Polaprezinc plus PPI noninferior to rebamipide plus PPI in ESD-induced ulcers

Treatment with polaprezinc plus proton pump inhibitor (PPI) is noninferior to rebamipide plus PPI in terms of ulcer healing rate at 4 weeks after endoscopic submucosal dissection (ESD), a Korea study has shown.

“ESD is widely used to treat gastric neoplasms,” the researchers said. “Although ESD shows higher en-bloc and curative resection rates than endoscopic mucosal resection, it causes larger and deeper artificial ulcers than endoscopic mucosal resection.” [Gastrointest Endosc Clin N Am 2014;24:213-233]

This study randomized 210 patients with ESD-induced ulcers to receive polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or rebamipide (300 mg/d) plus pantoprazole (40 mg/d). The researchers assessed the ulcer healing rate and condition of the ulcer at 4 weeks after dissection using the χ² or Fisher exact test and the Student t test.

At 4 weeks after dissection, the ulcer healing rates in the polaprezinc plus pantoprazole treatment arm were not inferior to those in the rebamipide plus pantoprazole treatment arm, both in the intention-to-treat analysis (90.3 percent and 91.4 percent, respectively; p=0.523) and per-protocol analysis (89.9 percent and 91.1 percent, respectively; p=0.531). [J Clin Gastroenterol 2021;55:233-238]

Additionally, short procedure time independently correlated with a high ulcer healing rate (odds ratio, 0.975, 95 percent confidence interval, 0.958–0.993; p=0.006).

“The long procedure time was an independent risk factor for a low ulcer healing rate, and this result might be associated with the use of more electrocautery during ESD,” the researchers said. “Electrocautery has been known to result in proper muscle damage. Therefore, electrocautery caused delayed ulcer healing after ESD.” [Dig Endosc 2015;27:747-753; Surg Endosc 2015;29:3666-3673]

Of note, patients in the rebamipide plus PPI group took 100-mg rebamipide three times a day, while those in the polaprezinc plus PPI group took 75-mg polaprezinc twice a day. Thus, one advantage of polaprezinc over rebamipide was its twice-a-day dosing.

“However, the cost of polaprezinc was 216 Korean won (KRW) and rebamipide 99 KRW, respectively,” the researchers said. “Therefore, the daily cost of polaprezinc was 432 KRW and rebamipide 297 KRW. The cost of polaprezinc was higher than that of rebamipide.”

Previous studies examining the effect of rebamipide on ulcer healing rate after ESD showed the superiority of rebamipide plus PPI to PPI monotherapy, but there were no reports about the effect of polaprezinc on the artificial ulcer healing rate after dissection relative to rebamipide.

“Polaprezinc, which is a complex chelating agent consisting of L-carnosine and zinc, is widely used as a mucoprotective agent to treat gastric ulcers,” the researchers said, noting its anti-inflammatory and antioxidant effects, and that its mechanisms are independent of prostaglandin. [Biochem Biophys Res Commun 2006;349:611-618; J Int Med Res 2018;46:2436-2444; J Physiol Pharmacol 2010;61:581-591]

Furthermore, the zinc L-carnosine heals hydrochloric acid-induced mucosal injury by inducing heat shock protein (HSP)-72 expression, the over-expression of which protects organs and cells including gastric mucosal cells against stress conditions. [J Gastroenterol Hepatol 2006;21:1669-1674; Thyroid 1996;6:475-483; Biochem J 1994;298:561-569]