Journal of Crohn's & colitis最新文献

{"title":"Safety and tolerability of anti-toll-like receptor 3, monoclonal antibody PRV-300 in patients with moderate-to-severe ulcerative colitis: a randomized phase 1B clinical trial (PULSE).","authors":"Jagoda Pokryszka, Gail M Comer, Camilla A Richmond, Francisco Leon, Walter Reinisch","doi":"10.1093/ecco-jcc/jjag154","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag154","url":null,"abstract":"<p><strong>Background & aims: </strong>PRV-300 is a fully human IgG4κ monoclonal antibody that binds the extracellular domain of human toll-like receptor 3, which is overexpressed in the inflamed colonic epithelium in patients with inflammatory bowel disease. This study aimed at proving its safety and efficacy in patients with ulcerative colitis (UC).</p><p><strong>Methods: </strong>Patients with moderate-to-severe UC (Mayo Clinical Score [MCS] 6-12) were randomized to receive 7 doses of PRV-300 intravenously or matched placebo (PBO). After a 12-week treatment period, participants underwent an 8-week follow-up. The primary endpoint was to assess the safety and tolerability of PRV-300. Secondary endpoints included assessment of pharmacodynamics, pharmacokinetics, immunogenicity, and endoscopic disease activity.</p><p><strong>Results: </strong>In total, 38 patients were randomized (28 in PRV-300 arm, 9 in placebo arm), of whom 32 completed the trial (24 and 8, respectively). Although TEAEs and TE-SAEs were numerically higher with PRV-300 than placebo (50.0% vs 11.1% and 39.3% vs 0.0%, respectively), the drug was well-tolerated, with only 7.1% (2/28) discontinuing therapy due to AEs and most events being mild, non-specific, or related to underlying disease. In colonic biopsies, PRV-300 had a greater, albeit not statistically significant, effect on the downregulation of TLR3 expression, but not on a UC gene expression signature. No differences in MCS and endoscopic severity were observed.</p><p><strong>Conclusions: </strong>While PRV-300 demonstrated an acceptable safety profile, TLR3 blockade did not translate into clinical benefit despite exploratory evidence of target engagement. Our results are challenging a pivotal role of the mode-of-action for the pathogenesis of UC (funded by Provention Bio).</p><p><strong>Clinical trial registration number: </strong>ClinicalTrials.gov (NCT03849599).</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225681","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":"Building sustainable IBD clinical research units: a practical toolbox emerging from a Belgian multi-stakeholder initiative.","authors":"Ingrid Arijs, Leonie Govaerts, Lynn Debrun, Liselotte Fierens, Katleen Franc, Hilde Kelchtermans, Charlotte Minsart, Catherine Reenaers, Louise Vandenbroucke, Laura Vansteenkiste, Jolien De Rechter, Bram Verstockt","doi":"10.1093/ecco-jcc/jjag144","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag144","url":null,"abstract":"<p><p>Clinical research is an essential pillar of modern inflammatory bowel disease (IBD) care, underpinning therapeutic innovation, biomarker discovery, precision medicine, and improvements in healthcare delivery. However, while international initiatives have successfully defined standards for clinical care, comparatively little attention has been devoted to the infrastructure required to conduct high-quality clinical research. Consequently, research capacity remains highly heterogeneous across centers, limiting patient access to clinical studies and reducing opportunities for collaborative research. To address this gap, a Belgian multi-stakeholder initiative involving patients, gastroenterologists, research nurses, study coordinators, and clinical researchers developed a practical toolbox for establishing and strengthening IBD clinical research units. Rather than defining rigid accreditation criteria, the toolbox distinguishes between essential components required for a functional research unit and important but non-essential elements that further improve quality, efficiency, and long-term sustainability. Structured across 3 complementary domains (administrative, operational, and collaborative) this framework provides a pragmatic roadmap that can support centers at different stages of research maturity. Beyond describing the toolbox, we discuss the concept of research readiness as a hallmark of excellence in modern IBD care and propose a roadmap for building sustainable research ecosystems. Although developed within the Belgian healthcare system, the principles presented are broadly applicable and may support the development of research capacity across healthcare systems and disease areas.