Rifaximin Reduces the Number and Severity of Intestinal Lesions Associated With Use of Nonsteroidal Anti-Inflammatory Drugs in Humans

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 152; no. 5; pp. 980 - 982.e3
• Main Authors: Scarpignato, Carmelo, Dolak, Werner, Lanas, Angel, Matzneller, Peter, Renzulli, Cecilia, Grimaldi, Maria, Zeitlinger, Markus, Bjarnason, Ingvar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2017
• Subjects: Adult; Anti-Infective Agents - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Capsule Endoscopy; Controlled Trial; Delayed-Action Preparations; Diclofenac - adverse effects; Double-Blind Method; Female; Gastrointestinal Adverse Event; Gastrointestinal Microbiome; Humans; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Intestine, Small - microbiology; Intestine, Small - pathology; Logistic Models; Male; Microbiome; Omeprazole - therapeutic use; Prevention; Proton Pump Inhibitors - therapeutic use; Rifamycins - therapeutic use; Severity of Illness Index; Ulcer - chemically induced; Ulcer - pathology; Ulcer - prevention & control; Prevention; GI; Controlled Trial; CI; NSAID; mFA; VCE; Microbiome; Gastrointestinal Adverse Event; EIR
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2016.12.007

The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36.