Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury

A Randomized, Placebo-Controlled Trial

Ema Washio, Motohiro Esaki, yuji maehata, Masashi Miyazaki, Hiroyuki Kobayashi, Hideki Ishikawa, Takanari Kitazono, Takayuki Matsumoto

研究成果: ジャーナルへの寄稿記事

46 引用 (Scopus)

抄録

Background and 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. Methods: 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. Results: 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. Conclusions: 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.

元の言語英語
ページ(範囲)809-815.e1
ジャーナルClinical Gastroenterology and Hepatology
14
発行部数6
DOI
出版物ステータス出版済み - 6 1 2016

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Proton Pump Inhibitors
Cyclooxygenase 2
Anti-Inflammatory Agents
Randomized Controlled Trials
Placebos
Celecoxib
Incidence
Wounds and Injuries
Pharmaceutical Preparations
Capsule Endoscopy
Rabeprazole
Ulcer
Cyclooxygenase 2 Inhibitors
Jejunum
Ileum
Double-Blind Method
Registries
Healthy Volunteers
Japan
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

これを引用

Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury : A Randomized, Placebo-Controlled Trial. / Washio, Ema; Esaki, Motohiro; maehata, yuji; Miyazaki, Masashi; Kobayashi, Hiroyuki; Ishikawa, Hideki; Kitazono, Takanari; Matsumoto, Takayuki.

:: Clinical Gastroenterology and Hepatology, 巻 14, 番号 6, 01.06.2016, p. 809-815.e1.

研究成果: ジャーナルへの寄稿記事

Washio, Ema ; Esaki, Motohiro ; maehata, yuji ; Miyazaki, Masashi ; Kobayashi, Hiroyuki ; Ishikawa, Hideki ; Kitazono, Takanari ; Matsumoto, Takayuki. / Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury : A Randomized, Placebo-Controlled Trial. :: Clinical Gastroenterology and Hepatology. 2016 ; 巻 14, 番号 6. pp. 809-815.e1.
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title = "Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury: A Randomized, Placebo-Controlled Trial",
abstract = "Background and 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. Methods: 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. Results: 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. Conclusions: 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.",
author = "Ema Washio and Motohiro Esaki and yuji maehata and Masashi Miyazaki and Hiroyuki Kobayashi and Hideki Ishikawa and Takanari Kitazono and Takayuki Matsumoto",
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T1 - Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury

T2 - A Randomized, Placebo-Controlled Trial

AU - Washio, Ema

AU - Esaki, Motohiro

AU - maehata, yuji

AU - Miyazaki, Masashi

AU - Kobayashi, Hiroyuki

AU - Ishikawa, Hideki

AU - Kitazono, Takanari

AU - Matsumoto, Takayuki

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N2 - Background and 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background and 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. Methods: 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. Results: 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. Conclusions: 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.

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