Efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease: A protocol for meta-analysis and systematic review

Abstract

Objective :The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. Methods: PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. Discussion: The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment. Background: Gastroesophageal reflux disease (GERD) is a disease in which the contents of the stomach or duodenum flow back into the esophagus causing discomfort and/or complications, both physiologic and pathologic [1]. Typical symptoms are esophageal manifestations, with heartburn and reflux being the most characteristic, as well as chest pain and dysphagia [2, 3]. Extra-esophageal manifestations, such as laryngitis, chronic cough and asthma, and even hysteria such as foreign body sensation and blockage in the pharynx, can also be present [4]. In Asia, heartburn or reflux is diagnosed at least once a week, and then the endoscopic presentation of the esophagus is divided into three types: reflux esophagitis, non-erosive reflux disease and Barrett’s esophagitis [5]. The prevalence of GERD is increasing year by year, as shown by the recent publications [6, 7]. The pathogenesis of GERD is complex, and current treatment is based on the use of proton pump inhibitors to promote esophageal mucosal healing and gastrointestinal motility drugs to increase lower esophageal sphincter (LES) pressure [8]. Since the recurrence rate of the disease is 57%-90%, patients must take proton pump inhibitors and prokinetic drugs to relieve their symptoms for a long time [9]. Drugs such as histamine H2 receptor blockers and proton pump inhibitors (PPIs), which inhibit gastric acid secretion, are effective in the treatment of acid-related diseases and may improve patients’ quality of life [10]. However, there are still some limitations of the existing drug therapy. Some adverse effects of long-term proton pump inhibitors and prokinetic drugs have received attention in recent years: long-term use of proton pump inhibitors has led to the development of gastric adenocarcinoma, osteoporosis in the elderly, and bacterial overgrowth in the intestinal tract [11, 12], and the 5-hydroxytryptamine-4 agonist tegaserod has been discontinued because of the increase in serious cardiovascular system adverse effects. On the other hand, duodenal gastroesophageal reflux disease is a complex reflux disease with independent risk factors, and proton pump inhibitors are not effective in its treatment [13]. In recent years, a new potassium-competitiveacid blocker (P-CAB) has gained much attention because it can better overcome the disadvantages of PPIs. Unlike PPIs, P-CAB is a new type of highly efficient and selective gastric H+/K+-ATPase inhibitor that does not require activation in a strong acid environment to function. The greatest advantage of tegoprazan, a novel P-CAB, is its ability to bind to the K + binding site of H+/K+-ATPase in a competitive and reversible manner without acid activation and without any conversion, exhibiting faster gastric acid inhibition than PPIs and almost complete inhibition of gastric acid secretion [9, 14]. In addition, P-CAB-induced gastric acid inhibition is not affected by the ab initio synthesis of proton pumps in gastric lining cells, thus enabling faster maximal inhibition and longer duration of action, making P-CAB a novel, highly selective and efficient acid inhibitor [15, 16]. We present the first systematic review and meta-analysis protocol based on randomized controlled trials to investigate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease.