Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.12.040
Pankaj J. Pasricha, Nicholas J. Talley, Linda Nguyen, Thomas Abell, John Furness, Mark Pimentel
No Abstract
{"title":"Names matter: a call to neurogastroenterologists to examine how we can improve the nomenclature we use to describe the disorders our patients experience","authors":"Pankaj J. Pasricha, Nicholas J. Talley, Linda Nguyen, Thomas Abell, John Furness, Mark Pimentel","doi":"10.1053/j.gastro.2024.12.040","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.040","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2025.01.230
Amber L. Alhadeff, Brian J. DeBosch
No Abstract
{"title":"A new tool to study the DREADDed peripheral nervous system","authors":"Amber L. Alhadeff, Brian J. DeBosch","doi":"10.1053/j.gastro.2025.01.230","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.230","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"10 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.09.010
Samuel Asfaha, Nicola L. Jones
{"title":"Reevaluating Stemness in the Intestinal Crypt","authors":"Samuel Asfaha, Nicola L. Jones","doi":"10.1053/j.gastro.2024.09.010","DOIUrl":"10.1053/j.gastro.2024.09.010","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"168 2","pages":"Page 417"},"PeriodicalIF":25.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.09.030
Jessica R. Allegretti , Colleen R. Kelly , Thomas Louie , Monika Fischer , Susy Hota , Bharat Misra , Nick W. Van Hise , Eugene Yen , Jeffrey S. Bullock , Michael Silverman , Ian Davis , Sarah K. McGill , Darrell S. Pardi , Robert Orenstein , Ari Grinspan , Najwa El-Nachef , Paul Feuerstadt , Thomas J. Borody , Sahil Khanna , Shrish Budree , Zain Kassam
Background & Aims
Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.
Methods
We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 1011 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24.
Results
A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction–based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups.
Conclusions
CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133)
{"title":"Safety and Tolerability of CP101, a Full-Spectrum, Oral Microbiome Therapeutic for the Prevention of Recurrent Clostridioides difficile Infection: A Phase 2 Randomized Controlled Trial","authors":"Jessica R. Allegretti , Colleen R. Kelly , Thomas Louie , Monika Fischer , Susy Hota , Bharat Misra , Nick W. Van Hise , Eugene Yen , Jeffrey S. Bullock , Michael Silverman , Ian Davis , Sarah K. McGill , Darrell S. Pardi , Robert Orenstein , Ari Grinspan , Najwa El-Nachef , Paul Feuerstadt , Thomas J. Borody , Sahil Khanna , Shrish Budree , Zain Kassam","doi":"10.1053/j.gastro.2024.09.030","DOIUrl":"10.1053/j.gastro.2024.09.030","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Recurrent <em>Clostridioides difficile</em> infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.</div></div><div><h3>Methods</h3><div>We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 10<sup>11</sup> colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24.</div></div><div><h3>Results</h3><div>A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction–based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; <em>P</em> = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; <em>P</em> = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups.</div></div><div><h3>Conclusions</h3><div>CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, Number NCT03110133)</div></div>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"168 2","pages":"Pages 357-366.e3"},"PeriodicalIF":25.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.10.009
Virginia Solitano , Malcolm Hogan , Siddharth Singh , Silvio Danese , Laurent Peyrin-Biroulet , Guangyong Zou , Yuhong Yuan , Bruce E. Sands , Brian G. Feagan , Parambir S. Dulai , Neeraj Narula , Christopher Ma , Vipul Jairath
Background & Aims
Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn’s disease trials.
Methods
We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn’s disease (2010–2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates.
Results
Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%–32%) and 10% (95% CI, 8%–14%), respectively, and 32% (95% CI, 23%–42%) and 22% (95% CI, 14%–33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%–35%) and 11% (95% CI, 8%–15%) respectively, and 26% (95% CI, 20%–33%) and 10% (95% CI, 8%–14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%–48%) and 32% (95% CI, 24%–40%), respectively, and 29% (95% CI, 24%–34%) and 16% (95% CI, 13%–21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn’s Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance.
Conclusions
Patient- and trial-level characteristics influence placebo rates in Crohn’s disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.
{"title":"Placebo Rates in Crohn’s Disease Randomized Clinical Trials: An Individual Patient Data Meta-Analysis","authors":"Virginia Solitano , Malcolm Hogan , Siddharth Singh , Silvio Danese , Laurent Peyrin-Biroulet , Guangyong Zou , Yuhong Yuan , Bruce E. Sands , Brian G. Feagan , Parambir S. Dulai , Neeraj Narula , Christopher Ma , Vipul Jairath","doi":"10.1053/j.gastro.2024.10.009","DOIUrl":"10.1053/j.gastro.2024.10.009","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn’s disease trials.</div></div><div><h3>Methods</h3><div>We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn’s disease (2010–2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates.</div></div><div><h3>Results</h3><div>Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%–32%) and 10% (95% CI, 8%–14%), respectively, and 32% (95% CI, 23%–42%) and 22% (95% CI, 14%–33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%–35%) and 11% (95% CI, 8%–15%) respectively, and 26% (95% CI, 20%–33%) and 10% (95% CI, 8%–14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%–48%) and 32% (95% CI, 24%–40%), respectively, and 29% (95% CI, 24%–34%) and 16% (95% CI, 13%–21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn’s Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance.</div></div><div><h3>Conclusions</h3><div>Patient- and trial-level characteristics influence placebo rates in Crohn’s disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.</div></div>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"168 2","pages":"Pages 344-356"},"PeriodicalIF":25.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.09.037
James Cheng-Chung Wei, Poi Kuo, Qi Mei
{"title":"Methodology of Study on GLP-1 Receptor Agonists and Hepatocellular Carcinoma Risk","authors":"James Cheng-Chung Wei, Poi Kuo, Qi Mei","doi":"10.1053/j.gastro.2024.09.037","DOIUrl":"10.1053/j.gastro.2024.09.037","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"168 2","pages":"Page 422"},"PeriodicalIF":25.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1053/j.gastro.2024.06.041
Avinash Tiwari
{"title":"CHRONICLE Trial: How Cool Is Cold Snaring for Endoscopic Mucosal Resection?","authors":"Avinash Tiwari","doi":"10.1053/j.gastro.2024.06.041","DOIUrl":"10.1053/j.gastro.2024.06.041","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"168 2","pages":"Pages 425-426"},"PeriodicalIF":25.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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