Lacy Brian E, Chey William D, Cash Brooks D, Lembo Anthony J, Dove Leonard S, Covington Paul S
Division of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
Am J Gastroenterol. 2017 Jun;112(6):924-932. doi: 10.1038/ajg.2017.72. Epub 2017 Apr 18.
Irritable bowel syndrome with diarrhea (IBS-D) is often managed with over-the-counter therapies such as loperamide, though with limited success. This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies.
Adults with IBS-D (Rome III criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies. The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea.
A total of 2,428 patients were enrolled; 36.0% reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D symptom control with loperamide. Among patients with prior loperamide use, a greater proportion treated with eluxadoline (75 and 100 mg) were composite responders vs. those treated with placebo with inadequate prior symptom control, over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively); similar results were observed over weeks 1-26. When daily rescue loperamide use was imputed as a nonresponse day, the composite responder rate was still higher in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12 (P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal pain.
Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment, with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment.
腹泻型肠易激综合征（IBS-D）通常采用洛哌丁胺等非处方疗法进行治疗，但效果有限。本分析在两项3期研究中评估了eluxadoline对先前接受过洛哌丁胺治疗的患者的疗效。
纳入符合罗马III标准的IBS-D成年患者，并将其随机分为安慰剂组或eluxadoline组（75或100毫克），每日两次，治疗26周（IBS-3002）或52周（IBS-3001）。患者报告前一年使用洛哌丁胺的情况，并记录研究期间急救用洛哌丁胺的使用情况。主要疗效终点是腹痛同时改善且腹泻减少的复合反应患者比例。
共纳入2428例患者；36.0%报告曾使用过洛哌丁胺，其中61.8%报告先前使用洛哌丁胺时IBS-D症状控制不佳。在先前使用过洛哌丁胺的患者中，与症状控制不佳且接受安慰剂治疗的患者相比，接受eluxadoline（75和100毫克）治疗的患者在第1至12周（分别为26.3%（P=0.001）和27.0%（P<0.001）对12.7%）以及第1至26周的复合反应者比例更高；在第1至12周（P<0.001）和第1至26周（P<0.001），当将每日急救用洛哌丁胺的使用视为无反应日时，接受eluxadoline（75和100毫克）治疗的患者的复合反应率仍高于安慰剂组。不良事件包括恶心和腹痛。
Eluxadoline有效且安全地治疗IBS-D的腹痛和腹泻症状，无论患者自我报告先前使用洛哌丁胺治疗时症状控制是否良好，且无论在eluxadoline治疗期间是否将洛哌丁胺用作急救药物，其疗效和安全性相当。
