Submit manuscript...
eISSN: 2373-6372

Gastroenterology & Hepatology: Open Access

Research Article Volume 13 Issue 6

Vonoprazan: A systematic review of an alternative to proton pump inhibitors

Gabriel AV Silva, Julia S Figueiredo, Ricardo JB Gonçalves, Matheus GPO Barbosa, Ethel Z Chehter

Department of Gastroenterology, Centro Universitário Faculdade de Medicina do ABC, Brazil

Correspondence: Ethel Z. Chehter, Centro Universitário Faculdade de Medicina do ABC, Av. Lauro Gomes, 2000, Santo André-SP, Brazil, Tel +55 11 99962-9456

Received: November 12, 2022 | Published: November 25, 2022

Citation: Silva GAV, Figueiredo JS, Gonçalves RJB, et al.Vonoprazan: A systematic review of an alternative to proton pump inhibitors. Gastroenterol Hepatol Open Access. 2022;13(6):221-231. DOI: 10.15406/ghoa.2022.13.00527

Download PDF

Abstract

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that works through a reversible potassium-specific competitive mechanism to inhibit active proton pumps directly. In contrast to standard proton pump inhibitors, vonoprazan does not require acid activation or any time constraints for its administration. As a result of its rapid onset and prolonged action, vonoprazan is a suitable option for PPI. In this study, we compare the efficacy of vonoprazan and PPIs in treating Gastroesophageal Reflux Disease (GERD), H. pylori, and post-endoscopic submucosal dissection (ESD) bleeding and ulcers. A PRISMA-guided systematic review was conducted on Pubmed. It included English or Portuguese articles published in the last five years describing adult patients treated with vonoprazan and/or PPI for GERD, H. pylori, or post-endoscopic dissection of the gastroesophageal submucosa bleeding and ulcers. There were six articles on GERD. Half suggested vonoprazan was superior to PPIs, while the other half considered it non-inferior or of comparable efficacy. There were 19 articles on H. pylori eradication, and vonoprazan outperformed PPI in 68,42% (13/19) of them. Vonoprazan was more effective than PPIs in 8 of the 13 studies chosen for post-ESD and ulcer prevention. As a result, in most studies, vonoprazan is either superior or not inferior to PPIs. However, the racial bias of the results is a significant limitation, as many of these studies were conducted in the Japanese population. More research on greater racial diversity is required. Nonetheless, in the current scenario, vonoprazan is a potential alternative pharmacological treatment for post-ESD bleeding and ulcers, GERD, and H. pylori.

Keywords: acid suppression agents, proton pump inhibitor, potassium-competitive acid blocker, vonoprazan

Abbreviations

P-CAB, potassium-competitive acid blockers; PPI, proton pump inhibitors; GERD, Gastroesophageal Reflux Disease; ESD, endoscopic submucosal dissection; OR, odds ratio; CI, confidence interval; UGET, upper digestive endoscopic treatment; RR, relative risk

Introduction

Since 1990, proton pump inhibitors (PPIs) have been the standard treatment for acid-related diseases such as gastroesophageal reflux disease (GERD), as well as for the prevention of bleeding and ulceration after endoscopic gastroesophageal submucosa dissection (ESD) and the eradication of Helicobacter pylori. GERD is one of the most common gastroenterological diseases in the United States and Europe, affecting 20-30% of the global population. Serious complications such as stricture, ulceration, or Barrett's esophagus may develop if treatment is ineffective.1 Endoscopic gastroesophageal submucosal dissection (ESD) has become a standard treatment for early gastric cancer that has not spread to lymph nodes. However, bleeding from the resection site remains a significant complication, with a 3-5% incidence.2 H. pylori is one of the most common bacterial pathogens in the world, accounting for approximately 50% of the global population, and its treatment is based on PPIs and antibiotics.2

Despite PPIs being essential in treating these conditions, critical therapeutic limitations exist. In GERD, approximately two-thirds of symptomatic patients do not have adequate control of their reflux symptoms after the first dose of PPI, and approximately half of them continue to have symptoms even after a few days of starting therapy.3 Additionally, the standard dose of PPIs cannot always induce acid suppression because of their pharmacological limitations, such as their need to be activated by gastric acid, which delays the onset of its pharmacological effects.4 PPIs are the preferred therapy for ulcers and post-ESD bleeding, but there is no standard treatment plan, especially concerning the length of time and method of administration.5 The success of combining PPIs with antibiotics in cases of H. pylori has been hampered by rising antimicrobial resistance.2 Even though PPIs are already a well-established and effective drug therapy for treating these diseases, there is still room for new drugs that may supplement PPI-based treatment.

In this scenario, other acid secretion-suppressing drugs were developed to treat the same conditions as PPIs6 Vonoprazan, a potassium-competitive acid blocker (P-CAB)7 developed by Takeda Pharmaceutical Company, can directly inhibit H+/K+-ATPase-mediated gastric acid secretion by reversibly competing with potassium ions, bypassing the need for acid activation.8 Furthermore, vonoprazan has a higher positive charge than other P-CABs, allowing it to accumulate in the canalicular space of parietal gastric cells, enhancing and prolonging its anti-secretory effects. vonoprazan has a rapid release due to its acid resistance, with studies from Japan and the United Kingdom indicating that the maximum plasma concentration is reached 1.5-2.0hours after oral intake on an empty stomach.9 Excretion occurs after nine hours on average.10 The most common side effects of vonoprazan are similar to those of PPIs and include diarrhea, nasopharyngitis, dyspepsia, headache, and abdominal pain.11

P-CABs have different mechanisms of action and pharmacokinetics that can overcome the limitations of PPIs. Therefore, this review aims to compare the therapeutic efficacy of vonoprazan and PPIs in treating GERD, H. pylori, ulcers, and post-ESD bleeding.

Methods

The present review followed PRISMA PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines. An article search was conducted in Pubmed starting on April 27th, 2022. The following search terms were used: "vonoprazan + PPI," "vonoprazan + GERD," "vonoprazan + UGIB," "vonoprazan + bleeding," "vonoprazan + H. pylori eradication," and "PCAB + PPI."In total, 316 articles were found.

