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.

中文翻译：

---

粪便微生物群 live-jslm (REBYOTA™) 在复发性艰难梭菌感染个体中的安全性：来自五项前瞻性临床试验的数据。

背景 基于微生物群的治疗可降低艰难梭菌感染 (rCDI) 的复发率，但扩大患者可及性和保护公众健康所需的前瞻性收集的安全数据有限。目标 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 live-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——用于预防成人 rCDI。设计综合安全性分析包括 RBL 的三个 II 期试验（PUNCH CD、PUNCH CD2、PUNCH Open-Label）和两个 III 期试验（PUNCH CD3、PUNCH CD3-OLS）。方法 试验参与者年龄至少 18 岁，有 rCDI 记录，在 RBL 治疗前完成了标准护理抗生素治疗。指定的研究治疗方案是直肠给药一剂或两剂 RBL（或安慰剂），具体取决于试验设计。在五项试验中的四项中，RBL 或安慰剂给药后 8 周内出现 CDI 复发的参与者有资格接受开放标签 RBL 治疗。在最后一次研究治疗后至少 6 个月内记录治疗引起的不良事件 (TEAE)；在 PUNCH CD2 和 PUNCH 开放标签试验中，分别收集了 12 个月和 24 个月的 TEAE 和严重 TEAE。结果 在五项试验中，978 名参与者至少接受了一剂 RBL（指定治疗或复发后），83 名参与者仅接受安慰剂。仅安慰剂参与者中 60.2% 和仅 RBL 参与者中 66.4% 报告了 TEAE。与仅安慰剂组相比，仅 RBL 组中仅腹痛、恶心和肠胃气胀明显更高。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。尚无致病病原体可追溯到 RBL 的感染报告。潜在危及生命的 TEAE 并不常见（占参与者的 3.0%）。结论 在五项临床试验中，RBL 在患有 rCDI 的成人中具有良好的耐受性。总的来说，这些数据一致证明了 RBL 的安全性。