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229713","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":"Challenges and opportunities facing inflammatory bowel disease in Sub-Saharan Africa: towards a contextually relevant research and practice agenda.","authors":"Sara Cooper, Gill Watermeyer, Dion Levin, Zozibini Mhlaba, Karin Davidson, Charles Bernstein, Dermot P B McGovern, David Epstein","doi":"10.1093/ecco-jcc/jjag135","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag135","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, has traditionally been considered a disease of Western, industrialized countries. Over the past few decades, however, many Sub-Saharan African (SSA) countries have experienced significant increases in cases. Yet, IBD remains highly neglected in SSA with most research conducted in high-income settings and treatment guidelines geared towards these settings. An emerging body of research on the sub-continent is highlighting several unique realities, dilemmas, and priorities facing IBD, and the need for evidence-based approaches that are more locally relevant and contextually tailored. In this viewpoint article we synthesize the challenges facing IBD in SSA and propose a research and practice agenda for addressing these, building on several promising initiatives already under way. Ultimately, we make a call to the international IBD community, researchers, funders, and policymakers to recognize the importance of IBD in SSA and join efforts to remedy global disparities in the quality, accessibility, and equity of IBD care.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168834","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":"Plasma lipopolysaccharide-binding protein (LBP), a proxy for intestinal permeability, relates to clinicopathological and immunological disease activity in inflammatory bowel disease patients at diagnosis and during disease course.","authors":"Daniëlle M H Barendregt, Bastiaan Tuk, Daniëlle H Hulleman-van Haaften, Anouk E Camman, Beatriz Calado, Meike H Grillmaier, Willem K Smits, Michail Doukas, Johanna C Escher, Lissy de Ridder, Janneke N Samsom","doi":"10.1093/ecco-jcc/jjag146","DOIUrl":"10.1093/ecco-jcc/jjag146","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal barrier healing is the treatment goal in ulcerative colitis (UC) and Crohn's disease (CD). Despite this, systematic analyses of the relationship between intestinal permeability and clinicopathological and immunological disease activity at diagnosis and during follow-up are lacking. Therefore, we assessed this relationship using plasma lipopolysaccharide-binding protein (LBP)-an indirect biomarker of systemic exposure to bacterial endotoxins-as a proxy for intestinal permeability, in a uniquely well-characterized pediatric inflammatory bowel disease (IBD) cohort.</p><p><strong>Methods: </strong>LBP was measured in 1083 longitudinal plasma samples of newly diagnosed pediatric UC (n = 61), CD (n = 115) (PIBD-SETQuality and TISKids prospective cohorts; median follow-up 628 days), and controls (IBD-negative, n = 33; healthy, n = 28). Its relationship with clinicopathological parameters and plasma immune proteomics was examined.</p><p><strong>Results: </strong>Plasma LBP was elevated and associated with clinicopathological disease activity in therapy-naive CD and UC. In UC, but not CD, LBP related to disease extent, and strongly and independently correlated to endoscopic and histological disease activity, providing additional explanatory value beyond routinely used blood-based biomarkers and inflammatory mediators (including CRP and IL-6). LBP correlated with disease-specific immune profiles linked to severe disease (IL-17/neutrophil/IFN-γ-related profile in UC; IFN-γ-related profile in CD). LBP decreased after induction therapy with corticosteroids in UC, and after exclusive enteral nutrition or anti-TNF (but not corticosteroids) in CD. LBP remained associated with clinicopathological disease activity during follow-up, particularly in UC.</p><p><strong>Conclusions: </strong>Plasma LBP relates to clinicopathological and immunological disease activity in IBD-especially UC-at diagnosis and during follow-up, and provides complementary information to routinely used blood-based biomarkers, arguing this simple, inexpensive parameter should be (re)considered for monitoring mucosal inflammation in UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149563","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":"Tofacitinib 20 vs 30 mg in acute severe ulcerative colitis: a double-blind randomized controlled trial.","authors":"Arshdeep Singh, Aakash Garg, Arshia Bhardwaj, Dharmatma Singh, Aman Thakur, Lagandeep Kaur, Ankuriti Singla, Lavanya Kapoor, Ramit Mahajan, Varun Mehta, Omesh Goyal, Yogesh K Gupta, Nishant Sharma, Vandana Midha, Ajit Sood","doi":"10.1093/ecco-jcc/jjag147","DOIUrl":"10.1093/ecco-jcc/jjag147","url":null,"abstract":"<p><strong>Background & aims: </strong>Tofacitinib has emerged as a promising therapy for acute severe ulcerative colitis (ASUC) due to its rapid onset of action. We compared the efficacy and safety of tofacitinib 20 mg/day vs 30 mg/day, both administered with intravenous corticosteroids (IVCS), in patients with ASUC.</p><p><strong>Methods: </strong>This was a double-blind, pilot, randomized controlled trial. Adult patients with ASUC were randomized to receive either tofacitinib 20 mg/day (Group 1) or 30 mg/day (Group 2) along with IVCS (hydrocortisone, 100 mg IV every 6 hours). The primary endpoint was clinical response by day 7. The secondary outcome was the cumulative probability of medical rescue therapy or post discharge escalation of therapy or colectomy within 90 days.