Inclusion criteria were studies written in English or Portuguese that compared the efficacy of the PPI versus vonoprazan-based therapeutic regimen in GERD, H. Pylori eradication, and prevention of bleeding and ulceration after ESD in adult patients (>18years old)Articles that did not compare vonoprazan to PPI-based treatment were excluded. According to the PRISMA diagram (Figure 1), 175 studies were excluded after reading the titles and abstracts and 63 after reading the full article, leaving 38 studies to be analyzed in this systematic review. Data extraction was carried out by four independent reviewers and checked by a senior reviewer.

Figure 1 PRISMA diagram.

Results

The articles were divided into three categories. The first category was GERD treatment. Six articles were selected, out of which three were systematic reviews and meta-analyses: one was a randomized control study, one was a comparative study, and one was a prospective cohort study. Moreover, four of these studies were Japanese, one was Chinese-Japanese, and one was exclusively Chinese.

The second category was H. Pylori eradication. There were 19 studies, ten meta-analyses, one systematic review, three randomized controlled trials, one observational study, two randomized controlled trials, and two retrospective studies. Eleven of these studies were from Japan, five from China, one from South Korea, one from Thailand, one from Indonesia, and one from multiple countries, including the USA, Israel, Italy, France, and Spain.

Finally, the third category was the prevention of post-ESD bleeding and ulcers, which included 13 articles: 2 retrospective cohort studies, six meta-analyses, four prospective studies, and one case-control randomized study. Among these studies, nine were Japanese, one was from the USA and Thailand, one was from South Korea, and one was from China.

Prevention of post-ESD bleeding and ulcers(Table 1)

Study type

Country

Number of articles revised

Number of patients

 

Goal

Intervention

Results

Is vonoprazan better than PPI?

Ref

Systematic review and Meta-analysis

South Korea

12

1265

To compare vonoprazan and PPIs in treating post-ESD ulcers and preventing bleeding

Vonoprazan (20mg/day) or PPIs like lansoprazole, rabeprazole, omeprazole or esomeprazole

Scar tissue formation post-endoscopy was higher after four weeks of vonoprazan.  However, after eight weeks, PIIs had better ulcer healing

Yes, after four weeks of treatment

47

Systematic review and Meta-analysis

China

7

548

To compare vonoprazan's and PPI's efficiency and safety doses in treating

Vonoprazan (20mg/day) or PPIs like lansoprazole, rabeprazole or omeprazole for 4 to 8 weeks post-ESD

No difference

Similar

19

Systematic review and Meta-analysis

Several

6

461

To compare vonoprazan's and PPI's efficacy in scar formation in post-ESD ulcers

Vonoprazan or PPI for 4 to 8weeks post-ESD

Greater scar formation and less late bleeding in post-ESD ulcers following vonoprazan therapy

Yes

48

Prospective observational study

Japan

-

621

To compare vonoprazan's and PPI's efficacy in preventing post-ESD bleeding

Vonoprazan (20mg/day) or esomeprazole  (20mg/day), rabeprazole (40mg/day), or lansoprazole (30mg/day)

No difference in ulcer scaring.  Vonoprazan was better in reducing bleeding post-ESD

Yes

26

Retrospective cohort

Japan

-

1715

To compare the effect of vonoprazan and PPIs in post-ESD bleeding

Omeprazole (20mg/day) for 2days, then vonoprazan (20 mg/day) or lansoprazole (dose?) for 12days

Vonoprazan was more effective in reducing ulcers and forming granulation tissue

Yes

18

Retrospective cohort study

Japan

-

115

To compare the effect of vonoprazan and lansoprazole in ulcer scaring formation related to ESD in the two first weeks post-intervention

Omeprazole (20mg/day) in the first two days, then vonoprazan (20mg/day) or lansoprazole (30mg/day) for 12days

Vonoprazan reduced ulcer size and granulation tissue more significantly than lansoprazole.  Bleeding post-surgery was not observed in any of the groups

Yes

49

Retrospective cohort study

Japan

-                       

124,422

To compare the effect of vonoprazan and PPIs in preventing post-ESD bleeding

Vonoprazan dose was categorized into standard/high

dose (>20mg/day) and low dose (<20mg/day).

Regarding PPIs, the standard daily dose in Japan is 30, 10,

20 and 20mg in lansoprazole, rabeprazole, esomeprazole,

and omeprazole, respectively. Hence, the PPI dose in this study was categorized into

two groups: standard/high-dose PPI and low dose, which

included the dose under the standard dose of each PPI.

 

Vonoprazan was associated with a lower risk of late bleeding

Yes

11

Meta-analysis

Japan

13

1214

To discuss vonoprazan and PPIs' efficacy in preventing ESD-induced bleeding

10mg vonoprazan, 20mg vonoprazan, and 20mg vonoprazan combined with 300mg rebamipide. Control arm (PPI) studies included 30mg lansoprazole, 20mg lansoprazole plus 300mg rebamipide, 20mg esomeprazole, 30mg lansoprazole, 20mg omeprazole, 10mg rabeprazole, and 20mg rabeprazole

No difference

Similar

50

Randomized clinical studies

Japan

-

168

Evaluate how vonoprazan helps in ulcer healing post-ESD

20mg/day of vonoprazan and 3 mg/day of lansoprazole for 8weeks

No difference

Similar

29

Meta-analysis

China

14

1328

Evaluate the efficacy and safety of vonoprazan in healing ulcers and preventing post-ESD bleeding

 

Vonoprazan reduced the risk of bleeding post-ESD

Yes

51

Prospective randomized study

Japan

-

80

To compare the effect of vonoprazan and PPIs in preventing post-ESD bleeding

Vonoprazan (20mg/day) or esomeprazole (20mg/day) for 8weeks

No significant difference between vonoprazan and PPIs

Similar

52

Prospective randomized study

Japan

-

33

To compare the effect of vonoprazan and PPIs in preventing post-ESD bleeding

Vonoprazan (20mg/day) or rabeprazole (10mg/day) for four weeks, starting one day before ESD.

