Inflammatory Bowel Diseases最新文献

{"title":"Target Trial Emulation: Improving the Quality of Observational Studies in Inflammatory Bowel Disease Using the Principles of Randomized Trials.","authors":"Sailish Honap, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1093/ibd/izae131","DOIUrl":"10.1093/ibd/izae131","url":null,"abstract":"<p><p>The past decade has seen a substantial increase in the number of randomized controlled trials (RCTs) conducted in inflammatory bowel disease (IBD). Randomized controlled trials are the gold standard method for generating robust evidence of drug safety and efficacy but are expensive, time-consuming, and may have ethical implications. Observational studies in IBD are often used to fill the gaps in evidence but are typically hindered by significant bias. There are several approaches for making statistical inferences from observational data with some that focus on study design and others on statistical techniques. Target trial emulation is an emerging methodological process that aims to bridge this gap and improve the quality of observational studies by applying the principles of an ideal, or \"target,\" randomized trial to routinely collected clinical data. There has been a rapid expansion of observational studies that have emulated trials over the past 5 years in other medical fields, but this has yet to be adopted in gastroenterology and IBD. The wealth of nonrandomized clinical data available through electronic health records, patient registries, and administrative health databases afford innumerable hypothesis-generating opportunities for IBD research. This review outlines the principles of target trial emulation, discusses the merits to IBD observational studies in reducing the most common biases and improving confidence in causality, and details the caveats of using this approach.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"843-849"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and Therapeutic Challenges in Severe Peristomal Pyoderma Gangrenosum.","authors":"Bernadett Farkas, Emese Ivány, Anita Bálint, Peter Bacsur, Tamás Molnár, Klaudia Farkas","doi":"10.1093/ibd/izae167","DOIUrl":"10.1093/ibd/izae167","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"885-886"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal and Transmural Healing and Long-term Outcomes in Crohn's Disease.","authors":"Bruce E Sands, Silvio Danese, J Casey Chapman, Khushboo Gurjar, Stacy Grieve, Deepika Thakur, Jenny Griffith, Namita Joshi, Kristina Kligys, Axel Dignass","doi":"10.1093/ibd/izae159","DOIUrl":"10.1093/ibd/izae159","url":null,"abstract":"<p><strong>Background: </strong>Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease.</p><p><strong>Methods: </strong>Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease.</p><p><strong>Results: </strong>A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH.</p><p><strong>Conclusions: </strong>Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"857-877"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn's Disease.","authors":"Teagan S Edwards, Shaun S C Ho, Stephanie C Brown, Laura Appleton, Briana R Smith, Grace M Borichevsky, Akhilesh Swaminathan, Christopher M A Frampton, Richard B Gearry, Anthony J Kettle, Andrew S Day","doi":"10.1093/ibd/izae262","DOIUrl":"10.1093/ibd/izae262","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived enzyme that produces hypochlorous acid, as a marker of disease activity in children with CD.</p><p><strong>Methods: </strong>This observational study assessed myeloperoxidase (MPO) levels in fecal samples from children aged <17 years with CD (51 with active or 42 inactive disease) measured by enzyme-linked immunosorbent assay (ELISA) and compared to controls (35 healthy siblings and 15 unrelated well children). Results were correlated with fecal calprotectin, serum C-reactive protein, urinary glutathione sulfonamide (a biomarker of hypochlorous acid), and disease activity scores. Differences between groups were assessed by analysis of variance. Receiver-operating-characteristic curves were used to assess how biomarkers predicted disease and disease activity.</p><p><strong>Results: </strong>Fecal myeloperoxidase activity and fMPO protein correlated with fecal calprotectin (r = 0.78, P < .0001, and r = 0.81, P < .0001, respectively). Fecal myeloperoxidase activity and protein levels were significantly higher (P ≤ .0001) in individuals with active disease compared to healthy sibling controls, unrelated well children, and those with inactive disease. A 9.7 µg/g fMPO protein cutoff distinguished inactive from active disease (sensitivity = 75%, specificity = 76%). Urinary GSA was elevated in children with active disease (P < .0001) and correlated with fMPO protein (r = 0.43, P = .0002) in a subset of 72 children with IBD and controls.</p><p><strong>Conclusions: </strong>Fecal myeloperoxidase may be superior to fCal at reflecting disease severity in children with CD and produces the damaging oxidant hypochlorous acid during active inflammation.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"800-811"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologic Anticoagulation Is Associated With a Lower Risk of Recurrent Venous Thromboembolic Events During Janus Kinase Inhibitor Use for Patients With a Prior Thrombosis.","authors":"Jeffrey A Lowell, Garvita Sharma, Arun Swaminath, Keith Sultan","doi":"10.1093/ibd/izae100","DOIUrl":"10.1093/ibd/izae100","url":null,"abstract":"<p><strong>Background: </strong>Janus kinase (JAK) inhibitors tofacitinib and upadacitinib are effective therapies for inflammatory bowel disease and rheumatologic disorders but currently possess a warning for increased venous thromboembolism (VTE) risk. Some patients with a history of VTE may benefit from a JAK inhibitor, but the risk of recurrent VTE with JAK inhibitor use is unclear. Our goal was to observe rates of new VTE events after starting JAK inhibitor therapy in patients with a prior VTE, and observe whether concurrent anticoagulation (AC) reduces this risk.