Vonoprazan, a potent inhibitor of gastric acid secretion, is a recently introduced drug. It is debated to be better than or equal to proton pump inhibitors (PPIs) in the treatment of acid-based disorders and Endoscopic Submucosal Dissesction (ESD) induced ulcers. However, its efficacy regarding bleeding control, healing, and gastrointestinal tract (GIT) perforation after ulceration is not been sufficiently studied. The purpose of this study is to determine the efficacy of vonoprazan vs lansoprazole and to compare the side effect profile of both drugs. Data was sourced from PubMed, Google Scholar, and Cochrane databases. The initial search revealed 51 studies. After exclusion, 9 were included. All included studies were randomized controlled trials (RCTs) covering post-ESD treatment with Vonoprazan vs Lansoprazole over a period of 7 years (2016 to 2022), with sample sizes ranging from 14 to 250 subjects. The mean age of subjects was 65.02 years. The diagnostic modality was endoscopy. Study quality was calculated using the Modified Jadad or Oxford Scale. The pooled odds ratio of vonoprazan vs lansoprazole for ulcer healing rate was 1.34 (95% confidence interval [CI],1.00-1.79, I2=50%) with a statistically significant p-value of 0.05. The pooled Odds ratio of vonoprazan vs lansoprazole for bleeding control was 0.55 (95% CI, 0.24-1.27, I2=12%) with a p-value of 0.16, and that of vonoprazan vs lansoprazole for perforation was 1.49 (95% CI, 0.44-5.02, I2=0%), with a p-value of 0.52. Our study concluded that lansoprazole has a better ulcer healing rate than vonoprazan, while both have comparable bleeding and perforation control.

Vonoprazan, Lansoprazole, Gastrointestinal tract (GIT), Ulcer, Randomized controlled trials (RCTs), Endoscopy, Bleeding.

Gastric and Duodenal ulcers have become increasingly common in recent years, owing either to increased acid secretion or decreased defense mechanisms of the mucosa [1]. The introduction of acid suppression since the 1970s has transformed the treatment of these acid-based gastrointestinal disorders [2]. PPIs have been the treatment of choice for many years. However, they come with their drawbacks and sometimes are refractory in treatment, so a newer class of acid suppressors called Potassium-competitive acid blockers (P-CABs) was developed, which was expected to have a better side effect profile [3].

ESD is a procedure developed in the early 2000s for the resection of mucosal pathologies and, in recent years, it has been widely implemented in Asian countries [4]. However, certain complications may follow in the post-operative period following ESD, which include Hemorrhage, Perforation, and Stenosis [5]. A hemorrhage is a serious post-operative complication and is defined as bleeding that develops within 4 weeks of ESD [6].

Multiple guidelines have recommended the use of PPIs for controlling post-ESD bleeding [7,8,9]. PPIs also improve ESD-induced ulcer healing rate by decreasing gastric acid secretion [10]. A study shows that PPIs should be given for a minimum of 2 weeks post-ESD to promote effective ulcer healing without increasing any adverse effects [11].  However, the CYP2C19 polymorphisms of PPIs were found to alter their pharmacokinetic and pharmacodynamic properties, resulting in variable outcomes of therapy [12]. An alternate drug is needed with more stable pharmacokinetic and pharmacodynamic properties.

Vonoprazan is a potassium-competitive acid blocker that was introduced in February 2015 [13]. It rapidly reduces gastric acid levels and maintains a steady state for 24 hours, thus offering a long-lasting acid suppression [14]. Vonoprazan has proved to be an effective drug for the control of delayed bleeding in post-ESD ulcers by reducing the chances of delayed bleeding in ulcers >2cm, those with a scar, and those located in the antrum [15].

Vonoprazan and Lansoprazole have been compared in studies to determine the drug with better outcomes. A study showed that, inspite of vonoprazan having a faster healing rate in the initial post-ESD period, which was 4 weeks, and PPIs having better healing at 8 weeks, the overall ESD-induced ulcer shrinkage rate and control of bleeding were similar for both drugs [16]. Another study comparing Vonoprazan with Lansoprazole showed no significant difference in ulcer shrinkage rate between the two drugs [17]. While in other settings, Vonoprazon has been found to have better bleeding control post-ESD [18]. There is a need to further evaluate the two drugs in different populations and clinical settings. So, we conducted a meta-analysis that included randomized and non-randomized control trials on patients having any kind of ulcers in the GIT. These patients were aged between 16 and 70 years. Vanoprazan/Lansoprazole was administered to these patients, and a follow-up of a minimum of 7 days was done to determine the control of these drugs on disease progression and their side effects.

This systematic review and meta-analysis were done using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [19].

