Lembo Anthony J, Covington Paul S, Dove Leonard S, Andrae David A
Harvard Medical School, Boston, MA, USA.
Former employee of Furiex Pharmaceuticals, Inc., an affiliate of Allergan plc, Madison, NJ, USA.
Neurogastroenterol Motil. 2020 Apr;32(4):e13774. doi: 10.1111/nmo.13774. Epub 2020 Jan 27.
Recurring abdominal pain is a characteristic and often unpredictable and debilitating symptom of irritable bowel syndrome with diarrhea (IBS-D). Measuring the effects of IBS-D treatments on abdominal pain remains a significant challenge in clinical trials. Here, we aimed to examine the effect of eluxadoline through various post hoc analyses.
Data from two eluxadoline Phase 3 trials were pooled over 26 weeks, comparing eluxadoline 100 mg twice daily to placebo. Worst abdominal pain (WAP) was measured daily on a 0-10 scale. WAP responder criteria were prospectively defined as a ≥30% improvement in daily WAP score on ≥50% of days. Pairwise, two-sided Cochran-Mantel-Haenszel tests assessed treatment effects. Cumulative distribution functions were used to plot WAP response rates using variations on the response criteria.
Of 1615 patients with IBS-D (66% female, mean age 46 years), 806 received eluxadoline and 809 received placebo; 48.3% and 44.0% were WAP responders (≥30% improvement), respectively (P value not significant). When the response threshold was increased to 50% daily WAP improvement from baseline, a significantly greater percentage of eluxadoline-treated patients versus placebo-treated patients were WAP responders (38.7% vs 32.5%, respectively; P = .009). At Week 26, average WAP changes from baseline were -3.4 and -3.0 points, respectively (P = .002).
Despite small effect sizes, eluxadoline demonstrated consistent and sustained improvement in WAP compared to placebo across a range of prospective and post hoc analyses. Assessing WAP response across a range of measures is important for fully understanding a treatment's efficacy.
反复出现的腹痛是腹泻型肠易激综合征（IBS-D）的一个特征性症状，通常不可预测且使人虚弱。在临床试验中，衡量IBS-D治疗对腹痛的影响仍然是一项重大挑战。在此，我们旨在通过各种事后分析来研究埃卢多啉的效果。
将两项埃卢多啉3期试验的数据汇总，为期26周，比较每日两次服用100毫克埃卢多啉与安慰剂的效果。每天用0至10分的量表测量最严重腹痛（WAP）。WAP缓解标准预先定义为在≥50%的天数里每日WAP评分改善≥30%。采用双侧Cochran-Mantel-Haenszel检验评估治疗效果。使用累积分布函数，根据缓解标准的变化绘制WAP缓解率。
在1615例IBS-D患者中（66%为女性，平均年龄46岁），806例接受埃卢多啉治疗，809例接受安慰剂治疗；WAP缓解者（改善≥30%）分别为48.3%和44.0%（P值无统计学意义）。当缓解阈值从基线提高到每日WAP改善50%时，接受埃卢多啉治疗的患者中WAP缓解者的比例显著高于接受安慰剂治疗的患者（分别为38.7%和32.5%；P = 0.009）。在第26周时，WAP较基线的平均变化分别为-3.4分和-3.0分（P = 0.002）。
尽管效应量较小，但在一系列前瞻性和事后分析中，与安慰剂相比埃卢多啉在WAP方面显示出持续且稳定的改善。通过一系列测量评估WAP缓解情况对于全面理解治疗效果很重要。