</p><p><strong>Results: </strong>Seventy-two patients were randomized, with 36 allocated to each treatment group. At day 7, clinical response was achieved in 33/36 (91.7%) patients in Group 1 and 31/36 (86.1%) in Group 2(RR 1.06, 95% CI 0.90-1.25; P = .46). The absolute difference in response rates was 5.6% (95% CI -9.98% to 21.34%). Rescue therapy was required in 3 patients in Group 1 (all received infliximab) and 5 patients in Group 2 (2 underwent colectomy and 3 received infliximab). Event-free survival at 90 days, defined as the absence of rescue therapy, treatment escalation, or colectomy, was similar between groups (83.3% vs 80.2%; log-rank P = .74). Adverse events were predominantly mild, with no reported venous thromboembolism or major adverse cardiovascular events.</p><p><strong>Conclusions: </strong>In this exploratory pilot trial, no statistically significant differences were observed with tofacitinib 30 mg/day compared with 20 mg/day when administered with IVCS.</p><p><strong>Clinical trial registration number: </strong>Clinical Trials Registry-India: CTRI/2024/10/075098.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198154","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":"Contemporary multicentre validation and comparative performance of Day 1 prognostic scores in acute severe ulcerative colitis.","authors":"Deloshaan Subhaharan, Waled Mohsen, Asif Shahzad, Desmond Patrick, Lauren White, Pradeep Kakkadasam Ramaswamy","doi":"10.1093/ecco-jcc/jjag155","DOIUrl":"10.1093/ecco-jcc/jjag155","url":null,"abstract":"<p><strong>Background and aims: </strong>Early identification of steroid non-response in acute severe ulcerative colitis (ASUC) is critical to guide timely escalation of therapy. Several Day 1 prognostic scores have been proposed, but their comparative performance in contemporary cohorts remains uncertain, with limited direct head-to-head validation in real-world populations. We aimed to validate and directly compare the performance of previously proposed Day 1 prognostic scores, including the Admission Model for Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC), the Albumin-C reactive protein-Endoscopy (ACE) index, and the Risk of Rescue (ROR) score, in a contemporary multicenter ASUC cohort.</p><p><strong>Methods: </strong>We conducted a multicenter retrospective study of adults hospitalized with ASUC across three tertiary Australian centers between 2018 and 2023. The performance of ADMIT-ASC, ACE, and ROR scores for predicting steroid non-response, as defined by the Oxford criteria, was assessed using receiver operating characteristic analysis.</p><p><strong>Results: </strong>Among 238 patients, 134 (56.3%) met criteria for steroid non-response and required medical rescue therapy. All three scores demonstrated moderate discrimination, with AUROC highest for ROR (0.72), followed by ADMIT-ASC (0.68) and ACE (0.66) (P = .17). At published thresholds, ADMIT-ASC and ACE demonstrated high specificity but low sensitivity, whereas ROR provided greater sensitivity with lower specificity. In subgroup analyses, the discriminative performance of the Day 1 scores was broadly similar in biologic-naive and biologic-exposed patients.</p><p><strong>Conclusion: </strong>Day 1 prognostic scores demonstrate moderate performance in contemporary ASUC, with differing trade-offs between sensitivity and specificity. These findings support the use of Day 1 risk scores as adjuncts to early clinical decision-making in ASUC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148973","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":"Etrasimod reduces circulating and mucosal inflammatory lymphocyte populations and alters innate immune and non-immune cell signatures in intestinal mucosa: ELEVATE UC phase 3 clinical data.","authors":"Britta Siegmund, Catherine M Crosby, Rathi D Ryan, Justin Smith, Maria T Abreu, Séverine Vermeire, Iris Dotan, Keren M Rabinowitz, H Kiyomi Komori, Martina Goetsch, Karolina Wosik, John C Woolcott, Silvio Danese","doi":"10.1093/ecco-jcc/jjag159","DOIUrl":"10.1093/ecco-jcc/jjag159","url":null,"abstract":"<p><strong>Background and aims: </strong>Innate and adaptive immune cell dysregulation contributes to ulcerative colitis pathogenesis. The sphingosine 1-phosphate receptor modulator etrasimod showed efficacy in ulcerative colitis treatment in Phase 3 ELEVATE UC studies. Changes in circulating immune cells and mucosal cell types were characterized in etrasimod-treated patients with ulcerative colitis.</p><p><strong>Methods: </strong>Blood (etrasimod n = 525, placebo n = 257 patients) and mucosal biopsies (etrasimod n = 411, placebo n = 200 patients) from patients in the ELEVATE UC trials were used to assess cellular and molecular changes for etrasimod versus placebo in clinical remitters and non-remitters using immunophenotyping, transcriptomic and proteomic techniques.