Safety of fecal microbiota, live-jslm (REBYOTA^™) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials.

IF 4.2 3区医学 Therapeutic Advances in Gastroenterology Pub Date : 2023-01-01 DOI:10.1177/17562848231174277

Christine Lee, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Paul Feuerstadt, Sahil Khanna, Robert Orenstein, Erik R Dubberke

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引用次数: 8

Abstract

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.

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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

背景:以微生物群为基础的治疗可降低复发性艰难梭菌感染(rcdi)的发生率，但扩大患者可及性和保护公众健康所需的前瞻性安全性数据收集有限。目的:我们提供来自5项前瞻性临床试验的累积安全性数据，评估粪便微生物群，活jslm (RBL) -美国食品和药物管理局批准的第一个基于微生物群的活生物治疗产品-预防成人rCDI。设计:RBL的综合安全性分析包括3个II期试验(PUNCH CD、PUNCH CD2、PUNCH Open-Label)和2个III期试验(PUNCH CD3、PUNCH CD3- ols)。方法:试验参与者至少18岁，有记录的rCDI，在RBL治疗前完成了标准护理抗生素治疗。根据试验设计，指定的研究治疗方案是直肠给药一剂或两剂RBL(或安慰剂)。在五项试验中的四项中，RBL或安慰剂治疗后8周内CDI复发的参与者有资格接受开放标签RBL治疗。治疗后出现的不良事件(teae)记录在最后一次研究治疗后至少6个月;在PUNCH CD2和PUNCH开放标签试验中，分别在12个月和24个月收集teae和严重teae。结果:在5项试验中，978名参与者接受了至少一剂RBL(指定治疗或复发后)，83名参与者仅接受安慰剂。60.2%的安慰剂组参与者和66.4%的RBL组参与者报告了teae。仅RBL组的腹痛、恶心和肠胃胀气明显高于安慰剂组。大多数teae的严重程度为轻度或中度，并且最常与先前存在的疾病有关。没有报告的感染病原被追踪到RBL。可能危及生命的teae很少发生(占参与者的3.0%)。结论:在五项临床试验中，RBL在成年rCDI患者中耐受性良好。总的来说，这些数据一致地证明了RBL的安全性。

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来源期刊

Therapeutic Advances in Gastroenterology Medicine-Gastroenterology

自引率

2.40%

发文量

103

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.