Ohad Atia, Chagit Friss, Gili Focht, Ramit Magen Rimon, Natan Ledderman, Amir Ben-Tov, Yiska Loewenberg Weisband, Eran Matz, Yuri Gorelik, Yehuda Chowers, Iris Dotan, Dan Turner
{"title":"Durability of Adalimumab and Infliximab in Children With Crohn's Disease: A Nationwide Comparison From the epi-IIRN Cohort.","authors":"Ohad Atia, Chagit Friss, Gili Focht, Ramit Magen Rimon, Natan Ledderman, Amir Ben-Tov, Yiska Loewenberg Weisband, Eran Matz, Yuri Gorelik, Yehuda Chowers, Iris Dotan, Dan Turner","doi":"10.1093/ibd/izad301","DOIUrl":"10.1093/ibd/izad301","url":null,"abstract":"<p><strong>Background: </strong>In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy.</p><p><strong>Methods: </strong>We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models.</p><p><strong>Results: </strong>Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4).</p><p><strong>Conclusion: </strong>Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402664","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":"The Clinical Interpretation of Cluster Trials.","authors":"Pavel S Roshanov, Guangyong Zou, Reena Khanna","doi":"10.1093/ibd/izae256","DOIUrl":"https://doi.org/10.1093/ibd/izae256","url":null,"abstract":"<p><p>Cluster-randomized trials randomize entire groups of participants, instead of individual participants, to different treatment arms. For certain interventions (eg, institutional policies, processes of care, treatment algorithms), these designs protect against contamination between study arms. However, cluster trials are logistically complex to implement and have unique vulnerabilities that must be evaluated for accurate interpretation. Here, we provide a general overview of the design and statistical issues in cluster trials to facilitate their interpretation by clinicians.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568356","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}
Jean-Frédéric Colombel, María D Martín-Arranz, Brigitta Brinkman, Meijian Guan, Amy Hart, Christopher Gasink
{"title":"HLA-DQA1*05 Not Associated With Ustekinumab Loss of Response and Antidrug Antibodies in Ulcerative Colitis and Crohn's Disease Patients.","authors":"Jean-Frédéric Colombel, María D Martín-Arranz, Brigitta Brinkman, Meijian Guan, Amy Hart, Christopher Gasink","doi":"10.1093/ibd/izad273","DOIUrl":"10.1093/ibd/izad273","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459761","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}
Sudheer K Vuyyuru, Christopher Ma, Tanmay Sharma, Tran M Nguyen, Talat Bessissow, Neeraj Narula, Siddharth Singh, Florian Rieder, Vipul Jairath
{"title":"Characteristics of Interventional Trials for Patients Living With Intestinal Stoma Registered in ClinicalTrials.gov With a Focus on Inflammatory Bowel Disease.","authors":"Sudheer K Vuyyuru, Christopher Ma, Tanmay Sharma, Tran M Nguyen, Talat Bessissow, Neeraj Narula, Siddharth Singh, Florian Rieder, Vipul Jairath","doi":"10.1093/ibd/izad293","DOIUrl":"10.1093/ibd/izad293","url":null,"abstract":"<p><strong>Background: </strong>This systematic review was performed to characterize the landscape of research conducted in patients with intestinal stoma (IS) and highlight unmet needs for clinical research in Crohn's disease (CD) and IS.</p><p><strong>Methods: </strong>We searched ClinicalTrials.gov from inception to May 25, 2022, to identify clinical trials assessing interventions in patients with an IS, as well as those with an IS and CD. Studies were grouped according to type of intervention. We excluded observational studies with no treatment arm.</p><p><strong>Results: </strong>A total of 253 studies were included in the final analysis. Most studies investigated devices (n = 122 [48.2%]), or surgical procedures (n = 63 [24.9%]), followed by behavioral interventions (n = 30 [11.8%]), drugs (n = 20 [7.9%]), dietary interventions (n = 2 [0.8%]), skin care products (n = 2 0.8%]), and others (n = 14 [5.5%]). A total of 50.9% (n = 129) of studies had completed recruitment, enrolling 11 116 participants. Only 6 studies (surgery: n = 3; physiological studies: n = 2; drugs: n = 1) exclusively included patients with inflammatory bowel disease (IBD), and 16 studies commented that patients with IBD were excluded in their eligibility criteria. No study assessed efficacy of drugs in patients with CD and IS. Approximately one-quarter of studies (n = 65 of 253) included quality of life as an outcome measure.</p><p><strong>Conclusion: </strong>There is a paucity of research in IBD patients with IS, with the majority focusing on devices and surgical procedures. There have been no drug trials evaluating efficacy in patients with CD and IS. There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884895","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}