</p><p><strong>Methods: </strong>We conducted a review of adults prescribed tofacitinib or upadacitinib between January 1, 2000, and June 30, 2023, with a prior history of VTE. Patient charts were reviewed for demographic data, disease type, and VTE date(s), and to verify duration of JAK inhibitor use along with any concurrent AC. VTEs following JAK inhibitor initiation were identified by International Classification of Diseases-Tenth Revision code and verified by physician documentation and imaging.</p><p><strong>Results: </strong>We identified 79 patients with a documented VTE history before initiating JAK inhibitors, 47 of whom began a JAK inhibitor with concurrent AC. Of these, 15 patients discontinued AC while receiving JAK inhibitors. In total, 5 new VTE events were observed during 55.42 patient-years of JAK inhibitor treatment without concurrent AC (9.0 events per 100 patient-years), while no new VTE events occurred during 65.2 patient-years of JAK inhibitor treatment with concurrent AC, demonstrating a lower risk of recurrent VTE (P = .020).</p><p><strong>Conclusions: </strong>These results suggest that for patients with a prior VTE history there is a high risk for recurrent VTE while receiving JAK inhibitors. Concurrent use of AC with JAK inhibitors appears to be protective against recurrent VTEs in this population.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"725-732"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis.","authors":"Anja Poulsen, Marta Sorokina Alexdóttir, Lene Buhl Riis, Martin Pehrsson, Lars Tue Sørensen, Peter-Martin Krarup, Anne-Christine Bay-Jensen, Morten A Karsdal, Ryan W Stidham, Johan Burisch, Joachim Høg Mortensen, Jakob Benedict Seidelin","doi":"10.1093/ibd/izae244","DOIUrl":"10.1093/ibd/izae244","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response.</p><p><strong>Methods: </strong>We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone.</p><p><strong>Conclusions: </strong>Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"751-762"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIP4IBD: An Easy and Rapid Genotyping-by-Sequencing Assay for the Inflammatory Bowel Diseases Risk Loci.","authors":"Sare Verstockt, Laurens Hannes, Deborah Sarah Jans, Stephanie Deman, Erika Souche, Ilse van der Werf, Liv Vandermeulen, Triana Lobaton, Debby Laukens, Bram Verstockt, Jeroen Van Houdt, Alexander Hoischen, Séverine Vermeire, Isabelle Cleynen","doi":"10.1093/ibd/izae289","DOIUrl":"10.1093/ibd/izae289","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel diseases (IBD) are polygenic, with many genetic variants contributing to disease risk. Knowing the genotype of specific variants or calculating a combined genetic risk score benefits translational and functional research. To address this, we developed MIP4IBD, a flexible and cost-effective genotyping-by-sequencing assay using molecular inversion probes (MIPs).</p><p><strong>Methods: </strong>The assay targets 463 IBD risk variants, and 77 additional relevant variants. Molecular inversion probes capture and library preparation were optimized using 15 IBD DNA samples, comparing genotypes with immunochip. A custom GitHub pipeline was created for data processing, performance testing, and genotype calling. The final design was validated on a larger scale (149 IBD patients, 104 non-IBD controls, and 3 external cell lines), incorporating post hoc quality control criteria.</p><p><strong>Results: </strong>The assay achieved a 3.5-day turnaround time at €15 per sample with optimal sample throughput, demonstrating a 92.6% success rate in variant capture and genotype concordance rates of 99.3% and 99.6% with Infinium Global Screening Array24 BeadChip and WGS, respectively. A downstream application involved the calculation of a weighted IBD polygenic risk score (PRS), which was significantly higher in IBD patients than controls (mean 0.42 vs -0.49, P = 1.95E-11). Individuals in the highest PRS quartile had a 15.7-fold (95% CI: 6.5-38.3) risk of developing IBD and an earlier age of onset (26 vs 37 years, P = 0.02), compared to the lowest quartile.</p><p><strong>Conclusions: </strong>MIP4IBD is a validated, scalable genotyping assay targeting IBD risk loci, with an integrated bioinformatics pipeline from sequencing data to genotypes and PRS calculation. Its cost-effectiveness and flexibility for additional variants make it particularly appealing for translational and clinical applications.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"786-799"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Toward Transmural Healing in Pediatric Crohn's Disease.","authors":"Sara Lega, Matteo Bramuzzo","doi":"10.1093/ibd/izae224","DOIUrl":"10.1093/ibd/izae224","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"891-892"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.","authors":"Salvatore Oliva, Silvio Veraldi, Giusy Russo, Marina Aloi, Fernando Rizzello, Paolo Gionchetti, Patrizia Alvisi, Flavio Labriola, Maurizio Vecchi, Pini Eidler, Luca Elli, Nikolas Dussias, Gian Eugenio Tontini, Carlo Calabrese","doi":"10.1093/ibd/izae052","DOIUrl":"10.1093/ibd/izae052","url":null,"abstract":"<p><strong>Background: </strong>Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults.</p><p><strong>Methods: </strong>In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups.</p><p><strong>Results: </strong>One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures.</p><p><strong>Conclusions: </strong>PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"636-646"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tofacitinib Does Not Impair Sperm Quality in Men With Ulcerative Colitis.","authors":"Anne Grosen, Emanuelle Bellaguarda, Ingela Liljeqvist-Soltic, Anne-Bine Skytte, Stephen B Hanauer, Jens Kelsen","doi":"10.1093/ibd/izae195","DOIUrl":"10.1093/ibd/izae195","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"882-884"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}