Introduction
Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans, with conservative estimates suggesting that 50% of the world’s population is affected. Infection is more frequent and acquired at an earlier age in low-resource countries compared with developed countries.1 Once acquired, the infection persists and may or may not lead to gastro-duodenal disease. H. pylori infection is usually acquired during childhood.2 Risk factors for acquiring the infection include low socioeconomic status,3 an increasing number of siblings, and having an infected parent, especially an infected mother.4 In low-resource countries, where the majority of children are infected before the age of 10, the prevalence in adults exceeds 80% by age 50.5
About one-third of adults in Northern Europe and North America are infected, whereas infection rates in Southern and Eastern Europe, South America, and Asia are often higher than 50%.3
In Egypt, a study on school children found that the prevalence of H. pylori infection was 72.38%. The study also reported that children living in Upper Egypt had a higher infection rate than those in Giza and Cairo (96.7% vs. 61.9%, respectively), highlighting the influence of geographical location and socioeconomic status on infection rates.6
A more recent study conducted on 1,120 Egyptian patients by Abdelmonem et al. reported an H. pylori infection prevalence of 52% in the Nile Delta, with a prevalence rate of 41% among children.7
If left untreated, H. pylori infection can lead to serious complications, such as peptic ulcer disease and gastric cancer.8
Eradication of H. pylori has proven challenging due to the emergence of drug-resistant bacteria, the absence of a gold standard diagnostic method, and the ineffectiveness of current vaccines.9
Eradication rates with classical proton pump inhibitor (PPI)-based triple therapy have decreased below 80% in Europe and the USA due to rising Clarithromycin resistance.2,10,11H. pylori susceptibility to antibiotics is impacted by intra-gastric pH, which influences antibiotic stability and activity as well as the replication status of H. pylori.12 Acid-suppressive medications are essential in H. pylori treatment regimens, as they enhance antibiotic effectiveness.13 Some antibiotics require active H. pylori replication for optimal antimicrobial activity.14 Therefore, sustained control of intra-gastric pH may improve H. pylori eradication rates.15
It has been hypothesized that a more potent acid suppressant agent, such as vonoprazan, could increase the eradication rates of current regimens.16 Vonoprazan is a potassium-competitive acid blocker approved in several countries for treating H. pylori infection and other acid-related diseases. It increases intra-gastric pH more rapidly and potently than PPIs and maintains it more consistently, which has been associated with higher H. pylori eradication rates.17
Vonoprazan has the potential to optimize H. pylori therapy by improving gastric acid suppression, thereby enhancing antimicrobial activity. A meta-analysis of Asian trials found that the triple combination of vonoprazan, amoxicillin, and clarithromycin produced significantly higher eradication rates compared to PPI-based triple therapy, even among patients with clarithromycin-resistant strains (p < 0.001).18,19
This study aimed to compare the effectiveness of a vonoprazan-based eradication regimen versus a PPI-based eradication regimen for the eradication of H. pylori infection in both treatment-naïve and treatment-experienced Egyptian patients.
Discussion
Vonoprazan, a newly introduced P-CAB in H. pylori eradication regimens, has an efficacy that is not affected by meal ingestion, as its absorption rate is independent of meals. P-CABs are rapidly absorbed, with the time to reach maximum plasma concentration being less than 2 h after oral administration. After absorption, the half-life in plasma is up to 9 h for P-CABs, compared to approximately 2 h for conventional PPIs. Therefore, P-CABs remain in the bloodstream longer and can continuously block acid secretion.21 Consequently, the current study aimed to compare the efficacy of P-CABs versus PPIs, with identical antibiotic regimens, in the eradication of H. pylori infection in the Egyptian population. To our knowledge, this is the first study to address this research question in Egyptian patients.
Regarding the treatment outcomes among treatment-naïve patients in this study, in Arm 1, 34 out of 58 patients (58.6%) achieved H. pylori eradication according to ITT analysis, while the percentage was 64.2% according to PP analysis. In Arm 2, 29 out of 58 patients (50%) achieved H. pylori eradication according to ITT analysis, while the percentage was 56.9% according to PP analysis.
In comparison, a similar study on a Japanese cohort showed higher H. pylori eradication rates in the treatment-naïve P-CAB group (89.6%), whereas the treatment-naïve PPI group achieved 71.9% eradication according to ITT analysis.22
P-CABs demonstrated a higher success rate tendency among treatment-naïve H. pylori patients compared to the PPI-based group in the Japanese study, though the difference was not statistically significant. This result aligns with the findings of the current study, which also showed a higher tendency for eradication in treatment-naïve patients without a statistically significant difference.
Contrary to the current study’s findings, Yamada et al. concluded that P-CABs had a statistically significant higher success rate among treatment-naïve H. pylori patients compared to the PPI-based group (85.7% vs. 73% by ITT analysis, p-value => 0.001).23
Regarding the treatment outcomes among treatment-experienced patients in this study, in Arm 3, 29 out of 58 patients (50%) achieved H. pylori eradication according to ITT analysis, while the percentage was 72.5% according to PP analysis. In Arm 4, 25 out of 58 patients (43.1%) achieved H. pylori eradication according to ITT analysis, while the percentage was 59.5% according to PP analysis.
In comparison to these findings, Matsumoto et al.22 reported that in two groups of treatment-experienced patients, the introduction of P-CABs in a second-line eradication regimen resulted in 76.1% H. pylori eradication, while reuse of PPIs in a second-line regimen achieved eradication in 40.2% of cases.
