Krause Richard, Ameen Vanessa, Gordon Susan H, West Marquita, Heath Amy T, Perschy Teresa, Carter Eric G
ClinSearch, Chattanooga, Tennessee, USA.
Am J Gastroenterol. 2007 Aug;102(8):1709-19. doi: 10.1111/j.1572-0241.2007.01282.x. Epub 2007 May 17.
Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate.
705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements.
The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; P< or = 0.02). Results were similar for the average adequate relief rate (treatment effects > or =12%, P< or = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae.
Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.
阿洛司琼适用于对传统治疗反应欠佳的慢性、重度腹泻型肠易激综合征（d-IBS）女性患者。便秘是阿洛司琼治疗最常见的不良事件。在一项随机、双盲、安慰剂对照研究（S3B30040）中评估了多种给药方案，以确定疗效、耐受性并评估便秘发生率。
705例重度d-IBS女性患者被随机分为安慰剂组、阿洛司琼0.5mg每日一次组、1mg每日一次组或1mg每日两次组，治疗12周。主要终点是在7分李克特整体改善量表（GIS）上第12周有反应者（IBS症状有中度或显著改善的患者）的比例。次要终点是IBS疼痛和不适充分缓解的平均发生率以及肠道症状的改善情况。
与安慰剂组相比，所有阿洛司琼组在第12周（主要时间点）GIS有反应者的比例显著更高（安慰剂组、0.5mg、1mg每日一次和1mg每日两次阿洛司琼组分别为54/176 [30.7%]、90/177 [50.8%]、84/175 [48%]和76/177 [42.9%]；P≤0.02）。平均充分缓解率的结果相似（治疗效果≥12%，P≤0.038）。所有阿洛司琼组的肠道症状均有改善。便秘是最常见的不良事件（0.5mg、1mg每日一次和1mg每日两次组的患者分别为9%、16%和19%）。0.5mg组发生1例肠梗阻和1例缺血性结肠炎，1mg每日两次组发生1例粪便嵌塞。所有事件均为自限性，且无后遗症。
阿洛司琼0.5mg和1mg每日一次以及1mg每日两次在使重度d-IBS女性患者的IBS症状整体改善、IBS疼痛和不适充分缓解以及肠道症状改善方面有效。较低的给药方案导致便秘发生率降低。
