SummaryBackgroundVonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.AimTo verify the non‐inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long‐term safety and efficacy as maintenance therapy.MethodsIn this multicentre, randomised, double‐blind, parallel‐group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A–D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re‐randomised into a long‐term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks.ResultsOf the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long‐term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non‐inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long‐term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well‐tolerated.ConclusionsThe non‐inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well‐tolerated and effective during the long‐term maintenance study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to cause gastroduodenal mucosal lesions as an adverse effect. Recently, the serious problem of NSAID-induced small intestinal damage has become a topic of great interest to gastroenterologists, since capsule endoscopy and balloon enteroscopy are available for the detection of small intestinal lesions. Such lesions have been of great concern in clinical settings, and their treatment and prevention must be devised as soon as possible. The prevalence of NSAIDs-induced small intestinal injury is higher than had been expected. Recent studies show that more than 50% of patients taking NSAIDs have some mucosal damage in the small intestine. The gross appearance of NSAIDinduced enteropathy varies, appearing variously as diaphragm-like strictures, ulcers, erosions, and mucosal redness. To investigate NSAID-induced enteropathy, and to rule out other specific enteropathies, other useful methods (in addition to capsule endoscopy and balloon enteroscopy) include such modalities as radiological examination of the small intestine, the permeability test, scintigraphy or the fecal excretion test using 111 Indium-labeled white blood cells, and measurement of the fecal calprotectin concentration. Diaphragm-like strictures and bleeding from mucosal breaks may be treatable with interventional enteroscopy. Misoprostol, metronidazole, and sulfasalazine are frequently used to treat NSAID-induced enteropathy, but have undesirable effects in some cases. In the experimental model, we confirmed that several existing drugs for gastroduodenal ulcers prevented indomethacin-induced small intestinal injury. Such drugs may be useful for preventing the adverse effects of NSAIDs not only in the stomach but also in the small intestine. We hope to examine these drugs in future clinical studies.

SummaryBackgroundThe potassium‐competitive acid blocker vonoprazan (VPZ) has potent acid‐inhibitory effects and may offer clinical advantages over conventional therapy for acid‐related disorders.AimTo investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO).MethodsIn this multicentre, randomised, double‐blind, parallel‐group, dose‐ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A−D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4.ResultsA total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non‐inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups.ConclusionsVonoprazan was effective and non‐inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8‐week study, while there was a dose‐dependent increase in serum gastrin. Once‐daily VPZ 20 mg is the recommended clinical dose for treating EO.

BackgroundThere is a lack of consensus regarding the risk of postoperative hemorrhage in patients on antithrombotic therapy who undergo endoscopic submucosal dissection (ESD).We examined postoperative bleeding rates and risk factors for postoperative hemorrhage from post-ESD gastric ulcers in patients on antithrombotic therapy.MethodsThe subjects of this study were 833 patients who underwent ESD of gastric tumors. Of these, 743 were not on antithrombotic therapy and 90 were on some form of antithrombotic therapy (46 on low-dose aspirin (LDA) only, 23 on LDA + thienopyridine, and 21 on LDA + warfarin). All patients commenced proton pump inhibitor (PPI) therapy immediately postoperatively. Antiplatelet agents were discontinued for 7 days preoperatively and postoperative Day 1, and anticoagulants for 5 days preoperatively and postoperative Day 1.ResultsThe postoperative bleeding rate in the antithrombotic group was 23.3%, significantly higher than the 2.0% observed in the non-antithrombotic group. Significant differences were seen in patients in the antithrombotic group with and without postoperative bleeding according to ESD duration (p = 0.041), PPI + mucosal protective agent combination therapy (p = 0.039), and LDA + warfarin combination therapy (p < 0.001). Multivariate analysis of these factors yielded odds ratios of 1.04 for ESD duration, 14.83 for LDA + warfarin combination therapy, and 0.27 for PPI + mucosal protective agent combination therapy.ConclusionsThe risk of postoperative hemorrhage following gastric ESD was higher in patients with antithrombotic therapy than in those without that therapy. Among these patients, LDA + warfarin combination therapy and longer ESD duration were significant risk factors for postoperative bleeding. On the contrary, a mucosal protective agent to PPI therapy, lowering the odds ratio for postoperative bleeding, which suggests that the addition of a mucosal protective agent might be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy.

AIMTo compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE).METHODSA total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results.RESULTSRates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSIONOur findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.