普卡那肽改善便秘型肠易激综合征症状：两项3期试验的综合疗效与安全性分析结果

Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials.

作者信息

Brenner Darren M, Dorn Spencer D, Fogel Ronald P, Christie Jennifer, Laitman Adam P, Rosenberg Jonathan

机构信息

Internal Medicine-Gastroenterology, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA.

Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA.

出版信息

Int J Gen Med. 2023 Aug 25;16:3769-3777. doi: 10.2147/IJGM.S400431. eCollection 2023.

DOI:10.2147/IJGM.S400431

PMID:37649852

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10464888/

Abstract

PURPOSE

Patients with irritable bowel syndrome with constipation (IBS-C) experience abdominal pain with altered bowel movements. Plecanatide is indicated as IBS-C treatment in adults. This integrated analysis further characterizes plecanatide efficacy and safety in IBS-C.

PATIENTS AND METHODS

Data pooled from 2 identically designed phase 3 trials included adults with IBS-C randomized to plecanatide 3 mg or 6 mg, or placebo once daily for 12 weeks. A daily diary recorded stool frequency/symptoms, with abdominal pain, bloating, cramping, discomfort, fullness, and straining intensity individually rated. Overall response (primary endpoint) was defined as ≥30% improvement from baseline in average worst abdominal pain severity and increase of ≥1 complete spontaneous bowel movement, during same week (composite), for ≥6 of 12 weeks. Secondary endpoints included sustained response (overall response, plus meeting weekly composite criteria during ≥2 of last 4 treatment weeks) and changes from baseline in individual symptoms. Safety assessments included adverse event monitoring.

RESULTS

Overall, 2176 patients (74.0% female; mean [SD] age, 43.5 [14.1] years) were included in efficacy analyses (plecanatide 3 mg [n = 724], 6 mg [n = 723], placebo [n = 729]). A significantly greater percentage of patients achieved overall response with plecanatide 3 mg (25.6%) and 6 mg (26.7%) versus placebo (16.0%; both P < 0.001 vs placebo). A significantly greater percentage of patients were sustained responders with plecanatide 3 mg (24.3%) and 6 mg (25.6%) versus placebo (15.6%; both P < 0.001 vs placebo). Significant improvements from baseline in abdominal discomfort, abdominal fullness, abdominal pain, bloating, and cramping occurred as early as Week 1 (Week 2 for abdominal pain) with plecanatide and were maintained through Week 12 versus placebo. Diarrhea, the most common adverse event, occurred in 4.3% (3 mg), 4.0% (6 mg) and 1.0% (placebo) of patients, leading to study discontinuation in 1.2%, 1.4%, and 0 patients, respectively.

CONCLUSION

Plecanatide is safe and effective for treating global and individual IBS-C symptoms.

摘要

目的

便秘型肠易激综合征（IBS-C）患者会经历腹痛并伴有排便习惯改变。普卡那肽被批准用于成人IBS-C的治疗。这项综合分析进一步阐述了普卡那肽治疗IBS-C的疗效和安全性。

患者和方法

从两项设计相同的3期试验中汇总的数据包括患有IBS-C的成人，他们被随机分为接受每日一次12周的3毫克或6毫克普卡那肽或安慰剂治疗。每日日志记录大便频率/症状，并对腹痛、腹胀、绞痛、不适、饱胀感和用力强度进行单独评分。总体缓解（主要终点）定义为在12周中的≥6周内，平均最严重腹痛严重程度较基线改善≥30%，且在同一周内完全自主排便增加≥1次（综合指标）。次要终点包括持续缓解（总体缓解，加上在最后4个治疗周中的≥2周达到每周综合标准）以及各个症状较基线的变化。安全性评估包括不良事件监测。

结果

总体而言，2176例患者（74.0%为女性；平均[标准差]年龄43.5[14.1]岁）纳入疗效分析（3毫克普卡那肽组[n = 724]，6毫克普卡那肽组[n = 723]，安慰剂组[n = 729]）。与安慰剂组（16.0%）相比，3毫克（25.6%）和6毫克（26.7%）普卡那肽组达到总体缓解的患者比例显著更高（与安慰剂组相比，P均<0.001）。与安慰剂组（15.6%）相比，3毫克（24.3%）和6毫克（25.6%）普卡那肽组持续缓解的患者比例显著更高（与安慰剂组相比，P均<0.001）。使用普卡那肽治疗时，早在第1周（腹痛为第2周）腹痛不适、腹部饱胀、腹痛、腹胀和绞痛较基线就有显著改善，并持续至第12周，与安慰剂组相比。腹泻是最常见的不良事件，分别发生在4.3%（3毫克组）、4.0%（6毫克组）和1.0%（安慰剂组）的患者中，导致停药的比例分别为1.2%、1.4%和0。