Orenstein Robert
Division of Infectious Diseases, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA.
Infect Dis Ther. 2023 Jan;12(1):1-7. doi: 10.1007/s40121-022-00714-9. Epub 2022 Nov 7.
A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioides difficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24 months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8 weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24 months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7 days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection: Durable, long-term results of RBX2660 (MP4 511833 KB).
最近发表的一篇手稿描述了一项2期开放标签研究的结果,该研究针对有两次或更多次既往艰难梭菌复发性感染(rCDI)发作的患者,对基于微生物群的活生物治疗产品RBX2660进行了研究,并描述了长达24个月的长期安全性和持续治疗成功情况。由于以往的研究通常侧重于短期临床结果,这些新数据为RBX2660的长期耐受性、安全性和有效性提供了见解。当首次评估基于微生物群的产品时,长期疗效和安全性是美国食品药品监督管理局主要关注的问题。基于微生物群的活生物治疗产品(LBPs)是治疗CDI以及其他一些胃肠道和医学疾病(其发病机制由微生物失调定义)的一种新兴方法。RBX2660是一种源自人类的、基于广泛微生物群的LBP,由从健康粪便供体获得的一群微生物组成,可能反映了健康结肠微生物群的共生性质。RBX2660通过直肠给药,不需要对接受者进行镇静或特殊准备。RBX2660直肠给药的潜在优势包括给药方便且无需任何肠道准备,这可能使身体虚弱、有吞咽问题或无法服用肠道泻药制剂的患者受益。在这项rCDI的多中心前瞻性试验中,接受RBX2660治疗8周后取得治疗成功的患者在长期随访过程中继续保持持续的临床反应,超过90%的治疗反应者在6个月、12个月和24个月时仍无CDI。接受RBX2660治疗后,治疗成功患者的肠道微生物群从失调状态恢复,变得更加多样化且与RBX2660的组成相似。微生物群的恢复在RBX2660给药后最早7天出现,并在24个月的分析期内保持稳定。在前瞻性评估期间未观察到新的不良结果,RBX2660的安全性与以往研究一致。基于临床研究,RBX2660很可能使有≥1次rCDI发作的患者或后续rCDI高危患者受益,例如患有包括肾病、心脏病或炎症性肠病等合并症的患者,或免疫功能低下的患者。基于微生物群的疗法在艰难梭菌感染中的作用:RBX2660的持久长期结果(MP4 511833 KB)