Supplementary Material for: Tenapanor Improves Abdominal Symptoms Irrespective of Changes In Complete Spontaneous Bowel Movement Frequency in Adults With Irritable Bowel Syndrome With Constipation

Introduction: Tenapanor is a first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor approved by the U.S. Food and Drug Administration for adults with irritable bowel syndrome with constipation (IBS-C). Pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies examined the effects of tenapanor on abdominal symptoms independent of tenapanor’s effect on complete spontaneous bowel movement (CSBM) frequency in adults with IBS-C.

Methods: This post hoc analysis was performed for patients with no CSBMs in ≥6 of the first 12 weeks of treatment (no-CSBM subgroup). The three-item Abdominal Score (AS3; the average of weekly abdominal pain, bloating, and discomfort scores) measured abdominal symptom response in tenapanor vs. placebo. The overall change from baseline and response rate (improvement of ≥2 points or a reduction of ≥30%) in AS3 and individual abdominal scores during the 12 weeks were assessed.

Results: In the pooled safety analysis set (N = 1,382), 641 patients were classified as no-CSBM patients and 640 were included in the efficacy analysis. Among the no-CSBM subgroup, tenapanor-treated patients experienced a greater improvement in AS3 in week 12 vs. placebo-treated patients (least squares mean change, −1.74 vs. −1.29; p = 0.007), and the AS3 responder rate was higher for tenapanor (40.2% vs. 29.6%; p = 0.008). Similar improvements were displayed across individual abdominal symptom scores. Diarrhea was the most common adverse event in tenapanor-treated patients.

Conclusion: Tenapanor was observed to improve abdominal symptoms independent of its effect on bowel symptoms in adults with IBS-C.

引言：Tenapanor是一款同类首创的低吸收性肠道钠氢交换体3亚型抑制剂，已获美国食品药品监督管理局批准用于治疗成人便秘型肠易激综合征（IBS-C）。本研究汇总了2b期（NCT01923428）及3期T3MPO-1（NCT02621892）、T3MPO-2（NCT02686138）研究的数据，旨在评估Tenapanor对IBS-C成人患者腹部症状的影响，且该影响独立于其对完全自发性排便（CSBM）频率的作用。

方法：本事后分析针对治疗前12周内至少6周无CSBM的患者（无CSBM亚组）开展。采用三项腹部评分（AS3；即每周腹痛、腹胀及腹部不适评分的平均值）评估Tenapanor组与安慰剂组患者的腹部症状应答情况。同时评估12周内AS3及各项腹部症状评分的基线至终点总体变化，以及应答率（改善≥2分或降低≥30%）。

结果：在汇总安全性分析集（N=1382）中，641例患者被归类为无CSBM患者，其中640例纳入疗效分析。在无CSBM亚组中，与安慰剂组相比，Tenapanor组患者在第12周的AS3改善更显著（最小二乘均数变化：-1.74 vs. -1.29；P=0.007），且AS3应答率更高（40.2% vs. 29.6%；P=0.008）。各项腹部症状评分均观察到类似改善。腹泻是Tenapanor组最常见的不良事件。

结论：观察发现，Tenapanor可改善IBS-C成人患者的腹部症状，且该作用独立于其对肠道症状的影响。