A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated gastroduodenal injury in patients undergoing chronic NSAID treatment

Abstract

Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). A total of 236 patients received DA-9601 and 242 received misoprostol. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was −14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (−0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.

Anti-inflammatory effects of DA-9601, an extract of Artemisia asiatica, on aceclofenac-induced acute enteritis

“…These adverse reactions have emerged as a factor that limits the prescription for patients, such as those suffering from rheumatoid arthritis, who require long-term administration of ACF [9]. DA-9601 is an ethanol extract of Artemisia asiatica and is currently used as a clinical medicine for the treatment of gastritis [10]. Interestingly, it has been reported to have anti-oxidative and antiinflammatory effects on experimentally induced gastrointestinal, hepatic, and pancreatic lesions [11,12].…”

Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

“…The three strains have different effects on TLRs signaling and differently stimulate cytokine production in vitro in immune cells ( 3 , 10 , 11 ). Healthy volunteers received the NSAID indomethacin, which induces mild and reversible damage to the gastrointestinal lining ( 21 – 24 ). Study participants subsequently consumed one of the three L. plantarum strains or placebo for a week.…”

Antiulcerogenic benefits of herbal ingredients in ethanol-induced animal models

“…In addition, a meta-analysis showed that H. pylori eradication was not as effective as proton pump inhibitors for preventing NSAIDs-associated ulcers (Vergara et al, 2005). Even though proton pump inhibitors, H2 blockers and prostaglandin E1 analog display some preventive benefit for gastric ulcer (Cullen et al, 1998;Graham et al, 2002;Hawkey et al, 1998; Lee et al, 2014;Medlock et al, 2013;Raskin et al, 1995 andScheiman et al, 2006), an over 77% adverse effect rate could prevent these drugs from clinical usage (Lee et al, 2014;Raskin et al, 1996). In contrast, studies have demonstrated that herbal medicines can effectively prevent the formation of gastric ulcer with fewer side effects in various animal models, suggesting the potential utilization of herbal medicines for preventing gastric and/or duodenal ulcers.…”