复发性感染个体中粪便微生物群、活-jslm（REBYOTA）的安全性：来自五项前瞻性临床试验的数据。

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

作者信息

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

机构信息

Medical Microbiologist and Researcher, Island Health, Clinical Professor, Department of Pathology and Laboratory Medicine, The University of British Columbia Faculty of Medicine, Vancouver, BC V6T 1Z3, Canada.

Island Medical Program University of British Columbia, University of Victoria, Victoria, BC, Canada.

出版信息

Therap Adv Gastroenterol. 2023 Jun 12;16:17562848231174277. doi: 10.1177/17562848231174277. eCollection 2023.

DOI:10.1177/17562848231174277

PMID:37333464

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10272687/

Abstract

BACKGROUND

Microbiota-based treatments reduce the incidence of recurrent 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.

摘要

背景

基于微生物群的治疗可降低复发性感染（rCDIs）的发生率，但为扩大患者准入范围和保护公众健康所需的前瞻性收集的安全性数据有限。

目的

我们提供了五项前瞻性临床试验的累积安全性数据，这些试验评估了粪便微生物群、活菌制剂（RBL）——美国食品药品监督管理局批准的首个基于微生物群的活菌生物治疗产品——用于预防成人复发性艰难梭菌感染（rCDI）的效果。

设计

综合安全性分析包括三项RBL的II期试验（PUNCH CD、PUNCH CD2、PUNCH开放标签试验）和两项III期试验（PUNCH CD3、PUNCH CD3 - OLS）。

方法

试验参与者年龄至少18岁，有记录的rCDI，在接受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经直肠给予一剂或两剂RBL（或安慰剂）。在五项试验中的四项中，在给予RBL或安慰剂后8周内出现CDI复发的参与者有资格接受开放标签的RBL治疗。在最后一次研究治疗后至少记录6个月的治疗中出现的不良事件（TEAEs）；在PUNCH CD2和PUNCH开放标签试验中，分别在12个月和24个月收集TEAEs和严重TEAEs。

结果

在这五项试验中，978名参与者接受了至少一剂RBL（指定治疗或复发后），83名参与者仅接受了安慰剂。仅接受安慰剂的参与者中有60.2%报告了TEAEs，仅接受RBL的参与者中有66.4%报告了TEAEs。与仅接受安慰剂的组相比，仅接受RBL的组中只有腹痛、恶心和肠胃胀气显著更高。大多数TEAEs的严重程度为轻度或中度，且最常与既往疾病有关。没有报告致病病原体可追溯到RBL的感染。潜在危及生命的TEAEs很少见（占参与者的3.0%）。