Patrizia Alvisi, Simona Faraci, Luca Scarallo, Marco Congiu, Matteo Bramuzzo, Maria Teresa Illiceto, Serena Arrigo, Claudio Romano, Giovanna Zuin, Erasmo Miele, Simona Gatti, Marina Aloi, Sara Renzo, Tamara Caldaro, Flavio Labriola, Paola De Angelis, Paolo Lionetti
{"title":"Major Abdominal Surgery for Pediatric Crohn's Disease in the Anti-TNF Era: 10-Year Analysis of Data From the IBD Registry of Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition.","authors":"Patrizia Alvisi, Simona Faraci, Luca Scarallo, Marco Congiu, Matteo Bramuzzo, Maria Teresa Illiceto, Serena Arrigo, Claudio Romano, Giovanna Zuin, Erasmo Miele, Simona Gatti, Marina Aloi, Sara Renzo, Tamara Caldaro, Flavio Labriola, Paola De Angelis, Paolo Lionetti","doi":"10.1093/ibd/izad310","DOIUrl":"10.1093/ibd/izad310","url":null,"abstract":"<p><strong>Background: </strong>The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence.</p><p><strong>Methods: </strong>We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded.</p><p><strong>Results: </strong>In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02).</p><p><strong>Conclusion: </strong>In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106063","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":"Dietary Patterns and Risk of Inflammatory Bowel Disease: A Systematic Review of Observational Studies.","authors":"Zainab Khademi, Sanaz Pourreza, Anis Amjadifar, Mohammadsadegh Torkizadeh, Farshad Amirkhizi","doi":"10.1093/ibd/izad297","DOIUrl":"10.1093/ibd/izad297","url":null,"abstract":"<p><strong>Background: </strong>The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Dietary patterns may be associated with odds of this disease. Although previous reviews have attempted to summarize the evidence in this field, the growing body of investigations prompted us to conduct an updated comprehensive systematic review.</p><p><strong>Methods: </strong>We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to evaluate the association between dietary patterns before disease onset and the risk of IBD. PubMed, SCOPUS, and Web of Science were searched using structured keywords up to November 20, 2023.</p><p><strong>Results: </strong>Twenty-four publications (13 case-control, 1 nested case-control, and 10 cohort studies) were included in this review. The sample size of these studies ranged from 181 to 482 887 subjects. The findings were inconsistent across the included studies, showing inverse, direct, or no association between different dietary patterns and the risk of IBD.</p><p><strong>Conclusions: </strong>This review provides comprehensive data on the link between dietary patterns prior to IBD diagnosis and risk of this condition. The explicit finding of present review is the extent gap in our knowledge in this field. Therefore, large-scale, high-quality studies are warranted to improve our understanding of the relationship between dietary patterns and IBD risk.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106052","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}
Lev Krasnovsky, Andrew T Weber, Victoria Gershuni, Erica Pettke, James D Lewis
{"title":"Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.","authors":"Lev Krasnovsky, Andrew T Weber, Victoria Gershuni, Erica Pettke, James D Lewis","doi":"10.1093/ibd/izad304","DOIUrl":"10.1093/ibd/izad304","url":null,"abstract":"<p><strong>Background: </strong>Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2.</p><p><strong>Results: </strong>Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes.</p><p><strong>Conclusions: </strong>Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541875","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":"Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.","authors":"Dai Ishikawa, Xiaochen Zhang, Kei Nomura, Tomoyoshi Shibuya, Mariko Hojo, Makoto Yamashita, Satoshi Koizumi, Fuhito Yamazaki, Susumu Iwamoto, Masato Saito, Keisuke Kunigo, Ryosuke Nakano, Nakayuki Honma, Itaru Urakawa, Akihito Nagahara","doi":"10.1093/ibd/izae080","DOIUrl":"10.1093/ibd/izae080","url":null,"abstract":"<p><strong>Background: </strong>The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.</p><p><strong>Methods: </strong>Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies.</p><p><strong>Results: </strong>Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling.</p><p><strong>Conclusions: </strong>This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908795","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}