</p><p><strong>Results: </strong>Selective and partial reduction in circulating T- and B-cell subsets was observed for etrasimod versus placebo (Week 12), with greater effects on CD4+ T cells, including Treg and Th17 cells, than CD8+ T cells, and on naive T cells and T central memory cells than T effector memory cells, without difference between remitters and non-remitters. No significant effects on monocytes nor NK cell numbers were observed. Mucosal biopsies showed corresponding reductions in T- and B-cell subsets, myeloid cells and neutrophils accompanied by downregulation of interleukin-17 and interleukin-8 signaling in both tissue and blood, most prominently in remitters, where non-immune cell changes were consistent with tissue repair.</p><p><strong>Conclusions: </strong>Etrasimod treatment of patients with ulcerative colitis drives T- and B-lymphocyte subset reductions in blood and intestinal mucosa, neutrophil reductions in tissue and mucosal downregulation of inflammatory pathways associated with ulcerative colitis pathogenesis.</p><p><strong>Clinical trials registration number: </strong>ClinicalTrials.gov (NCT03945188; NCT03996369).</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170690","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":"Correction to: Third N-ECCO Consensus Statements on the Nursing Roles in Caring for Patients with Inflammatory Bowel Disease.","authors":"","doi":"10.1093/ecco-jcc/jjag138","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag138","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 10","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225644","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":"Declining rates of surgery in pediatric-onset inflammatory bowel disease: a Swedish nationwide register-based cohort study 2002-2022.","authors":"Helena Rolandsdotter, Kári Kristjánsson, Åsa H Everhov, Caroline Nordenvall, Petter Malmborg, Pär Myrelid, Matilda Bräutigam, Jonas F Ludvigsson, Ola Olén","doi":"10.1093/ecco-jcc/jjag127","DOIUrl":"10.1093/ecco-jcc/jjag127","url":null,"abstract":"<p><strong>Background and aims: </strong>The use of advanced therapies in pediatric-onset inflammatory bowel disease (PIBD) has increased substantially over the past two decades, while corresponding changes in surgical risk remain insufficiently studied. We aimed to compare the use of PIBD-related surgery across calendar periods.</p><p><strong>Methods: </strong>Using nationwide, population-based registers in Sweden, we identified all patients with PIBD, including Crohn's disease (CD) and ulcerative colitis (UC). We compared the cumulative incidence of IBD-related surgery by calendar period of first PIBD diagnosis (2002-2011 vs 2012-2022), with follow-up through adulthood. Trends in the use of advanced therapies were described for the same periods.</p><p><strong>Results: </strong>We identified 8200 patients with PIBD, with a median follow-up of 13.9 years for those diagnosed in 2002-2011 (n = 3751) and 4.3 years for 2012-2022 (n = 4449). The 5-year cumulative incidence of luminal surgical intervention decreased over time (9.6% vs 6.1%, P < .001). This reduction was observed for colectomy in UC (P = .044) but not in CD (P = .121). Patients with CD showed marked declines in small bowel surgery, including ileocecal resections, and in segmental colonic resections (P < .001 and P = .006). Between the first and second calendar period, the annual proportion of patients starting advanced therapies increased 2-fold for first-line use and 4-fold for second-line use, while third-line therapy was only observed in the later period.</p><p><strong>Conclusion: </strong>Over the past two decades, the cumulative incidence of several types of IBD-related surgery in PIBD has declined in parallel with a pronounced increase in the use of advanced therapies.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 9","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972750","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":"A therapeutic atlas of monogenic inflammatory bowel disease.","authors":"Pai-Jui Yeh, James E G Charlesworth, Henry Taylor, James J Ashton, Katrina Nash, Kin Hang Lam, Lissy de Ridder, Stephanie A Vuijk, Ziqing Ye, Ying Huang, Tania Bildstein, Wolfram Haller, Kelsey D J Jones, Dror S Shouval, Batia Weiss, Yu Lung Lau, Quynh Bui-Thi-Thuy, Aleixo M Muise, Duncan Richards, Simon Travis, Dan Turner, Holm H Uhlig","doi":"10.1093/ecco-jcc/jjag124","DOIUrl":"10.1093/ecco-jcc/jjag124","url":null,"abstract":"<p><strong>Background and aims: </strong>Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps.</p><p><strong>Methods: </strong>We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts.</p><p><strong>Results: </strong>Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n = 62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b.</p><p><strong>Conclusions: </strong>This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 9","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957670","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}