Chey W D, Dove L S, Andrae D A, Covington P S
University of Michigan, Ann Arbor, MI, USA.
Former employee of Furiex Pharmaceuticals, Inc., an affiliate of Allergan plc, Parsippany, NJ, USA.
Aliment Pharmacol Ther. 2017 May;45(10):1319-1328. doi: 10.1111/apt.14031. Epub 2017 Mar 22.
The mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, eluxadoline, is licensed in the USA for the treatment of irritable bowel syndrome with diarrhoea (IBS-D), based on the results of two large Phase 3 clinical trials.
To understand the time course of treatment benefits with eluxadoline by comparing responder rates over the first month of treatment with responder rates over longer treatment intervals.
In this post hoc analysis of two Phase 3 studies, composite and adequate relief (AR) responder rates were calculated over month 1 and patients were stratified by their responder status. Cumulative counts over subsequent intervals (months 1-3, months 1-6, months 2 through 6) were tallied.
The studies randomised 2428 patients. Over month 1, 24.6%, 22.8% and 12.5% of patients were composite responders with eluxadoline 100 mg, eluxadoline 75 mg and placebo respectively. For month 1 responders, 77.8% and 81.5% (over months 1-3) and 70.7% and 73.9% (over months 1-6) showed a continuous response with eluxadoline 100 mg and 75 mg respectively. [Correction added on 5 April 2017, after first online publication: The percentage for the responders over months 1-3 was previously wrong and has been corrected.] Of the month 1 nonresponders, <20% showed a response over months 1-3 or months 1-6. Similar results were seen for the analysis of proportions of AR responders over these time intervals.
Over two-thirds of patients who respond over the first month retain a positive response over 6 months of treatment with eluxadoline, indicating that early clinical response to eluxadoline is associated with sustained benefits for up to 6 months in patients with IBS-D.
μ-阿片受体和κ-阿片受体混合激动剂及δ-阿片受体拮抗剂埃卢多啉，基于两项大型3期临床试验的结果，在美国被批准用于治疗腹泻型肠易激综合征（IBS-D）。
通过比较治疗第一个月的缓解率与更长治疗期的缓解率，了解埃卢多啉治疗获益的时间进程。
在两项3期研究的这项事后分析中，计算第1个月的综合及充分缓解（AR）缓解率，并根据缓解状态对患者进行分层。统计后续时间段（第1 - 3个月、第1 - 6个月、第2至6个月）的累积计数。
研究共随机纳入2428例患者。在第1个月，接受100 mg埃卢多啉、75 mg埃卢多啉和安慰剂治疗的患者中，综合缓解率分别为24.6%、22.8%和12.5%。对于第1个月有反应的患者，接受100 mg和75 mg埃卢多啉治疗的患者中，分别有77.8%和81.5%（第1 - 3个月期间）以及70.7%和73.9%（第1 - 6个月期间）呈现持续反应。[2017年4月5日首次在线发表后添加更正：第1 - 3个月有反应患者的百分比之前有误，现已更正。]在第1个月无反应的患者中，不足20%在第1 - 3个月或第1 - 6个月期间出现反应。在这些时间段对AR缓解者比例的分析中也观察到类似结果。
在第一个月有反应的患者中，超过三分之二在接受埃卢多啉治疗6个月期间保持阳性反应，这表明埃卢多啉的早期临床反应与IBS-D患者长达6个月的持续获益相关。
