INTRODUCTION Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). DISCUSSION Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

中文翻译：

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利那洛肽在减少腹胀、不适和疼痛等腹部症状方面的功效：使用新型腹部评分系统的 3B 期试验。

简介 利那洛肽可改善便秘型肠易激综合征 (IBS-C) 患者的腹痛和便秘。患者报告了额外的令人烦恼的腹部症状，如腹胀和不适。本研究的目的是使用新型多项目腹部评分 (AS) 评估利那洛肽缓解 IBS-C 相关腹部症状（腹胀、不适和疼痛）的功效。方法 腹痛 ≥3 级（0-10 级）的 IBS-C 患者随机接受每日 290 μg 利那洛肽或安慰剂，持续 12 周。AS 源自 IBS 症状日记 - 便秘，是最严重时腹胀、不适和疼痛的平均值（0 = 无，10 = 最严重）。主要终点是 AS 相对于基线的总体变化 (CFB)。次要终点包括使用累积分布函数和 6 周/12 周 AS 应答者评估的 12 周 AS 中的 CFB（≥6 周/12 周 AS 改善≥2 分）。结果 总体而言，614 名患者（平均年龄 46.7 岁；81% 为女性）被随机分组​​。所有预先指定的终点均显示利那洛肽与安慰剂相比具有显着益处。利那洛肽的平均总体 CFB AS 降低为 -1.9，而安慰剂为 -1.2（P < 0.0001）；利那洛肽的 6 周/12 周 AS 反应率为 40.5%，而安慰剂为 23.4%（比值比 = 2.2 [95% 置信区间，1.55-3.12；P < 0.0001]）。腹泻是最常见的治疗引起的不良事件（利那洛肽 = 4.6%，安慰剂 = 1.6%）。讨论 与安慰剂相比，利那洛肽显着减轻了对 IBS-C 患者重要的多种腹部症状（腹胀、不适和疼痛），通过新颖的多项目 AS 进行测量。AS 源自《IBS 症状-便秘日记》，应考虑在未来的 IBS-C 临床研究中使用，以衡量传统终点之外具有临床意义的改善。