Vonoprazan was better than PPIs in preventing late bleeding

Yes

53

Table 1 Studies on the use of vonoprazan or proton pump inhibitors to treat post-ESD ulcer and prevent late bleeding
Abbreviations: PPI, proton pump inhibitors; ESD, endoscopic submucosal dissection.

In the study by Abe et al.11 124,422 upper digestive endoscopic treatment (UGET) patients were analyzed between 2014 and 2019, with 34,822 and 89,600 prescribed vonoprazan and PPIs, respectively. The risk of late bleeding was lower in the vonoprazan group than in the PPI group. vonoprazan was significantly beneficial in endoscopic esophageal submucosal dissection (E-ESD) (OR, 0.71; 95% CI, 0.54-0.94) and endoscopic gastroduodenal submucosal dissection (GD-ESD) subgroup analyses of seven UGET procedures (OR, 0.70; 95% CI, 0.65-0.75).

PPIs were administered two days before the procedure in Shiratori et al.18 carried out in nine hospitals with a total of 1715 patients. After ESD, patients were randomly assigned to treatment with vonoprazan or PPIs. The Post-ESD bleeding rates were significantly lower in the vonoprazan group than in the PPI group (overall, 11.9% vs. 17.2%, P=0.008; bleeding between days 2 and 30, 7.8% vs. 11.8%, P =0.015). In addition, the vonoprazan group had a lower readmission rate for post-ESD bleeding (2.4% vs. 4.1%, P=0.081).

Two studies compared the effects of vonoprazan and PPIs in treating ESD-induced artificial ulcers and preventing late bleeding. Following ESD, patients were given vonoprazan 20mg or PPIs (Lansoprazole, Omeprazole, Rabeprazole) for four or eight weeks. In He et al.19 the success rates of vonoprazan-based and PPI-based therapy were equivalent. The combined relative risk (RR) for vonoprazan compared to PPI treatment for ESD was 0.64 (95% CI, 0.33-1.22) for the four-week study group and 0.98 (95% CI, 0.84-1.15) for the eight-week study group. The RR for adverse events was 0.65 (95% CI, 0.31-1.38) (p>0.05). However, in Kang et al.20 the vonoprazan group recovered significantly faster than the PPI group four weeks after the endoscopy. In the same study, the PPI group had a significantly higher healing rate than the vonoprazan group at eight weeks post-endoscopy. All patients in Horikawa et al.20 received an intravenous infusion of omeprazole during the first two days. Following the ESD procedure, patients were randomly assigned to either 20mg vonoprazan (P-CAB group) or 30mg lansoprazole (PPI group) treatment. All treatments were given orally for 12days. When comparing the PPI and P-CAB regimens, ulcers were smaller (median [range], 80.6% [67.6%–94.5%] vs. 62.7% [33.4%–85.2%]; p<0.0001) and granulation was faster (median [range], 84.1% [67.7%–95.3%] vs. 61.9% [12.1%–90.1%]; p<0.0001) in the P-CAB group. Moreover, postoperative bleeding was not observed in any of the groups.

Jaruvongvanich et al.21 analyzed six studies (three cohort studies and three randomized studies) involving 461 patients (215 in the vonoprazan group and 246 in the PPI group) that compared vonoprazan-based and PPI-based treatment for four or eight weeks after mucosectomy. Upper digestive tract endoscopy was used to simultaneously measure and report post-ESD bleeding and complete ulcer healing rates in both groups. Patients who received vonoprazan had a significantly higher chance of having their ESD ulcers healed four-eight weeks after the procedure, with a combined odds ratio (OR) of 2.27 (95% CI: 1.38-3.73) than those who received PPIs. In addition, the four-week and eight-week subgroups had significantly higher rates of fully healed ulcers, with pooled ORs of 2.21 (95% CI: 1.19-4.08; I2=0%) and 2.40 (95% CI: 1.04-5.55; I2=0%), respectively. The risk of developing late post-ESD bleeding was lower among those who received vonoprazan, with a pooled OR of 0.79, although the result did not reach statistical significance (95% CI: 0.18–3.49).

In their meta-analysis, Martin et al.22 included only randomized controlled trials and observational monotherapy studies with vonoprazan or those that combined vonoprazan with a mucosa-protective agent. The overall OR for late bleeding was 0.66 (P=0.26) with a (95% CI: 0.32-1.35). After excluding drug combination studies, the overall ORs for vonoprazan and PPIs to promote ulcer healing and prevent late bleeding were 1.44 and 0.76, respectively. Vonoprazan was thus comparable to PPIs for preventing delayed bleeding after ESD, as the differences between the two drug classes were not statistically significant.

In their meta-analysis, Liu et al.23 included fourteen articles with 1,328 patients. Vonoprazan outperformed PPIs regarding ulcer reduction rate (mean difference 0.56, 95% CI: 0.18-0.93). Additionally, with vonoprazan, there was more scar formation (OR 1.58, 95 % CI 1.00-2.47) and lower bleeding risk post-ESD (OR 0.69) compared to PPIs, although there was no statistically significant difference.

In Yang et al.24 five studies evaluated the effectiveness of vonoprazan in post-ESD ulcers. Two of the five studies yielded favorable results for vonoprazan, two yielded favorable results for PPIs, and one yielded no difference in results between vonoprazan and PPIs. As a result, it is unclear whether vonoprazan is superior to PPIs in healing ulcers after ESD. More research into PPI-based unified administration is needed.

Hirai et al.25 performed a prospective randomized controlled trial with 149 patients to compare the effects of vonoprazan and lansoprazole in treating ESD-induced ulcers and preventing bleeding. Patients received 40 mg of intravenous omeprazole for the first two days post-ESD and 20 mg of vonoprazan or 30mg of lansoprazole daily for eight weeks. There was no significant difference in ulcer resolution or prevention of late bleeding between the two groups.

Ishida et al.26 treated post-endoscopy gastric cancer patients (≥20years old) with PPI (n=398) or vonoprazan (n=223) patients. One day before the endoscopy, the PPI group received oral esomeprazole (20mg/day), rabeprazole (40 mg/day), or lansoprazole (30 mg/day), followed by intravenous omeprazole (40mg/day), lansoprazole (60mg/day), and rebamipide (300mg/day). Succeeding that, oral medication was continued. PPI treatment was continued for at least eight weeks after endoscopy, and esophagogastroduodenoscopy was performed eight weeks later. In the other group, oral vonoprazan (20mg/day) was started one day before surgery and continued for six weeks, followed by esophagogastroduodenoscopy. Ulcers were scarred in 68.3% of patients after six weeks of vonoprazan and 74.6% after eight weeks of PPI.

