Sophie Vieujean, Bruce E Sands, Remo Panaccione, David T Rubin, Vipul Jairath, Silvio Danese, Laurent Peyrin-Biroulet, Stefan Schreiber, Séverine Vermeire, Geert D'Haens, Axel Dignass, Parambir S Dulai, Neeraj Narula, Walter Reinisch
{"title":"Comparison of the FDA and EMA guidance on drug development in ulcerative colitis: an expert panel review.","authors":"Sophie Vieujean, Bruce E Sands, Remo Panaccione, David T Rubin, Vipul Jairath, Silvio Danese, Laurent Peyrin-Biroulet, Stefan Schreiber, Séverine Vermeire, Geert D'Haens, Axel Dignass, Parambir S Dulai, Neeraj Narula, Walter Reinisch","doi":"10.1093/ecco-jcc/jjaf111","DOIUrl":"10.1093/ecco-jcc/jjaf111","url":null,"abstract":"<p><strong>Background and aims: </strong>The Food and Drug Administration (FDA) and European Medicines Agency (EMA) ensure the safety, efficacy, and security of treatments, including therapies for immune-mediated disorders such as inflammatory bowel disease (IBD). Their clinical trial guidelines aid sponsors in designing robust studies. While the EMA updated its guidelines for ulcerative colitis (UC) in 2018, the FDA issued new recommendations in April 2022. This paper compares these guidelines, assesses their implications for IBD clinical trials, and proposes strategies to improve alignment and trial efficiency.</p><p><strong>Methods: </strong>A comparative analysis of the FDA's 2022 guidelines and the EMA's 2018 guidelines for UC clinical trials was conducted. Key elements reviewed include trial population criteria, study design, assessment tools, endpoints, and safety considerations. Recommendations for optimization were developed in consultation with an expert panel.</p><p><strong>Results: </strong>The FDA's 2022 updates emphasize balanced participant representation, the use of full colonoscopy for endoscopic severity assessment, and introduce \"maintenance of remission\" as a new concept. Other novelties include updated statistical guidance and stricter safety requirements. While these updates enhance trial robustness, they also pose challenges for implementation.</p><p><strong>Conclusions: </strong>Harmonizing FDA and EMA guidelines is essential to streamline global IBD clinical trials, reduce redundancies, and improve patient outcomes. Recommendations include adopting less invasive assessments, standardizing remission definitions, and prioritizing patient-centered endpoints. These measures could reduce trial complexity, increase inclusivity, and accelerate the development of effective therapies for UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"19 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683901","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}
Lena Erkert, Melanie Kabisch, Reyes Gamez-Belmonte, Miguel Gonzalez-Acera, Jay V Patankar, Lena Schödel, Katharina Hofmann, Yara Wagner, Christina Plattner, Eva-Maria Spath, Ute Distler, Stefan Tenzer, Clemens Neufert, Markus F Neurath, Christoph Becker
{"title":"Pharmacological inhibitors of the gamma-secretase enzyme complex disrupt epithelial cell function triggering colitis in mice.","authors":"Lena Erkert, Melanie Kabisch, Reyes Gamez-Belmonte, Miguel Gonzalez-Acera, Jay V Patankar, Lena Schödel, Katharina Hofmann, Yara Wagner, Christina Plattner, Eva-Maria Spath, Ute Distler, Stefan Tenzer, Clemens Neufert, Markus F Neurath, Christoph Becker","doi":"10.1093/ecco-jcc/jjaf096","DOIUrl":"10.1093/ecco-jcc/jjaf096","url":null,"abstract":"<p><strong>Background and aims: </strong>Inhibiting γ-secretase-mediated Notch signaling has been explored as a potential treatment for Alzheimer's disease and cancer. However, clinical trials have revealed that this approach can lead to side effects, such as gut inflammation. Notch signaling has been shown to be a key mediator of intestinal epithelial homeostasis. We aimed to investigate the molecular mechanisms of γ-secretase inhibition-associated colitis.</p><p><strong>Methods: </strong>Mice and small intestinal organoids were treated with γ-secretase inhibitors and analyzed for intestinal epithelial cell (IEC) differentiation and inflammation-associated markers using different molecular and histological approaches, along with transcriptomic and proteomic analyses. To evaluate the role of the microbiome in colitis development, mice undergoing pharmacological γ-secretase inhibition were treated with antibiotics. Additionally, inflammatory bowel disease (IBD) patient samples and control samples were analyzed to assess the expression of Notch signaling pathway components in IECs.