Cash Brooks D, Lacy Brian E, Rao Tharaknath, Earnest David L
a Gastroenterology Division , University of South Alabama , Mobile , AL , USA.
b Division of Gastroenterology & Hepatology , Dartmouth-Hitchcock Medical Center , Lebanon , NH , USA.
Expert Opin Pharmacother. 2016;17(3):311-22. doi: 10.1517/14656566.2016.1118052. Epub 2015 Dec 8.
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence.
We review two recently approved therapies that focus on treating underlying pathogenic mechanisms of IBS-D: (1) the non-absorbable antibiotic rifaximin, and (2) the opioid receptor agonist/antagonist eluxadoline. We compare the safety and efficacy data emerging from rifaximin and eluxadoline registration trials with safety and efficacy data from the alosetron clinical development program.
The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles.
腹泻型肠易激综合征(IBS-D)是一种常见的功能性胃肠疾病,患者会出现腹痛、腹泻、腹胀、痉挛、肠胃气胀、排便急迫感和大便失禁等症状。
我们回顾了两种最近获批的专注于治疗IBS-D潜在致病机制的疗法:(1)不可吸收抗生素利福昔明,以及(2)阿片受体激动剂/拮抗剂埃托啡啶。我们将利福昔明和埃托啡啶注册试验中出现的安全性和有效性数据与阿洛司琼临床开发项目中的安全性和有效性数据进行了比较。
IBS-D的利福昔明和埃托啡啶临床开发项目已证明,与安慰剂相比,IBS-D的各项指标有显著改善。无法直接比较阿洛司琼、利福昔明和埃托啡啶关键试验的主要终点结果;然而,可以进行一般疗效估计,这些估计表明,与安慰剂相比,每种药物对“充分缓解”以及腹痛/大便形态综合终点的反应相似且显著更大。随着利福昔明和埃托啡啶最近在美国获批用于IBS-D,临床医生应如何使用这些药物?我们建议根据患者症状和严重程度、既往病史、作用方式、成本、可获得性、管理式医疗覆盖范围和不良事件概况依次使用这些药物。