Tsuchiya et al.27 looked at 92 gastric cancer patients who had ESD and were given vonoprazan (20mg/day) or esomeprazole (20mg/day) for eight weeks. The ulcer healing rate was better for vonoprazan than esomeprazole (94.9% [37/39] vs. 78.0% [32/41], respectively; P=0.049). However, in a multivariate analysis, only vonoprazan was correlated with ulcer healing (OR 6.33; 95% CI: 1.21-33.20; P=0.029).

Komori et al.28 looked at 40 gastric cancer patients who had ESD and were given vonoprazan (20mg/day) or rabeprazole (10mg/day), starting one day before ESD and continuing for four weeks. Ulcer size was measured before ESD and after four weeks of treatment. The mean ulcer reduction rate was lower in the vonoprazan (93.3%) than in the rabeprazole group (96.6%). In addition, post-ESD bleeding (n=2) and drug-induced liver injury (n=1) were observed in the rabeprazole group.

Kawai et al.29 randomly assigned 168 gastric cancer patients to receive intravenous lansoprazole (30mg) twice daily before ESD and vonoprazan (20mg/day) or lansoprazole (30mg/day) post-ESD. Esophagogastroduodenoscopy was also performed between four and eight weeks after ESD. There was no significant difference in ulcer healing between the two groups. Additionally, there was no postoperative bleeding, and only one patient presented late perforation two days after ESD.

Vonoprazan was more effective in preventing bleeding and ulcer reduction in eight (8/13-61.5%) of the 13 studies that compared the effect of vonoprazan and PPIs on bleeding and ulcer prevention after ESD. Another three studies (3/13-23%) found that vonoprazan and PPIs were equally effective in preventing ulcers and bleeding. However, in one of these studies, when patients were analyzed four or eight weeks after ESD, vonoprazan performed better in the first four weeks, while PPIs performed better at eight weeks. As a result, vonoprazan has an excellent therapeutic effect in preventing ESD-induced bleeding and artificial ulcers, with results comparable to or better than PPI therapy. However, most of these studies were conducted in Asian countries. Therefore, further research in other countries must determine vonoprazan's global effectiveness.

Gastroesophageal reflux disease treatment (Table 2)

Study type

Country

Number of articles revised

Number of patients

 

Goal

Intervention

Results for GERD symptom resolution

Is vonoprazan better than PPI?

Ref

Meta-analysis and systematic review

China and Japan

6

-

To compare PPI and vonoprazan efficiency in treating DRGE

Vonoprazan (20mg/day) or esomeprazole ou lansoprazole (15 to 30 mg/day)

Vonoprazan was superior in treating erosive esophagitis than PPIs.

Similar

12

Randomized clinical trial

Japan

-

60

To compare esomeprazole and vonoprazan in reducing GERD symptoms

Vonoprazan (20 mg/day) or esomeprazole (20 mg/day)

No difference

Similar

13

Comparative studies

Japan

-

12,069

To compare the adverse effects of vonoprazan and PPIs

 

No difference

Similar

14

Systematic review with network  meta-analysis

Japan

23

-

To compare the efficacy of vonoprazan and PPIs

Vonoprazan (10 mg/day), esomeprazole (10 mg/day) and omeprazole (10 mg/day)

Vonoprazan was better than esomeprazole and omeprazole in reducing GERD symptoms; however, it was not better than other PPIs

Yes

15

Prospective cohort

Japan

-

124

To analyze the use of vonoprazan in GERD patients not responding to PPIs

Omeprazole (20 mg/day), lansoprazole (30 mg/day), rabeprazole (10 or 20 mg/day) or esomeprazole (20 mg/day) and then vonoprazan (20 mg/day) was given for 8 weeks.

Vonoprazan reduced GAET (41.1%; p = 0.01), suppressed esophageal acid exposure in 46% (p=0.005), and improved reflux (p<0.01) and esophagitis (p=0.01) symptoms.

Yes

16

Meta-analysis

China

-

18

To compare the effect of vonoprazan and PPIs in treating GERD and H. pylori

 

Vonoprazan improved symptoms in patients resistant to PPIs and helped post-ESD ulcer healing. It was also a better drug for first-line H. pylori therapy.

Yes

17

Table 2 Studies on the treatment of gastroesophageal reflux disease with vonoprazan or proton pump inhibitors
Abbreviations: PPI, proton pump inhibitors; GERD, gastroesophageal reflux disease; ESD, endoscopic submucosal dissection.

Cheng et al.44 and Miwa et al.45 compared vonoprazan and PPIs as first-line and maintenance GERD treatments, respectively. Vonoprazan (10 mg/day) showed a better response than esomeprazole (10mg/day) or omeprazole (10 mg/day), but it was not better than other PPIs prescribed in Japan. On the other hand, Yang et al.46 demonstrated that vonoprazan was as effective as PPIs in treating erosive esophagitis and was an excellent option for GERD patients who no longer responded to PPIs.

Sakurai et al.13 administered vonoprazan or esomeprazole once daily for four weeks to two groups of 30 GERD patients. Symptoms' improvement was assessed through a questionnaire to track the clinical improvement. There was no significant difference in GERD symptom relief between vonoprazan and esomeprazole.

Kambara et al.14 compared patient-reported adverse effects of vonoprazan and PPIs from 2004-2017 using the Japanese database "Adverse Drug Event Repo." The adverse effects of both treatments were similar.

Akiyama et al.16 analyzed chronic GERD patients that did not respond to PPI therapy. Out of 124 patients undergoing multichannel intraluminal impedance-pH monitoring, 13 patients were monitored during PPI therapy and after introducing vonoprazan therapy. Median gastric acid exposure times associated with vonoprazan treatment (23.8%) were lower than for PPI treatment (41.1%; p=0.01), including daytime and nighttime measurements. In addition, vonoprazan resulted in lower esophageal acid exposure time (4.5%) than PPIs (10.6%) during the 24-hour monitoring period (p=0.055). Additionally, vonoprazan reduced gastric acid secretion in 46% of esophageal acid-exposed patients (p=0.005), improved reflux symptoms (p=0.01), and decreased erosive esophagitis (p=0.01).

