Quigley Eamonn M M, Markinson Louise, Stevenson Alex, Treasure F Peter, Lacy Brian E
Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA.
Houston Methodist Gastroenterology Associates, Houston, Texas, USA.
Aliment Pharmacol Ther. 2023 Jan;57(1):81-93. doi: 10.1111/apt.17310. Epub 2022 Nov 11.
MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS).
To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS-C) or diarrhoea (IBS-D) METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients aged 18-70 years in two parallel cohorts (IBS-C; IBS-D) were randomised (1:1) to MRx1234 or placebo for 8 weeks. The primary efficacy endpoint was overall responder rate-a composite of improved bowel habit (IBS-C: stool frequency; IBS-D: stool consistency) and abdominal pain intensity-for ≥50% of the treatment period in each cohort. Statistical testing was at a one-sided 0.10 significance level.
Of 366 randomised patients (164 IBS-C; 202 IBS-D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS-C (25.0% vs. 17.1%) and IBS-D (23.4% vs. 17.8%) cohorts. Similar results were observed in the additional combined cohort analysis (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS-C, IBS-D and combined cohorts, while improvements in abdominal pain were observed in each cohort. The safety profile of MRx1234 was similar to placebo.
MRx1234 has the potential to become a novel, safe treatment option for patients with IBS-C or IBS-D, and for those who have mixed symptoms or transition between subtypes.
gov #NCT03721107.
MRx1234是一种含有嗜氢布劳特氏菌菌株的活体生物治疗产品。它正处于开发阶段，用于治疗肠易激综合征（IBS）。
评估MRx1234在以便秘为主型肠易激综合征（IBS-C）或腹泻为主型肠易激综合征（IBS-D）患者中的疗效和安全性。
我们进行了一项多中心、随机、双盲、安慰剂对照的2期试验。将两个平行队列（IBS-C；IBS-D）中年龄在18至70岁的患者随机（1:1）分为接受MRx1234或安慰剂治疗8周。主要疗效终点是总体缓解率，即每个队列中在至少50%的治疗期内肠道习惯改善（IBS-C：排便频率；IBS-D：粪便稠度）和腹痛强度改善的综合指标。统计检验的单侧显著性水平为0.10。
在366例随机分组的患者中（164例IBS-C；202例IBS-D），365例接受了任何研究药物治疗（177例接受MRx1234，188例接受安慰剂）。从数字上看，尽管在统计学上没有显著差异，但在IBS-C队列（25.0%对17.1%）和IBS-D队列（23.4%对17.8%）中，接受MRx1234的总体缓解患者比接受安慰剂的更多。在额外的合并队列分析中也观察到了类似结果（24.1%对17.5%；p = 0.063）。对于主要终点的各个组成部分，在IBS-C、IBS-D和合并队列中，接受MRx1234的患者报告肠道习惯改善的人数显著多于接受安慰剂的患者，同时在每个队列中均观察到腹痛有所改善。MRx1234的安全性与安慰剂相似。
MRx1234有可能成为IBS-C或IBS-D患者以及有混合症状或在亚型之间转换的患者的一种新型、安全的治疗选择。
美国国立医学图书馆临床试验注册平台编号#NCT03721107 。
