Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Division of Gastroenterology, International University of Health and Welfare Fukuoka Sanno Hospital, Fukuoka, Japan.
Clin Gastroenterol Hepatol. 2016 Jun;14(6):809-815.e1. doi: 10.1016/j.cgh.2015.10.022. Epub 2015 Oct 30.
BACKGROUND & AIMS: Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti-inflammatory drugs and PPIs simultaneously. We performed a randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury.
Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2 inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 + placebo group, n = 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 + PPI group, n = 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination.
A significantly higher proportion of subjects in the COX-2 + PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2 + placebo group (5 of 30 subjects; 16.7%; P = .04). Subjects in the COX-2 + PPI group had a significant increase in risk of small bowel injury compared with the COX-2 + placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2 + PPI group was greater than in each member of the COX-2 + placebo group (P = .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2 + PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2 + placebo group (P = .003); no such trend was found in the ileum.
In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.
一些研究报告称，同时服用非选择性非甾体抗炎药和质子泵抑制剂（PPIs）的受试者中，有 60%-80%小肠损伤发生率较高。我们进行了一项随机、双盲、对照研究，以确定质子泵抑制剂（PPIs）是否会加重非甾体抗炎药引起的小肠损伤。
57 名健康受试者被随机分为两组，一组给予环氧化酶（COX）2 抑制剂塞来昔布（200mg，每日两次）加安慰剂治疗 2 周（COX-2+安慰剂组，n=30），另一组给予塞来昔布加 PPI 雷贝拉唑（20mg，每日一次）治疗 2 周（COX-2+PPI 组，n=27）。该研究于 2012 年 10 月至 2013 年 9 月在日本的一家三级医疗中心进行。所有受试者在研究开始时和服用塞来昔布加雷贝拉唑或安慰剂 2 周后均接受胶囊内镜检查。比较两组胶囊内镜下小肠损伤（溃疡和糜烂）的发生率和数量。主要终点是第二次胶囊内镜检查时黏膜损伤的发生率。
COX-2+PPI 组有 12 名受试者（27 名中的 44.4%）发生小肠损伤，明显高于 COX-2+安慰剂组的 5 名受试者（30 名中的 16.7%；P=0.04）。与 COX-2+安慰剂组相比，COX-2+PPI 组发生小肠损伤的风险显著增加（相对风险，2.67；95%置信区间，1.08-6.58）。COX-2+PPI 组每个成员的糜烂数量均大于 COX-2+安慰剂组（P=0.02）。两组溃疡数量无差异。COX-2+PPI 组 26%的受试者发生空肠黏膜损伤，而 COX-2+安慰剂组无此趋势（P=0.003）；在回肠中未发现这种趋势。
在一项随机对照试验中，PPIs 增加了短期非甾体抗炎药引起的小肠损伤风险。UMIN 临床试验注册编号：UMIN000008883。