GERD is a highly prevalent disease worldwide, mainly due to changes in lifestyle, diet, and obesity. Although GERD has been classically treated with PPIs, many patients have been unresponsive. Therefore, looking for new treatment options is critical to close this gap and improving quality of life. Here we examined six studies comparing vonoprazan to PPIs in the first-line and maintenance treatment of GERD patients. In three of these studies (50%), vonoprazan was considered superior to PPIs, and in the other three (50%), vonoprazan was similar to PPIs in treating GERD. Vonoprazan appears to be a promising first-line and maintenance GERD treatment. However, the small number of studies and lack of research outside of the Japanese population continue to be barriers to accepting this new drug as a replacement for PPIs.

H. Pylori eradication (Table 3)

Study type

Country

Number of articles revised

Number of patients

 

Goal

Intervention

Results for H. pylori eradication

Is vonoprazan better than PPI?

Ref

Meta-analysis

Spain, Israel, Italy, USA, France

68

22,975

 

To compare first-line treatments to eradicate H. pylori

Comparison between vono-triple therapy, non bismuth quadruple therapy, r-hybrid therapy, levo-therapy, sequential therapy, amox-dual therapy and bismuth quadruple therapy

90% remission in vonoprazan-based therapy

Yes

30

Systematic review with meta-analysis

South Korea

10

10,644

 

To compare vonoprazan and PPI

Vonoprazan (20mg/day) for 7 days or lansoprazole (30mg/day), rabeprazole (10mg/day),  esomeprazole (20mg/day) for 7days

87.9% remission in vonoprazan-based treatment; 72.8% remission in PPI-based treatment

Yes

31

Meta-analysis

China

8

2012

To analyze vonoprazan's efficacy and safety concerning other drugs

Vonoprazan (20mg/day) or PPI in association with amoxicillin (750mg/day) and clarithromycin 200mg or 400mg/day)

Equal or superior remission with vonoprazan-based treatment

Yes*

32

Systematic review

Japan

12

-

To compare sitafloxacin-based third-line therapies with others

Sitafloxacin, amoxicillin, and vonoprazan or PPI

Superior remission of vonoprazan-based treatments

Yes

33

Randomized clinical trial

Thailand

-

122

To compare seven days of vonoprazan with 14 days of omeprazole

Group 1: Vonoprazan (20mg/day), amoxicillin (1000mg/day), and clarithromycin 500 (mg/day). Group 2: Omeprazole (20mg/day), amoxicillin (1000mg/day), clarithromycin (500mg/day)

Similar remission for vonoprazan (97%) and omeprazole (93%)

Yes

34

Observational

Japan

-

1355

To determine if vonoprazan is a treatment alternative

Lansoprazole (30 mg twice daily) or rabeprazole (10 mg twice daily) or esomeprazole (2 mg twice daily) or vonoprazan (20mg twice daily),  amoxicillin (750mg twice daily), and clarithromycin (200-400mg twice daily) for seven days.

Similar remission for vonoprazan and PPIs

Yes*

35

Randomized clinical trial

Japan, China, South Korea, and Taiwan

-

531

To compare vonoprazan's and lansoprazole's efficacy and safety

Vonoprazan (20mg, twice daily), lansoprazole (30mg twice daily), bismuth salt (600mg twice daily), amoxicillin (1g twice daily), and clarithromycin (500mg twice daily) for two weeks.

Similar remission and safety for both drugs.  0% H. pylori emission with vonoprazan

Yes

36

Randomized clinical trial

Japan

-

87

To compare vonoprazan and rabeprazole

Vonoprazan (40mg/dia) or rabeprazole (20mg/day), amoxicillin (1500mg/day), metronidazole (500mg/day)

Similar remission

Same

37

Randomized clinical trial

Japan

-

63

To compare vonoprazan or PPI after the failure of first- and second-line therapy

Vonoprazan (20mg twice daily), amoxicillin (750mg twice daily), sitafloxacin (100mg twice daily), esomeprazole (20mg twice daily), or rabeprazole (10mg twice daily), or lansoprazole (30mg twice daily) or sitafloxacin (100 mg twice daily) for seven days

Vonoprazan was superior to PPI as a third-line treatment

Yes

38

Meta-analysis

Japan

18

-

To analyze vonoprazan's efficacy

Vonoprazan (20 mg/day) or PPI in association with amoxicillin (750mg/day) and clarithromycin 200mg or 400mg/day)

Superior remission with vonoprazan

Yes

39

Meta-analysis

China

14

14,636

To analyze vonoprazan's efficacy and safety compared to PPIs

Vonoprazan (20 mg/day) or PPI in association with amoxicillin (750mg/day) and clarithromycin 200mg or 400 mg/day)

92.6% remission with vonoprazan and 74.6% remission with PPI-based therapies

Yes

40

Meta-analysis

Indonesia

16

-

To analyze vonoprazan's efficacy

Vonoprazan (20 mg/day) or PPI in association with amoxicillin (750mg/day) and clarithromycin 200mg or 400mg/day)

Superior remission with vonoprazan

Yes

41

Meta-analysis

China

18

-

To compare vonoprazan and PPI in H. pylori, ulcer and GERD

Vonoprazan (20mg/day) or PPI in association with amoxicillin (750mg/day) and clarithromycin 200mg or 400mg/day)

Superior H. pylori remission with vonoprazan

Yes

42

Meta-analysis

China

3

897

To compare vonoprazan and PPI's efficacy and safety

Vonoprazan (20mg/day), amoxicillin (750mg/day), and clarithromycin (200-400mg twice daily)

Superior H. pylori remission and inferior adverse effects with vonoprazan

Yes

43

Table 3 Studies on Helicobacter pylori eradication using vonoprazan or proton pump inhibitors
Abbreviations: PPI, proton pump inhibitors; GERD, gastroesophageal reflux disease.

Primary-line treatment

Rokkas et al.30 selected 68 randomized trials with a total of 22.975 patients, comparing eight different first-line treatments and triple therapy with vonoprazan showing the highest SUCRA (surface under the cumulative ranking curve) value (92.4%).

Six of the seven meta-analysis reviews31,40–42,4 found that vonoprazan-based triple therapy was more effective than PPIs. However, in Yang et al.46 vonoprazan outperformed lansoprazole and rabeprazole but did not differ significantly from esomeprazole. Furthermore, Liu et al.23 demonstrated that vonoprazan could treat clarithromycin-resistant H. pylori.

Yang et al.55 looked at eight trials with a total of 2012 patients and found that vonoprazan was significantly more effective than PPIs in first-line treatment, both in intention-to-treat patients (RR, 1.14; 95% CI: 1.06-1.23; p=0.0006) and in per-protocol patients (RR, 1.12; 95% CI: 1.04-1.20; p=0.003).

Bunchorntavakul et al.34 included 122 patients on first-line vonoprazan and PPIs in randomized clinical trials. Vonoprazan was similar to PPIs (7-VAC and 14-OAC groups: 96.7% and 88.5%, p=0.083, respectively) in the analysis with the intention-to-treat and 98.3% and 93.1%, p=0.159, respectively, in the per protocol).  Hou et al.36 included 415 patients with H. Pylori, with vonoprazan eradicating 91.5% (193/211) for vonoprazan and 86.6% (177/204) for lansoprazole.

Tanabe et al.35 studied 1355 patients treated for H. pylori, of which 1143 received vonoprazan or PPIs. Vonoprazan was significantly more effective (p < 0.001) in eliminating H. pylori and was equally effective to PPI in treating clarithromycin susceptibility.

In Kusunoki et al.56 1172 patients received first-line treatment. H. pylori elimination was 86.9% (1,019/1,172) when given triple therapy, and 92.5% (384/415) with only vonoprazan. First-line eradication therapy worked significantly better for vonoprazan than for PPI-based therapy (OR 2.36; 95% CI: 1.55 to 3.56). 

Sue et al.57 looked at 147 patients with H. pylori, from which 106 patients were susceptible to clarithromycin. H. pylori eradication rates in patients receiving vonoprazan with intent-to-treat and per protocol were 87.3% (95% CI=75.5%-94.7%; 48/55) and 88.9% (95% CI=77.4%-95.8%; 48/54), respectively. The same rates of PPI patients were 76.5% (95% CI: 62.5%-87.2%; 39/51) and 86.7% (95% CI: =73.2%- 94.9%, 39/45).

Second-line treatment

Dong et al.40 revised 14 studies with 14,636 patients comparing vonoprazan with PPIs as a second-line triple therapy in which clarithromycin was replaced by metronidazole. The power of vonoprazan to eradicate H. pylori was not significantly different from PPIs (83.4% vs. 81.2%, P=0.79, OR 1.04; 95% CI: 0.77-1.42). Furthermore, the results of the per-protocol analysis were comparable to those of the intention-to-treat analysis (89.3% vs. 90.1%, P=0.06).

In Yang et al.46 five studies analyzing H. pylori second-line treatment indicated an eradication rate of over 90. However, this eradication rate was not significantly different from the use of PPIs.

Shinozaki et al.43 analyzed six observational studies totaling 6,664 patients treated with three drugs: amoxicillin (750 mg), metronidazole (250mg), and an acid blocker (vonoprazan 20mg, esomeprazole 20 mg, lansoprazole 30 mg, omeprazole 20mg, or rabeprazole 10mg) twice daily for seven days. H. pylori was eradicated in 91% of cases when vonoprazan was included in the regimen, compared to 88% when PPIs were used. Therefore, the authors considered vonoprazan-based therapy more effective than PPI-based regimens in treating H. pylori (OR 1.51; 95% CI: 1.27-1.81; p <0.001) with no heterogeneity (I2=0%).

Kusunoki et al.58 used 1329 patients with H. pylori for second-line therapy containing PPI or vonoprazan, amoxicillin, and metronidazole. The PPIs included esomeprazole (20mg), lansoprazole (30mg) and rabeprazole (10mg). The vonoprazan-based regimen was not superior to the PPI-based regimen for second-line eradication therapy. Nabeta et al.59 established a regimen containing metronidazole 250mg, amoxicillin 750mg, and an acid-suppressing drug (vonoprazan 20mg, lansoprazole 30mg, or rabeprazole 10mg) twice daily for seven days for H. pylori eradication. Vonoprazan-based regimen had a higher H. pylori elimination rate than PPI (90% vs. 85%, p=0.045;). Furthermore, in the per-protocol analysis, patients treated with vonoprazan had a higher success rate in eradicating H. pylori than patients under PPI (96 vs. 91%, p=0.008;).

Third-line treatment

In Nishizawa et al.33 twelve studies were analyzed and concluded that vonoprazan-sitafloxacin-amoxicillin treatment was significantly superior to PPI-sitafloxacin-amoxicillin (OR 6.00; 95% CI: 2.25-15.98; p <0.001). 

Sue et al.60 analyzed 58 patients treated with vonoprazan and PPI. However, no significant differences were observed in the intention-to-treat analysis (p=0.071). 

In the 19 studies considered in this systematic review, vonoprazan was equally or more effective (68.4%; 13/19) than PPIs in the first-, second-, and third-line treatment for H. pylori eradication. However, most studies were conducted in Asia, mainly in Japan, which may impose a regional bias in the results. It is known that the Japanese ethnicity has a higher incidence of gastrointestinal H. pylori-related cancer. In addition, Vonoprazan has been developed and used in Japan longer than in other countries, which may explain the various studies with the Japanese population. Thus, there is a need for new studies comparing vonoprazan and PPIs in non-Asian populations. Furthermore, vonoprazan and PPIs showed similar adverse effects, but no study directly compared their cost-effectiveness.