Eligibility criteria
Studies were eligible with consideration of the following inclusion criteria: (1) published full text and in the English language, (2) patients with a GIT ulcer were included, and (3) ulcer reduction rate and bleeding control after endoscopic submucosal dissection was reported with the inclusion of adult (age ≥20 years). (4) The study was included only if it was an RCT. Moreover, studies were carefully assessed if they had provided a comparison between Lansoprazole and Vonoprazan, separately, and were excluded if not. Articles were excluded if they were reviews, editorials, or case reports. The following Table 1 shows the patient population, intervention, comparator, outcomes, timing, and setting (PICOTS) criteria used to assess the eligibility of the studies.

Table 1: PICOTS criteria

Search Strategy & Study Selection
A systematic literature search was conducted using PubMed, Google Scholar and Cochrane databases with the following subject keywords and their MeSH terms: ‘Vonoprazan’, ‘Lansoprazole,’ ‘Gastrointestinal Tract Ulcers,’ ‘ESD induced ulcers,’ ‘Gastric ulcers,’ ‘Duodenal Ulcers,’ ‘PPIs’ and ‘P-CABs’ and these were combined with Boolean Operator such as OR/AND. This study was carried on for almost two months from July 27, 2022, to September 24, 2022.

Studies were initially shortlisted based on title and abstract, after which the full text was assessed for eligibility. References of the selected studies were also reviewed thoroughly to prevent any risk of selection bias.

Data Collection Process
Two authors separately reviewed and extracted data from included records, separately using the online systematic review tool: CADIMA. Disagreements were resolved by involving the third author deciding the extraction process according to our study criteria.

Data Items
Data extraction of the relevant studies included the first author, year of publication, type of study (cohort or RCT), study follow-up time, and the total number of patients who underwent treatment for any kind of ulcer treatment. Baseline characteristics and indications for ulcer treatment were also extracted. Primary outcomes of 7-day ulcer reduction and bleeding control rates were extracted by careful screening of tables and results of the individual studies. We only included secondary outcomes if three or more studies reported them. Details are present in the Table.1

Risk of bias in individual studies
Assessment of risk of bias quality assessment of all the randomized controlled studies was done using the oxford quality scoring or Jadad scale. It was done both at the study level and the outcome level. The outcome level bias was assessed using the funnel plot made by the Review Manager. It determines the authenticity of the synthesis. The principal measures were the odds ratio and the difference in means.

Synthesis of Results
The systematic review was done using the CADIMA tool for systematic reviews. All the extracted data were statistically analyzed using the Review Manager. Ulcer healing rate and all the secondary outcomes (delayed bleeding time and perforation) were pooled using both random and fixed effects models. The I² statistic was used to analyze the heterogeneity, with a value of >75% labeled as severe heterogeneity of the data. In addition to that, we also conducted a multivariate meta-regression analysis to assess the association between the odds ratio and vonprazan and lansoprazole in post-ESD ulcer patients.

Risk of bias in studies
A funnel plot was constructed using Review Manager for assessment of the risk of bias in studies. There was a small publication bias found in the included studies as represented by the funnel plot shown below. The funnel plot shown (Figure 1) is asymmetrical as the studies are not evenly distributed on both sides of the plot.

Figure 1: Funnel plot for assessment of publication bias

Study Selection
The initial search revealed 51 studies. After exclusions, 9 studies, published between 2016 and 2022, were included in a systematic review and 8 studies included meta-analysis. The following PRISMA flow diagram (Figure 2) shows the studies excluded at each step of study selection.

Figure 2: PRISMA flow diagram

Primary Outcome
Ulcer healing rate/shrinkage ratio: The pooled odds ratio of Vonoprazan vs Lansoprazole for ulcer healing rate was 1.34 (95% CI,1.00-1.79, I²=50%), which was statistically significant with a p-value of 0.05 as shown in Figure 3.

Figure 3: Ulcer healing rate/shrinkage ratio

Secondary Outcome
Bleeding control: The pooled odds ratio of Vonoprazan vs Lansoprazole for bleeding control was 0.55 (95% CI, 0.24-1.27, I²=12%), which was insignificant with a p-value of 0.16 as indicated in Figure 4, studies reporting the bleeding control.

Figure 4: Bleeding control

Perforation: The pooled odds ratio of Vonoprazan vs Lansoprazole for Perforation was 1.49 (95% CI, 0.44-5.02, I²=0%,) which was insignificant with a p-value of 0.52 as indicated in Figure 5, studies reporting the perforation.

Figure 5: Perforation

Table 2: Data extraction sheet

The debate about Vonoprazan, a potent inhibitor of gastric acid secretion, being better than PPIs, one of the most commonly prescribed groups of medications, in the treatment of acid-based disorders or ESD is far from over [20]. A lot of clinical trials have established the fact that vonoprazan is non-inferior, if not superior, to all other kinds of medications used in gastric acid-induced disorders while having a better side effect profile as well [21]. Despite all the trials done on the drug, its efficacy regarding ulcer healing, bleeding control, and gastrointestinal perforation for ulcers due to ESD remains unclear [22]. Therefore, a systematic review and meta-analysis were conducted to understand the cumulative result of these individual trials.

