overstraeten, Glen Doherty, Piotr Eder, Alaa El-Hussuna, Pierre Ellul, Massimo Claudio Fantini, Federica Furfaro, Thomas Greuter, Karl Hazel, Stefan Holubar, Christina Kapizioni, Uri Kopylov, Rupert W Leong, Sezai Leventoglu, Jimmy K Limdi, Nurulamin M Noor, Ioannis Papaconstantinou, Georgios Peros, Lieven Pouillon, Catherine Reenaers, Simone Saibeni, Carsten Schmidt, Paula Sousa, Laurents P S Stassen, Mathieu Uzzan, Sophie Vieujean, Eva Visser, Torsten Kucharzik, Javier P Gisbert, Pär Myrelid","doi":"10.1093/ecco-jcc/jjag072","DOIUrl":"10.1093/ecco-jcc/jjag072","url":null,"abstract":"<p><p>This is the second of two articles presenting the European Crohn's and Colitis Organisation [ECCO] evidence‑based consensus guidelines on the management of adult patients with ulcerative colitis [UC]. The first article covers the medical management of UC, including acute severe colitis. The present article addresses the surgical management of medically refractory UC, including the general surgical approach and perioperative optimisation, surgical strategies and techniques, and recommended levels of centre expertise and surgical specialisation. Together, these two articles aim to inform shared decision‑making and to guide clinicians and healthcare professionals involved in the care of patients with UC, drawing on the best available evidence.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364497","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":"The impact of global recruitment and country income on placebo rates in inflammatory bowel disease clinical trials.","authors":"Shane W Goodwin, Yuhong Yuan, Siddharth Singh, Virginia Solitano, Vineet Ahuja, Sudheer Kumar Vuyyuru, Mohammad Shehab, Neeraj Narula, Christopher Ma, Vipul Jairath","doi":"10.1093/ecco-jcc/jjag081","DOIUrl":"10.1093/ecco-jcc/jjag081","url":null,"abstract":"<p><strong>Introduction: </strong>Despite progress in understanding placebo effects in clinical trials of inflammatory bowel disease (IBD), there is a limited understanding of how socioeconomic factors of recruiting countries impact placebo rates. We investigated the association of socioeconomic factors across recruitment sites on placebo rates in IBD randomized controlled trials.</p><p><strong>Methods: </strong>We examined the association of clinical and endoscopic remission and response to the weighted Gross National Index (GNI) per capita, Human Development Index (HDI), and out-of-pocket health expenditures as a percentage of current health expenditures (OOP_CHE) of identified trials using mixed effects linear regression.</p><p><strong>Results: </strong>Across 76 trials (Crohn's disease [CD]: n = 32; ulcerative colitis [UC]: n = 44), placebo response rates over time were largely stable, with a small increase across time in clinical remission for CD trials (β = 0.4% per increase in study year, 95% CI: 0.3%-0.84%, P = .04) and a small decrease across time in endoscopic response for UC trials (β = -1.39% per increase in study year, 95% CI: -1.79, -0.99, P < .001). Clinical response was most susceptible to changes in socioeconomic factors in IBD trials (β = -2.96% per 10 000 USD increase in study GNI, 95% CI: -4.98, -0.95%, P = .004; P < .05 for HDI and OOP_CHE). Across both conditions, decreases in clinical response were associated with increases in HDI and OOP_CHE (CD HDI: β = -1.15% per 0.01 increase in study HDI, 95% CI: -2.24, -0.06%, P = .04; UC HDI: β = -0.66% per 0.01 increase in study HDI, 95% CI: -1.19, -0.12%, P = .02).</p><p><strong>Discussion: </strong>We found that placebo clinical response was most susceptible to influences of site-level socioeconomic wellbeing. These findings highlight that estimation of placebo rates in trial planning should account for geographic location of recruiting sites.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 6","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335178","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":"Comparative risk of serious infection in patients with ulcerative colitis treated with JAK inhibitors.","authors":"Antoine Meyer, Anaïs Bertrand, Antoine Martin, Franck Carbonnel, Aurélien Amiot","doi":"10.1093/ecco-jcc/jjag053","DOIUrl":"10.1093/ecco-jcc/jjag053","url":null,"abstract":"<p><strong>Introduction: </strong>While Janus kinase inhibitors (JAKi) have been associated with an increased risk of serious infections compared with biologics in patients with ulcerative colitis (UC), data comparing the risk of infection across individual JAKi remain limited. We aimed to compare the risk of serious infections among patients with UC treated with tofacitinib, upadacitinib, or filgotinib.</p><p><strong>Methods: </strong>We conducted a nationwide cohort study using the French National Health Data System, including UC patients aged >15 years who initiated tofacitinib, upadacitinib, or filgotinib between 2019 and 2025. We assessed the risk of serious infection (defined as requiring hospitalization) according to treatment exposure. Propensity score weighting accounted for indication bias.</p><p><strong>Results: </strong>Overall, 237 serious infections occurred among 6449 JAKi initiations: 2735 used upadacitinib, 2825 tofacitinib, and 889 filgotinib. Median age was 39 years, 49.5% were women, and median time since UC diagnosis was 7.1 years. Incidence rates per 1000 patient-years were 38.8 for upadacitinib, 30.6 for tofacitinib, and 28.4 for filgotinib. Compared with upadacitinib, adjusted hazard ratios for serious infection were 0.93 (95% CI: 0.70-1.24) for tofacitinib and 0.88 (95% CI: 0.56-1.39) for filgotinib. No differences were observed across infection sites or pathogen types. Higher doses of upadacitinib and tofacitinib were associated with increased infection risk. The risk of non-severe infections, particularly against herpes simplex virus and varicella zoster virus, was highest with upadacitinib and lowest with filgotinib.</p><p><strong>Conclusion: </strong>Tofacitinib, upadacitinib, and filgotinib were associated with similar risks of serious infection in patients with UC. Infection risk appeared to be driven primarily by dose rather than by type of JAKi.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 5","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876942","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 biomarkers in inflammatory bowel diseases-computational challenges and opportunities.","authors":"Seokjun Lee, Jaesub Park, Hyun Chang Lee, Xingze Xu, Ellie Slater, Marco Gasparetto, Namshik Han, Matthias Zilbauer","doi":"10.1093/ecco-jcc/jjag022","DOIUrl":"10.1093/ecco-jcc/jjag022","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD) remain a therapeutic challenge due to their heterogeneous nature and the absence of clinically actionable biomarkers to guide precision treatment. While multi-omics studies have advanced our understanding of the disease, meaningful translation into practice has been hindered by lack of validation and a need to move from association to a more generalizable signal. Epigenetics, particularly DNA methylation, offers a promising lens to capture disease-relevant regulatory states that reflect both genetic predisposition and environmental influences. However, the path to clinical adoption has been limited by persistent computational hurdles. Here we synthesize the current landscape of IBD biomarker discovery and highlight the conceptual advantages of epigenetic signatures. We outline the main obstacles that have limited clinical translation to date, including data heterogeneity, batch effects, and the challenge of distinguishing functional \"driver\" from non-functional \"passenger\" epigenetic changes. We then discuss how recent advances in computational methodology-spanning data harmonization, integrative modeling, and interpretable machine learning-can help bridge the gap between complex datasets and reliable, deployable biomarkers. Finally, we propose a forward-looking roadmap for study design and validation aimed at moving the field toward routine clinical implementation, thereby realizing the full potential of epigenetics in IBD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 5","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990560","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}