Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity
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Background/Aims: The use of proton pump inhibitors ormisoprostol is known to prevent the gastrointestinal complicationsof nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation ofprostaglandins and to eliminate free oxygen radicals, thusenhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role inpreventing NSAID-induced gastropathy. The aim of this studywas to determine the effectiveness of rebamipide comparedto misoprostol in preventing NSAID-induced gastrointestinalcomplications in patients requiring continuous NSAID treatment. Methods: We studied 479 patients who required continuousNSAID treatment. The patients were randomly assignedto groups that received 100 mg of rebamipide threetimes per day or 200 μg of misoprostol three times per dayfor 12 weeks. The primary endpoint of the analysis was theoccurrence rate of gastric ulcers, as determined by endoscopyafter 12 weeks of therapy. Results: Of the 479 patients inthe study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from themisoprostol group and 25 patients (10.3%) withdrew fromthe rebamipide group. There was a significant difference inwithdrawal rate between the two groups (p=0.0103). The perprotocol analysis set was not valid because of the dropoutrate of the misoprostol group; thus, the intention to treat (ITT)analysis set is the main set for the efficacy analysis in thisstudy. After 12 weeks, the occurrence rate of gastric ulcerswas similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition,the therapeutic failure rate was similar in the rebamipideand misoprostol groups (13.6% vs 13.1%, p=0.8580). Thetotal severity score of the gastrointestinal symptoms wassignificantly lower in the rebamipide group than in the misoprostolgroup (p=0.0002). The amount of antacid used wassignificantly lower in the rebamipide group than in the misoprostolgroup (p=0.0258). Conclusions: Rebamipide canprevent gastric ulcers when used with NSAIDs and can decreasethe gastrointestinal symptoms associated with NSAIDadministration. When the possibility of poor compliance andthe potential adverse effects of misoprostol are considered,rebamipide appears to be a clinically effective and safe alternative.
Abstract
Background/Aims: The use of proton pump inhibitors ormisoprostol is known to prevent the gastrointestinal complicationsof nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation ofprostaglandins and to eliminate free oxygen radicals, thusenhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role inpreventing NSAID-induced gastropathy. The aim of this studywas to determine the effectiveness of rebamipide comparedto misoprostol in preventing NSAID-induced gastrointestinalcomplications in patients requiring continuous NSAID treatment. Methods: We studied 479 patients who required continuousNSAID treatment. The patients were randomly assignedto groups that received 100 mg of rebamipide threetimes per day or 200 μg of misoprostol three times per dayfor 12 weeks. The primary endpoint of the analysis was theoccurrence rate of gastric ulcers, as determined by endoscopyafter 12 weeks of therapy. Results: Of the 479 patients inthe study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from themisoprostol group and 25 patients (10.3%) withdrew fromthe rebamipide group. There was a significant difference inwithdrawal rate between the two groups (p=0.0103). The perprotocol analysis set was not valid because of the dropoutrate of the misoprostol group; thus, the intention to treat (ITT)analysis set is the main set for the efficacy analysis in thisstudy. After 12 weeks, the occurrence rate of gastric ulcerswas similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition,the therapeutic failure rate was similar in the rebamipideand misoprostol groups (13.6% vs 13.1%, p=0.8580). Thetotal severity score of the gastrointestinal symptoms wassignificantly lower in the rebamipide group than in the misoprostolgroup (p=0.0002). The amount of antacid used wassignificantly lower in the rebamipide group than in the misoprostolgroup (p=0.0258). Conclusions: Rebamipide canprevent gastric ulcers when used with NSAIDs and can decreasethe gastrointestinal symptoms associated with NSAIDadministration. When the possibility of poor compliance andthe potential adverse effects of misoprostol are considered,rebamipide appears to be a clinically effective and safe alternative.
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