Yamada et al.23 study, which assessed the efficacy of PPIs versus P-CABs in treatment-experienced H. pylori patients, reported that P-CABs achieved H. pylori eradication in 89.4% of patients according to ITT analysis, with a rate of 96.7% according to PP analysis. In comparison, PPIs achieved eradication in 89.9% of patients according to ITT analysis, with a rate of 92.8% according to PP analysis.
In agreement with the current study’s findings, Chey et al.24 reported data from the first Phase
Three clinical trial conducted in the USA and Europe to compare the efficacy and safety of vonoprazan-based triple and dual therapies versus PPI-based triple therapy for the eradication of H. pylori. A total of 1,064 treatment-naïve adult patients with H. pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin three times daily) or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary eradication rates (for non-resistant strains) were 84.7% for vonoprazan triple therapy, 78.5% for dual therapy, and 78.8% for lansoprazole triple therapy. In clarithromycin-resistant infections, eradication rates were 65.8% for vonoprazan triple therapy, 69.6% for dual therapy, and 31.9% for lansoprazole triple therapy.
When we consider the results of the current study alongside those from Japanese studies, we observe a trend toward higher eradication rates in the P-CAB treatment groups compared to the PPI-based groups, despite the absence of statistically significant differences between the drugs across the three studies. Contrary to the findings of the Yamada et al.23 study, the current study reports a higher percentage of dropouts, particularly within the treatment-experienced group (Arms 3 and 4). In contrast, in the treatment-naïve group (Arms 1 and 2), both studies show comparable dropout rates. Furthermore, regarding treatment adherence among the four study arms, it was found that patients in Arms 1 and 2 had an adherence rate of 94.8%, whereas those in Arms 3 and 4 had adherence rates of 77.6% and 84.5%, respectively. Thus, adherence appears to be higher in the triple therapy group than in the quadruple therapy group.
Regarding treatment-related side effects experienced by the participants in the current study, among the 116 recipients of vonoprazan-based treatments (Arms 1 and 3), one patient (0.9%) experienced a major event in the form of severe, intolerable gastric upset and vomiting, which led to hospitalization. Meanwhile, three patients (2.6%) experienced minor side effects such as nausea, gastric upset, vomiting, or diarrhea.
Among the 116 recipients of PPI-based treatments (Arms 2 and 4), five patients (4.3%) experienced minor side effects, such as nausea, gastric upset, vomiting, or diarrhea.
In comparison, Chey et al.24 reported that among 694 patients who received vonoprazan-based regimens, treatment-emergent adverse events were reported in 34.1% (118 of 346) and 29.9% (104 of 348) of vonoprazan triple and dual therapy groups, respectively, and in 34.5% (119 of 345) of the lansoprazole triple therapy group. Serious treatment-emergent adverse events occurred in 1.7% (6 of 346), 1.4% (5 of 348), and 0.9% (3 of 345). Treatment-related discontinuations occurred in 2.3% (8 of 346), 0.9% (3 of 348), and 1.2% (4 of 345) of patients in the vonoprazan triple, vonoprazan dual, and lansoprazole triple therapy groups, respectively. Overall, there were three deaths: two due to COVID-19 (one patient each on lansoprazole triple therapy and vonoprazan triple therapy) and one due to a fatal sudden cardiac arrest (a patient on vonoprazan triple therapy).The high dropout rates and low treatment adherence in the treatment-experienced groups in the current study could be attributed to polypharmacy, which may lead to noncompliance, in comparison to the treatment-naïve groups.
The higher success in eradication rates in the Japanese studies compared to the current study could be attributed to racial differences between Egyptian and Japanese patients. Additionally, the current study was conducted in 2023, unlike the Japanese studies, which were conducted in 2016. Over time, more aggressive, resistant H. pylori strains may have developed. According to Alboraie et al.,25 a percentage of 50% or less of the H. pylori population in Egypt is believed to harbor clarithromycin-resistant H. pylori strains, as evidenced by culture techniques. Another explanation for the difference in eradication rates between the current study and the Japanese studies is the difference in medications used in the studies.
Limitations of the current study include the following: The small number of participants in each arm, being a single-center study, the use of a single test (H. pylori stool antigen test) for initial diagnosis and for confirming eradication of H. pylori after treatment, and being a non-controlled, non-randomized study.
H. pylori infection and the efficacy of eradication regimens were assessed using the stool antigen test because this test is more widely available, cheaper, and more accurate in Egypt compared to other non-invasive tests as the urea breath test (UBT), rapid urease test (RUT), and serology. The stool antigen test is much more affordable and accessible in Egypt, and it is non-invasive compared to RUT and histology. Kazemi et al.26 conducted a study comparing the validity of five diagnostic tests for H. pylori: stool antigen test, UBT, RUT, serology, and histology. A total of 94 patients eligible for H. pylori testing were enrolled, and all five tests were performed for each patient. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the Receiver Operating Curve (ROC) curve for these tests are as below, respectively. Histology: 89%, 78%, 93%, 91%, 85%, and 0.881; RUT: 93%, 75%, 95%, 94%, 86%, and 0.831; serology: 50%, 54%, 46%, 61%, 52%, and 0.563; stool antigen test: 96%, 83%, 98%, 96%, 91%, and 0.897; UBT: 89%, 73%, 92%, 90%, 82%, and 0.892. The authors concluded that the H. pylori stool antigen test is the most accurate diagnostic tool for H. pylori.
The lack of a control and placebo arm in the current study is justified as this was a comparative non-inferiority study conducted to assess the efficacy of P-CABs versus PPIs in primary and secondary eradication regimens for H. pylori, being the first of its kind in Egypt. Although the design of this study is considered one of its limitations, the results provide a rationale for conducting a placebo-controlled, randomized study on Egyptian patients in the future.