ESD is a widely used tool in Asia and has been gaining popularity in other parts of the world as well. Which is why most of our studies have been done in Japan and China [23]. ESD has significantly reduced morbidity and mortality in patients, in comparison to the surgical procedures used in the past [24]. The efficacy of ESD is determined by postoperative ulcer healing, bleeding control, and several other factors [25].  To prevent these postoperative side effects and increase the efficacy of this procedure, potent acid inhibition is required [26]. PPIs have always been the mainstay of treatment for acid inhibition, all over the world [27]. Potassium-competitive acid blocker(P-CAB), a newly discovered drug group for acid inhibition, is expected to do better than even PPIs [28].

Our study concluded that Lansoprazole (PPI) has a significantly superior ulcer healing rate in ESD-induced gastric ulcers, as compared to Vonoprazan (P-CAB). In contrast to the studies done before, which concluded that the Shrinkage ratio/Ulcer Healing Ratio is similar in Vonoprazan and Lansoprazole [22,29,30,31]. Our study determined that Lansoprazole is superior as far as the shrinkage ratio is concerned. Our study also negates the previously presented evidence that Vonoprazan has a better ulcer healing ratio as compared to lansoprazole [32]. This might be due to the fact that there is no clinically significant effect of CYP2C19 polymorphisms on vanoprazazan. Within 4 hours of administration, vonoprazan starts exerting its acid inhibitory effect by raising intragastric pH to 4, and the acid suppression sustains for 24 hours [33]. Conversely, PPIs have clinically significant effects of CYP2C19 polymorphism (CYP2C19 IMs and PMs having better efficacy than NMs) and a half-life of up to 5 hours, due to which they need to be administered two to three times a day [34].

Our study showed that Vonoprazan and Lansoprazole had equal efficacy in controlling post-ESD bleeding, as supported by the work done previously as well [29,35]. It also disapproves of the work of previous studies, stating the superiority of lansoprazole [22]. Similarly, our study demonstrated that Vonoprazan and Lansoprazole have no significant difference in controlling perforation, which was in accordance with the previous data [22]. However, only 5 studies were used to assess these two drugs for bleeding control, and only 4 studies could be assessed for perforation. There is a need to include a larger number of studies on more diverse populations around the world, so the comparison between the two classes of drugs can be generalized better.

The limitations of the study are 1) Only 9 RCTs could be included in our study after eligibility assessment, and most of them were conducted in Japan. Including a larger and more generalized population may show results different from our study. 2) The polymorphisms of CYP2C19 could not be assessed in our study, which may have altered the results. 3)The difference in post-ESD ulcer sizes may yield variable results. The sizes were not assessed in our study. 4) Subjects who were on medications like anticoagulants, antiplatelets, and steroids should have been excluded from our study, as the complications resulting from their use could have varied the results.

Our study showed that Lansoprazole had better ulcer healing and shrinkage ratio as compared to Vonoprazan. Moreover, both Vonoprazan and Lansoprazole had similar efficacy in controlling post-ESD bleeding and perforation. This study contributes to a better understanding of the efficacy and side effect profile of the newer P-CAB, Vanoprazan, as compared to the traditional PPIs. It further encourages healthcare providers to administer and study this drug’s efficacy in various other populations, including more subjects.

The authors, Ameer Hamza Mahmood, Nehala Nooz, and Syed Muhammad Jawad Zaidi, extend their gratitude to all individuals who contributed to the development of this manuscript.

The authors declare that no financial funding was received.

Corresponding Author:
Ameer Hamza Mahmood-ul-Hassan
Department of Medicine
Rawalpindi Medical University, Lahore, Punjab, Pakistan
Email: zamziorpion@gmail.com

Co-Authors:
Nehala Nooz, Syed Muhammad Jawad Zaidi
Department of Medicine
Rawalpindi Medical University, Lahore, Punjab, Pakistan

Syed Muhammad Jawad Zaidi: Investigation, All authors contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles. They were collectively involved in the writing – original draft preparation and writing – review & editing to refine the manuscript. Additionally, all authors participated in the Supervision of the work, ensuring accuracy and completeness. The final manuscript was approved by all named authors for submission to the journal.

Not applicable

None

Not reported

https://doi.org/10.63096/medtigo3062239

Ameer Hamza M-ul-H, Nehala N, Jawad Zaidi SM. Vonoprazan vs Lansoprazole in Gastrointestinal Tract Ulcers: A Systematic Review and Meta-Analysis. medtigo J Med. 2024;2(3):e3062239. doi:10.63096/medtigo3062239 Crossref