Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke
{"title":"复发性艰难梭菌感染患者粪便微生物群live-jslm (REBYOTA™)的安全性:来自五项前瞻性临床试验的数据","authors":"Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke","doi":"10.1177/17562848231174277","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Microbiota-based treatments reduce the incidence of recurrent <i>Clostridioides difficile</i> infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited.</p><p><strong>Objectives: </strong>We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.</p><p><strong>Design: </strong>Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.</p><p><strong>Methods: </strong>Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively.</p><p><strong>Results: </strong>Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants).</p><p><strong>Conclusion: </strong>Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.</p>","PeriodicalId":23022,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"16 ","pages":"17562848231174277"},"PeriodicalIF":4.2000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/0d/10.1177_17562848231174277.PMC10272687.pdf","citationCount":"8","resultStr":"{\"title\":\"Safety of fecal microbiota, live-jslm (REBYOTA<sup>™</sup>) in individuals with recurrent <i>Clostridioides difficile</i> infection: data from five prospective clinical trials.\",\"authors\":\"Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke\",\"doi\":\"10.1177/17562848231174277\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Microbiota-based treatments reduce the incidence of recurrent <i>Clostridioides difficile</i> infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited.</p><p><strong>Objectives: </strong>We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.</p><p><strong>Design: </strong>Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.</p><p><strong>Methods: </strong>Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively.</p><p><strong>Results: </strong>Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants).</p><p><strong>Conclusion: </strong>Across five clinical trials, RBL was well tolerated in adults with rCDI. 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Safety of fecal microbiota, live-jslm (REBYOTA™) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials.
Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited.
Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.
Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.
Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively.
Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants).
Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.
期刊介绍：
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.
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