Conclusion

The literature shows divergent results regarding the treatment with vonoprazan for preventing bleeding and ulcers after ESD, GERD, and H. pylori eradication. Vonoprazan had a superior or equal result as PPIs in preventing bleeding and treating post-ESD ulcers. Moreover, in GERD, vonoprazan was a better treatment choice than PPIs in half of the studies, while the other half considered them equally effective. Finally, vonoprazan was more efficient in eradicating H. pylori than PPIs in 68.42% of the studies, showing vonoprazan's potential as an alternative to the current therapy. Lastly, it is worth emphasizing the need for multicenter studies to avoid implicit bias in the sample population.

Acknowledgments

No acknowledgments were necessary.

Conflicts of interest

The authors declare no conflict of interest.

Funding

None.

References

  1. FitzGerald R, Smith SM. An Overview of Helicobacter pylori Infection. Methods Mol Biol. 2021;2283:1–14.
  2. Yang X, Li Y, Sun Y, et al. Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases. Dig Dis Sci. 2018;63:302–311.
  3. Otake K, Sakurai Y, Nishida H, et al. Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438). Adv Ther. 2016;33:1140–1157.
  4. Miyazaki H, Igarashi A, Takeuchi T, et al. Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: A systematic review. J Gastroenterol Hepatol. 2019;34:1316–1328.
  5. Yoon JH, Kim YJ, Lee KN, et al. Effect on Bleeding Prevention of an Intravenous Proton Pump Inhibitor During the Fasting Period After Endoscopic Submucosal Dissection: a Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. J Gastrointest Surg. 2020;24:2596–2601.
  6. Marabotto E, Ziola S, Savarino V, et al. Vonoprazan Fumarate for the Treatment of Gastric Ulcers: A Short Review on Emerging Data. Clin Exp Gastroenterol. 2020;13:99–104.
  7. Scott DR, Marcus EA, Sachs G. Vonoprazan: MarKed Competition for PPIs? Dig Dis Sci. 2016;61:1783.
  8. Savarino E, Martinucci I, Furnari M, et al. Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations. Expert Opin Drug Metab Toxicol. 2016;12:1333–1341.
  9. Echizen H. The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016;55:409–418.
  10. Martinucci I, Blandizzi C, Bodini G, et al. Vonoprazan fumarate for the management of acid-related diseases. Expert Opin Pharmacother. 2017;18:1145–1152.
  11. Abe H, Hatta W, Ogata Y, et al. Prevention of delayed bleeding with vonoprazan in upper gastrointestinal endoscopic treatment. J Gastroenterol. 2021;56:640–650.
  12. Cheng Y, Liu J, Tan X, et al. Direct Comparison of the Efficacy and Safety of Vonoprazan Versus Proton-Pump Inhibitors for Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis. Digestive Diseases and Sciences. 2020 66:1 2020;66:19–28.
  13. Sakurai K, Suda H, Fujie S, et al. Short-Term Symptomatic Relief in Gastroesophageal Reflux Disease: A Comparative Study of Esomeprazole and Vonoprazan. Dig Dis Sci. 2019;64:815.
  14. Kambara H, Hosohata K, Nakatsuji T, et al. Safety profile of vonoprazan compared with proton pump inhibitors: insight from a pharmacovigilance study. Pharmazie. 2020;75:527–530.
  15. Miwa H, Igarashi A, Teng L, et al. Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease. J Gastroenterol. 2019;54:718–729.
  16. Akiyama J, Hosaka H, Kuribayashi S, et al. Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux. Digestion. 2020;101:174–183.
  17. Yang X, Li Y, Sun Y, et al. Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases. Dig Dis Sci. 2018;63:302–311.
  18. Shiratori Y, Niikura R, Ishii N, et al. Vonoprazan versus proton pump inhibitors for postendoscopic submucosal dissection bleeding in the stomach: a multicenter population-based comparative study. Gastrointest Endosc. 2022;95:72-79.e3.
  19. He HS, Li BY, Chen QT, et al. Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis. Med Sci Monit. 2019;25:1169–1176.
  20. Kang H, Kim BJ, Choi G, et al. Vonoprazan versus proton pump inhibitors for the management of gastric endoscopic submucosal dissection-induced artificial ulcer: A systematic review with meta-analysis. Medicine. 2019;98.
  21. Jaruvongvanich V, Poonsombudlert K, Ungprasert P. Vonoprazan versus proton-pump inhibitors for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30:1416–1421.
  22. Martin, Zhou Y, Meng CX, et al. Vonoprazan vs proton pump inhibitors in treating post-endoscopic submucosal dissection ulcers and preventing bleeding: A meta-analysis of randomized controlled trials and observational studies. Medicine. 2020;99.
  23. Liu C, Feng BC, Zhang Y, et al. The efficacy of vonoprazan for management of post-endoscopic submucosal dissection ulcers compared with proton pump inhibitors: A meta-analysis. J Dig Dis. 2019;20:503–511.
  24. Yang X, Li Y, Sun Y, et al. Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases. Dig Dis Sci. 2018;63:302–311.
    25. Hirai A, Takeuchi T, Takahashi Y, et al. Comparison of the Effects of Vonoprazan and Lansoprazole for Treating Endoscopic Submucosal Dissection-Induced Artificial Ulcers. Dig Dis Sci. 2018;63:974–981.
  25. Ishida T, Dohi O, Yamada S, et al. Clinical Outcomes of Vonoprazan-Treated Patients after Endoscopic Submucosal Dissection for Gastric Neoplasms: A Prospective Multicenter Observation Study. Digestion. 2021;102(3):386–396.
  26. Tsuchiya I, Kato Y, Tanida E, et al. Effect of vonoprazan on the treatment of artificial gastric ulcers after endoscopic submucosal dissection: Prospective randomized controlled trial. Dig Endosc. 2017;29(5):576–583.
  27. Komori H, Ueyama H, Nagahara A, et al. A prospective randomized trial of a potassium competitive acid blocker vs proton pump inhibitors on the effect of ulcer healing after endoscopic submucosal dissection of gastric neoplasia. J Int Med Res. 2019;47(4):1441–1452.
