Sa1735 Prophylactic Effect of Gastromucoprotective Drugs on NSAIDs-Induced Esophageal, Gastric, Duodenal, and Small Intestinal Mucosal Injury in Healthy Subjects: A Prospective Randomized Study

Abstract

Sa1735 Prophylactic Effect of Gastromucoprotective Drugs on NSAIDsInduced Esophageal, Gastric, Duodenal, and Small Intestinal Mucosal Injury in Healthy Subjects: A Prospective Randomized Study Eiji Umegaki*, Yuichi Kojima, Yukiko Yoda, Takanori Kuramoto, Sadaharu Nouda, Toshihisa Takeuchi, Kumi Ishida, Takuya Inoue, Satoshi Tokioka, Kazuhide Higuchi 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan Introduction: A variety of factors are involved in the formation of lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs) in the small intestine, considered unaffected by acid, including intestinal flora, bile, and mucus, and as yet there are no established preventive or therapeutic measures. Gastromucoprotective agent such as geranylgeranylacetone (GGA), irsogladine (IG), and rebamipide (REB), is used in the treatment of gastritis and gastric ulcers, and prevented NSAID-induced small intestinal lesions in rats (Gastroenterology 2010;138:A-528). Recently there was the report that proton pump inhibitors exacerbate NSAID-induced small intestinal injury by iducing dysbiosis (Gastroenterology 2011;141:1314). In this study, we investigated whether gastromucoprotective agent monotherapy can protect against NSAIDinduced esophageal, gastric, duodenal, and small intestinal mucosal injury. Subjects and Methods: We randomly allocated healthy volunteers(each group: n 15), aged 20 years, to take (1) diclofenac 75mg plus famotidine 20mg daily or diclofenac 75mg plus GGA 150mg daily, (2) diclofenac 75mg plus omeprazole 10mg or diclofenac 75mg plus IG 4mg, (3) aspirin 100mg plus omeprazole 10mg, aspirin 100mg plus REB 300mg or aspirin 100mg plus REB 900mg. All subjects underwent upper gastrointestinal endoscopy and video capsule endoscopy(VCE) before and 2 weeks after the treatment period, and were evaluated for gastric and small intestinal lesions. Upper gastrointestinal mucosal injury was evaluated using the Modified Lanza Score(MLS), and small intestinal changes were scored for the number of 6 lesion types of: erythema, haemorrhage, erosions, ulcers, edema, and strictures. In addition, we measured fecal calprotectin levels, as a marker of digestive tract mucosal permeability. Results: 1)No significant differences were seen between gastromucoprotective agent groups and acid suppressive agent groups in the background of volunteers, and in the mean increase in esophageal, gastric and duodenal mucosal lesions. 2)When examining the total number of small intestinal mucosal injury, lesion development was suggested after administration in acid suppressive agent groups. However, there was no development in gastromucoprotective agent groups. 3)GGA/IG/REB significantly inhibited an increase in the fecal calprotectin level in comparison with acid suppressive agent in patients with NSAIDs-related digestive tract mucosal injury. Conclusions: A similar protective effect against NSAID-induced acute esophageal, gastric and duodenal mucosal injury was seen for gastromucoprotective agent and acid suppressive agent. The protective effect in the small intestine was clearly superior for gastromucoprotective agent, however, indicating that GGA/IG/REB monotherapy can protect against NSAID-induced acute mucosal injury to the esophagus, stomach, duodenum and small intestine.