</p><p><strong>Results: </strong>This study shows that pharmacological γ-secretase inhibition induces inflammation in both the small and large intestine of mice, a phenotype that could be rescued upon microbiota depletion. Inhibiting the γ-secretase induced structural disruption of the epithelium and inflammatory cytokine release. On a molecular level, epithelial organoids exhibited disrupted IEC differentiation and impaired proliferation, associated with defective Notch signaling. Finally, analysis of IBD patients revealed deregulation of Notch pathway components within IECs.</p><p><strong>Conclusions: </strong>In conclusion, systemic use of γ-secretase inhibitors disrupts epithelial cell function by impairing IEC differentiation and triggering gut inflammation in mice. These findings should be considered when designing future therapeutic interventions involving γ-secretase inhibitors.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277070","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}
Julian Panés, Marla C Dubinsky, Yoh Ishiguro, Nidhi Shukla, Elena Dubcenco, Valencia Remple, Dolly Sharma, Remo Panaccione
{"title":"Achievement of long-term treatment goals in upadacitinib-treated patients with moderately to severely active ulcerative colitis: a post hoc analysis of phase 3 trial data.","authors":"Julian Panés, Marla C Dubinsky, Yoh Ishiguro, Nidhi Shukla, Elena Dubcenco, Valencia Remple, Dolly Sharma, Remo Panaccione","doi":"10.1093/ecco-jcc/jjaf095","DOIUrl":"10.1093/ecco-jcc/jjaf095","url":null,"abstract":"<p><strong>Background and aims: </strong>Comprehensive disease control is an important yet elusive treatment goal in ulcerative colitis (UC). We evaluated the effect of upadacitinib induction and maintenance treatment on composite clinical endpoints and normalization of important health-related quality of life (HRQoL) outcomes.</p><p><strong>Methods: </strong>Data from the U-ACHIEVE and U-ACCOMPLISH trials were analyzed. Clinical responders to upadacitinib 45 mg 8-week induction were re-randomized 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance. The percentage of patients achieving a composite clinical endpoint (clinical remission, complete symptom resolution, and Inflammatory Bowel Disease Questionnaire [IBDQ] remission) and a composite endpoint for normalization of HRQoL outcomes (Functional Assessment of Chronic Illness Therapy-Fatigue, IBDQ remission, Work Productivity and Activity Impairment Questionnaire-Ulcerative Colitis, 36-item Short Form Survey Physical Component Summary and Mental Component Survey, and EuroQol 5-Dimension 5-Level scores) was evaluated.</p><p><strong>Results: </strong>At induction week 8, more patients treated with upadacitinib 45 mg achieved the composite clinical endpoint vs placebo (6.4% vs 0.9%, P ≤ .001) and normalization of the composite HRQoL endpoint (18.9% vs 5.5%, P ≤ .001). At maintenance week 52, the composite clinical endpoint was achieved by 18.3% and 13.1% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 4.5% with placebo (P ≤ .001). Normalization of the composite HRQoL endpoint was achieved by 24.0% and 22.3% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 8.7% for placebo (P ≤ .001).</p><p><strong>Conclusions: </strong>Upadacitinib may help patients with moderately to severely active UC achieve complete symptom resolution, endoscopic remission, and normalization of HRQoL.</p><p><strong>Clinical registration numbers: </strong>U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026).</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251608","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}
Mohmmed Tauseef Sharip, Tim Raine, Nurulamin M Noor
{"title":"Hit the road JAK: is there still hope left for TYK2 inhibition in IBD?","authors":"Mohmmed Tauseef Sharip, Tim Raine, Nurulamin M Noor","doi":"10.1093/ecco-jcc/jjaf088","DOIUrl":"10.1093/ecco-jcc/jjaf088","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"19 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228072","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":"Restoring Prostacyclin/PGI2-PTGIR signaling alleviates intestinal fibrosis in Crohn's disease via fibroblast-specific YAP/TAZ inhibition.","authors":"Weijun Ou, Yaosheng Wang, Weimin Xu, Zhebin Hua, Xiaolei Wang, Wensong Ge, Wenjun Ding, Yingwei Chen, Chen-Ying Liu, Peng Du","doi":"10.1093/ecco-jcc/jjaf084","DOIUrl":"10.1093/ecco-jcc/jjaf084","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal obstruction caused by fibrosis is a common and serious complication of Crohn's disease (CD). Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motifs (TAZ), the transcriptional effectors of the Hippo signaling pathway, have emerged as key drivers of intestinal fibrosis. Systematic inhibition of YAP/TAZ failed to combat fibrotic progression, probably due to the vital role of epithelial YAP/TAZ in intestinal homeostasis.</p><p><strong>Methods: </strong>Enzyme-Linked Immunosorbent Assay (ELISA) and immunohistochemical staining were used to detect serum Prostaglandin I2 (PGI2) levels and PGI2 Receptor (PTGIR) in clinical samples derived from CD patients. Dual luciferase reporter and Cut & Run assays were performed to explore the transcriptional regulatory mechanisms of PTGIR and PGI2 synthase (PTGIS) by tumor necrosis factor α (TNF-α) and transforming growth factor-beta (TGF-β), respectively. Primary intestinal fibroblasts and a chronic colitis model were used for assessing the efficacy of a PTGIR agonist in combating fibrosis.</p><p><strong>Results: </strong>The Gαs-coupled PTGIR is expressed in intestinal fibroblasts but is barely expressed in intestinal epithelial cells. PTGIR transcription is directly activated by p65 in fibroblasts upon TNF-α stimulation. Importantly, PTGIS is transcriptionally suppressed by TGF-β, leading to the loss of endogenous antifibrotic PGI2-PTGIR signaling. Serum PGI2 levels are decreased in CD patients with stenosis and are negatively correlated with disease duration. The PTGIR agonist inhibited the profibrotic function of YAP/TAZ in intestinal fibroblasts in vitro and reversed intestinal fibrosis in vivo.</p><p><strong>Conclusions: </strong>The antifibrotic effects of PGI2-PTGIR signaling are impaired in CD. Restoring PGI2-PTGIR signaling is a pharmacologically tractable and cell-selective approach to targeting YAP/TAZ via PTGIR, which reverses intestinal fibrosis.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103439","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}
Kristi Kontola, Tuire Ilus, Heini Huhtala, Llona Helavirta, Pia Oksanen
{"title":"Risk of colectomy is decreasing among newly diagnosed Finnish ulcerative colitis patients.","authors":"Kristi Kontola, Tuire Ilus, Heini Huhtala, Llona Helavirta, Pia Oksanen","doi":"10.1093/ecco-jcc/jjaf081","DOIUrl":"10.1093/ecco-jcc/jjaf081","url":null,"abstract":"<p><strong>Background and aims: </strong>The risk of colectomy in patients with ulcerative colitis (UC) has decreased since the 20th century. Our aim was to determine the colectomy risk of newly diagnosed Finnish UC patients and compare the risk of the prebiological and biological era.</p><p><strong>Methods: </strong>We used the registry of the Social Insurance Institution of Finland to find newly diagnosed UC patients, and colectomies were collected from the Finnish Institute for Health and Welfare. The patients were stratified according to the year of UC diagnosis into 3 groups: 2000-2005 (prebiological), 2006-2012, and 2013-2020.</p><p><strong>Results: </strong>We identified 32 108 UC patients and 2195 colectomies performed on them. The 1-, 5-, and 10-year cumulative colectomy risk was 1.0%, 4.7%, and 7.3%, respectively. The risks declined with the incidence rate ratio (IRR) 0.98 (95% CI, 0.96-0.99), IRR 0.97 (CI, 0.96-0.98), and IRR 0.97 (CI, 0.96-0.99), respectively. Men and the pediatric group had higher risk of surgery (IRR 1.25, CI, 1.15-1.37 and IRR 1.69, CI, 1.51-1.89). Colectomy risks were lower in the last study era (IRR 0.757, CI, 0.574-0.997 in 1-year and IRR 0.70, CI, 0.61-0.82 in 5-year risk), and the 10-year risk was also decreased in the second era (IRR 0.87, CI, 0.78-0.97) compared to the prebiological era. The pediatric population had lower risk of surgery only in the last era, whereas the risk among the elderly remained constant.</p><p><strong>Conclusions: </strong>The risk of colectomy in UC patients has decreased in the 21st century.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012190","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}
Arno R Bourgonje, Susanne Ibing, Alexandra E Livanos, Danielle Y Ganjian, Carmen Argmann, Bruce E Sands, Marla C Dubinsky, Drew S Helmus, Henrik A Jacobsen, Lone Larsen, Tine Jess, Mayte Suarez-Fariñas, Bernhard Y Renard, Jean-Frédéric Colombel, Ryan C Ungaro