  28. Kawai D, Takenaka R, Ishiguro M, et al. Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucosal dissection: a randomized, open-label trial. BMC Gastroenterol. 2021;21(1):236.
  29. Rokkas T, Gisbert JP, Malfertheiner P, et al. Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis. Gastroenterology. 2021;161(2):495-507.e4.
  30. Jung YS, Kim EH, Park CH. Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication. Aliment Pharmacol Ther. 2017;46(2):106–114.
  31. Yang C, Li S, Huang T, et al. Effectiveness and safety of vonoprazan-based regimen for Helicobacter pylori eradication: A meta-analysis of randomized clinical trials. J Clin Pharm Ther. 2022;47(7):897–904.
  32. Nishizawa T, Munkjargal M, Ebinuma H, et al. Sitafloxacin for Third-Line Helicobacter pylori Eradication: A Systematic Review. J Clin Med. 2021;10(12):2722.
  33. Bunchorntavakul C, Buranathawornsom A. Randomized clinical trial: 7-day vonoprazan-based versus 14-day omeprazole-based triple therapy for Helicobacter pylori. J Gastroenterol Hepatol. 2021;36(12):3308–3313.
  34. Tanabe H, Yoshino K, Ando K, et al. Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. Ann Clin Microbiol Antimicrob. 2018;17(1):29.
  35. Hou X, Meng F, Wang J, et al. Vonoprazan non-inferior to lansoprazole in treating duodenal ulcer and eradicating Helicobacter pylori in Asian patients. J Gastroenterol Hepatol. 2022;37(7):1275–1283.
  36. Hojo M, Asaoka D, Takeda T, et al. Randomized controlled study on the effects of triple therapy including vonoprazan or rabeprazole for the second-line treatment of Helicobacter pylori infection. Therap Adv Gastroenterol. 2020;13.
  37. Sue S, Shibata W, Sasaki T, et al. Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori. J Gastroenterol Hepatol. 2019;34(4):686–692.
  38. Kiyotoki S, Nishikawa J, Sakaida I. Efficacy of Vonoprazan for Helicobacter pylori Eradication. Internal Medicine. 2020;59(2):153.
  39. Dong SQ, Singh TP, Wei X, et al. Review: A Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion? Helicobacter. 2017;22(6).
  40. Miftahussurur M, Putra BP, Yamaoka Y. The Potential Benefits of Vonoprazan as Helicobacter pylori Infection Therapy. Pharmaceuticals. 2020;13(10):1–14.
  41. Lyu QJ, Pu QH, Zhong XF, et al. Efficacy and Safety of Vonoprazan-Based versus Proton Pump Inhibitor-Based Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Clinical Trials. Biomed Res Int. 2019;2019.
  42. Shinozaki S, Kobayashi Y, Osawa H, et al. Effectiveness and Safety of Vonoprazan versus Proton Pump Inhibitors for Second-Line Helicobacter pylori Eradication Therapy: Systematic Review and Meta-Analysis. Digestion. 2021;102(3):319–325.
  43. He HS, Li BY, Chen QT, et al. Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis. Med Sci Monit. 2019;25:1169–1176.
  44. Miwa H, Igarashi A, Teng L, et al. Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease. J Gastroenterol. 2019;54(8):718–729.
  45. Yang X, Li Y, Sun Y, et al. Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases. Dig Dis Sci. 2018;63:302–311.
  46. Kang H, Kim BJ, Choi G, et al. Vonoprazan versus proton pump inhibitors for the management of gastric endoscopic submucosal dissection-induced artificial ulcer: A systematic review with meta-analysis. Medicine. 2019;98(24).
  47. Jaruvongvanich V, Poonsombudlert K, Ungprasert P. Vonoprazan versus proton-pump inhibitors for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30(12):1416–1421.
  48. Horikawa Y, Mizutamari H, Mimori N, et al. Short-term efficacy of potassium-competitive acid blocker following gastric endoscopic submucosal dissection: a propensity score analysis. Scand J Gastroenterol. 2018;53(2):243–251.
  49. Martin, Zhou Y, Meng CX, et al. Vonoprazan vs proton pump inhibitors in treating post-endoscopic submucosal dissection ulcers and preventing bleeding: A meta-analysis of randomized controlled trials and observational studies. Medicine. 2020;99()9:e19357.
  50. Wang J, Guo X, Ye C, et al. Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for endoscopic submucosal dissection-induced ulcers: A Meta-analysis. Internal Medicine. 2014;53(12):1243–1248.
  51. Ban H, Inatomi O, Murata M, et al. Vonoprazan vs lansoprazole for the treatment of artificial gastric ulcer after endoscopic submucosal dissection: a prospective randomized comparative study. J Clin Biochem Nutr. 2021;68(3):259–263.
  52. Yoshii S, Yamada T, Yamaguchi S, et al. Efficacy of vonoprazan for the prevention of bleeding after gastric endoscopic submucosal dissection with continuous use of antiplatelet agents. Endosc Int Open. 2020;8(4):E481–E487.
  53. Yang X, Li Y, Sun Y, et al. Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases. Dig Dis Sci. 2018;63(2):302–311.
  54. Yang C, Li S, Huang T, et al. Effectiveness and safety of vonoprazan-based regimen for Helicobacter pylori eradication: A meta-analysis of randomized clinical trials. J Clin Pharm Ther. 2022;47(7):897–904.
  55. Kusunoki M, Yuki M, Ishitobi H, et al. Effect of Age on Effectiveness of Vonoprazan in Triple Therapy for Helicobacter pylori Eradication. Intern Med. 2019;58(11):1549–1555.
  56. Sue S, Ogushi M, Arima I, et al. Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial. Helicobacter. 2018;23(2):e12456.
  57. Kusunoki M, Yuki M, Ishitobi H, et al. Effect of Age on Effectiveness of Vonoprazan in Triple Therapy for Helicobacter pylori Eradication. Intern Med. 2019;58(11):1549–1555.
  58. Nabeta H, Shinozaki S, Abe Y, et al. A Potassium-Competitive Acid Blocker-Based Regimen as Second-Line Therapy Improves Helicobacter pylori Eradication. Digestion. 2020;101(3):332–338.
  59. Sue S, Shibata W, Sasaki T, et al. Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori. J Gastroenterol Hepatol. 2019;34(4):686–692.
Creative Commons Attribution License

©2022 Silva, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.