{"title":"Distinct perturbances in metabolic pathways associate with disease progression in inflammatory bowel disease.","authors":"Arno R Bourgonje, Susanne Ibing, Alexandra E Livanos, Danielle Y Ganjian, Carmen Argmann, Bruce E Sands, Marla C Dubinsky, Drew S Helmus, Henrik A Jacobsen, Lone Larsen, Tine Jess, Mayte Suarez-Fariñas, Bernhard Y Renard, Jean-Frédéric Colombel, Ryan C Ungaro","doi":"10.1093/ecco-jcc/jjaf082","DOIUrl":"10.1093/ecco-jcc/jjaf082","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with inflammatory bowel disease (IBD) exhibit distinct shifts in circulating metabolite levels linked to disease activity and phenotype, but associations with disease progression remain unexplored. Our aim was to investigate relationships between circulating metabolites and metabolic pathways with disease progression risk in patients with IBD.</p><p><strong>Methods: </strong>We performed an observational cohort study using the Mount Sinai Crohn's and Colitis Registry. Follow-up data were retrieved from longitudinal electronic health records. Untargeted metabolomic analysis was performed on baseline serum. Disease progression was defined as new systemic steroid or biological prescriptions, IBD-related hospitalization, or surgery. We used multivariable Cox proportional hazards (CoxPH) regression, L1-regularized CoxPH, and Random Survival Forest models to analyze metabolite associations with disease progression risk.</p><p><strong>Results: </strong>We studied 1292 metabolites in 277 patients with ulcerative colitis (UC) and 375 patients with Crohn's disease (CD). Over a median follow-up of 2 years, 57.5% experienced disease progression. In CD, 151 metabolites correlated with disease progression (false discovery rate [FDR] < 0.1): 81 (53.6%) associated with higher risk (enriched in amino acids, purine/pyrimidine metabolism, and bile acids) and 70 (46.4%) with lower risk (enriched in fatty acid oxidation, steroid biosynthesis, tryptophan, and antioxidants). In UC, 84 metabolites associated with disease progression (FDR < 0.1): 29 (34.5%) with increased risk (enriched in sphingolipids, hydrogen sulfide, and tyrosine metabolism) and 55 (65.5%) with decreased risk (enriched in steroid biosynthesis, histidine, and phenylalanine metabolism). Survival models incorporating a combination of metabolomic data and clinical parameters outperformed those based solely on clinical variables, including age, sex, disease location, disease behavior, disease extent, current and prior use of biologics, endoscopic disease activity, surgical history, and perianal disease.</p><p><strong>Conclusions: </strong>Specific metabolites and pathways are associated with disease progression in IBD, highlighting potential prognostic biomarkers and relevant pathways.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096605","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":"Histology in Inflammatory Bowel Disease: A Redundant Tool or a Valuable Prognostic Marker?","authors":"Matthias Lenfant, Gert De Hertogh, João Sabino","doi":"10.1093/ecco-jcc/jjaf064","DOIUrl":"10.1093/ecco-jcc/jjaf064","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063683","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}
Julia López De-La-Cruz, Fernando Gomollón, Javier Louro, Juan López Pérez, María Mercedes Nocito Colon, Beatriz Gallego Llera, Sandra García-Mateo, Samuel J Martínez-Domínguez, María Concepción Aso Gonzalvo, Carla J Gargallo-Puyuelo
{"title":"Impact of HLADQA1*05 and HLADQA1*03 on Safety and Loss of Response to Anti-Tumor Necrosis Factor in Patients With Inflammatory Bowel Disease.","authors":"Julia López De-La-Cruz, Fernando Gomollón, Javier Louro, Juan López Pérez, María Mercedes Nocito Colon, Beatriz Gallego Llera, Sandra García-Mateo, Samuel J Martínez-Domínguez, María Concepción Aso Gonzalvo, Carla J Gargallo-Puyuelo","doi":"10.1093/ecco-jcc/jjae178","DOIUrl":"10.1093/ecco-jcc/jjae178","url":null,"abstract":"<p><strong>Background: </strong>HLADQA1*05 is recently associated with heightened immunogenicity to anti-tumor necrosis factor (TNFα). We aimed to determine whether HLADQ1*05 is a risk factor for primary non-response, loss of response (LOR), or adverse events (AE) to first-line anti-TNFα in patients with inflammatory bowel disease.</p><p><strong>Methods: </strong>We performed a retrospective observational study enrolling biologic naïve patients with Crohn's disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients.</p><p><strong>Results: </strong>We enrolled 408 patients who started first-line infliximab (n = 211) and adalimumab (n = 197), with a mean follow-up of 7.6 years. Primary response at Week 24 occurred in 347 (85.0%), LOR in 133 (38.3%), and AE in 93 (22.8%). The HLADQA1*05 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA1*05 was an independent risk factor for LOR (adjusted hazard ratio [aHR] = 1.80, 95% CI = 1.21-2.67) and immunogenicity (aOR = 3.44, 95% CI = 1.12-11.92). HLADQA1*03 was a protective factor against LOR (aHR = 0.42, 95% CI = 0.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA1*05 increased the risk of LOR to infliximab but not to adalimumab and HLADQA1*03 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab, and the co-presentation of at least one allele of the HLADQA1*03 and HLADQA1*05 were risk factors for AE.</p><p><strong>Conclusions: </strong>HLADQA1*05 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA1*03 seems to play a protective role against LOR, particularly adalimumab. Female sex and infliximab are risk factors for AE.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683998","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}
Mads Damsgaard Wewer, Søren Lophaven, Peter L Lakatos, Lorant Gonczi, Riina Salupere, Hendrika Adriana Linda Kievit, Kári Rubek Nielsen, Jóngerð Midjord, Viktor Domislovic, Željko Krznarić, Natalia Pedersen, Jens Kjeldsen, Jonas Halfvarson, Shaji Sebastian, Adrian Goldis, Naila Arebi, Pia Oksanen, Anders Neumann, Vibeke Andersen, Konstantinos H Katsanos, Anastasios Koukoudis, Svetlana Turcan, Pierre Ellul, Juozas Kupcinskas, Gediminas Kiudelis, Mathurin Fumery, Ioannis P Kaimakliotis, Renata D'Inca, Silvia Lombardini, Vicent Hernandez, Alberto Fernandez, Ebbe Langholz, Pia Munkholm, Johan Burisch
{"title":"Long-term disease course of ulcerative colitis in a prospective European population-based inception cohort-an Epi-IBD cohort study.","authors":"Mads Damsgaard Wewer, Søren Lophaven, Peter L Lakatos, Lorant Gonczi, Riina Salupere, Hendrika Adriana Linda Kievit, Kári Rubek Nielsen, Jóngerð Midjord, Viktor Domislovic, Željko Krznarić, Natalia Pedersen, Jens Kjeldsen, Jonas Halfvarson, Shaji Sebastian, Adrian Goldis, Naila Arebi, Pia Oksanen, Anders Neumann, Vibeke Andersen, Konstantinos H Katsanos, Anastasios Koukoudis, Svetlana Turcan, Pierre Ellul, Juozas Kupcinskas, Gediminas Kiudelis, Mathurin Fumery, Ioannis P Kaimakliotis, Renata D'Inca, Silvia Lombardini, Vicent Hernandez, Alberto Fernandez, Ebbe Langholz, Pia Munkholm, Johan Burisch","doi":"10.1093/ecco-jcc/jjaf089","DOIUrl":"10.1093/ecco-jcc/jjaf089","url":null,"abstract":"<p><strong>Background and aims: </strong>The Epi-IBD cohort is a population-based inception cohort of patients with inflammatory bowel disease from 22 European centers. The aim was to assess the 10-year disease course of patients with ulcerative colitis (UC) across Europe.</p><p><strong>Methods: </strong>Patients were followed prospectively from the time of diagnosis in 2010 and 2011, with a uniform collection of data to the end of 2020. Associations between covariates and colectomy, progression to extensive disease, and hospitalization were analyzed separately by multivariable Cox regression analyses in a propensity-score-matched subpopulation to address regional differences.</p><p><strong>Results: </strong>A total of 873 UC patients were recruited (Eastern Europe: 196 [22.4%], Western Europe: 677 [77.5%]). The 10-year crude rate for the use of advanced therapy was comparable in Eastern (13%) and Western Europe (16%) (P > 0.9), and the median time from diagnosis until initiation of advanced treatment was similar, at 3 years. The need for colectomy remained comparable in Eastern and Western Europe, with a 10-year crude rate of 4% and 6% (Cox: P = 0.6), respectively. Likewise, disease progression to extensive disease (10-year rate: 17%, Cox: P = 0.06) and hospitalization (10-year rate: 23%, Cox: P = 0.2) were comparable across Europe. The use of advanced therapy and the early use of corticosteroids were both associated with an increased risk of colectomy (Cox: both P < 0.05).</p><p><strong>Conclusions: </strong>While the introduction of advanced therapies for UC has transformed the therapeutic landscape, their impact on colectomy rates, disease progression, and hospitalizations remains modest. Our findings highlight the need for continued innovation in UC treatment and the importance of individualized and targeted care to achieve optimal long-term outcomes.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210518","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}