Comparison of Helicobacter pylori Eradication Rates Using Standard Triple Therapy and Sequential Therapy

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Korean J Helicobacter Up Gastrointest Res. 2023;23(4):277-282

Publication date (electronic) : 2023 December 8

doi : https://doi.org/10.7704/kjhugr.2023.0042

Yuri Kim, Ji Yong Ahn, Hwoon-Yong Jung, Jin Hee Noh, Hee Kyong Na, Kee Wook Jung, Jeong Hoon Lee, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee

Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea

Corresponding author Hwoon-Yong Jung, MD, PhD Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505, Korea E-mail: hyjung@amc.seoul.kr

Received 2023 August 14; Revised 2023 September 3; Accepted 2023 September 4.

Abstract

INTRODUCTION

Helicobacter pylori is an established etiological factor for peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer[1]. The bacterium is known to have affected approximately 50% of the global population, with a notably higher prevalence in developing countries [1,2]. Standard triple therapy (STT), comprising a proton pump inhibitor (PPI), clarithromycin, and amoxicillin, has traditionally been considered as the gold standard regimen for H. pylori eradication (HPE) in many regions of the world [3-5]. However, suboptimal eradication rates and instances of treatment failure have progressively escalated, reaching an unacceptable level [6-10]. In response, sequential therapy (SQ) has emerged as a promising approach to counteract the elevated levels of antibiotic resistance[11]. This novel regimen involves a distinctive sequence of antibiotic administration: a 5-day course of amoxicillin followed by 5-day course of clarithromycin and metronidazole, supplemented by 10 consecutive days of PPI intake. Following its initial implementation in Italy, several studies have reported higher eradication rates for SQ than that of the 7-day STT [12-16]. However, existing data present conflicting results regarding the efficacy of eradication rates, reporting no significant difference between the two treatment regimens [17,18]. Therefore, we conducted a retrospective analysis of patients who underwent H. pylori treatment between July 2013 and August 2017 at a single tertiary hospital. In this study, we aimed to provide insights into the outcomes related to eradication rates and adverse events associated with the use of the 7-day STT and SQ.

METHODS

Patients

We retrospectively analyzed consecutive data collected from patients who underwent eradication therapy for H. pylori infection and subsequent 13C-urea breath tests (UBT) at Asan Medical Center between July 2013 and August 2017 (Fig. 1). The study included only patients who had not previously received HPE treatment and for whom eradication was performed under the direction of a single physician. Among the initial 836 patients who underwent STT or SQ eradication therapy, 47 were excluded from the analysis due to a history of gastric surgery (n=19), previous eradication therapy (n=21), non-standard regimen use (n=6), or insufficient data (n=1). Among the remaining 789 patients, 378 received STT for 7 days as their first-line HPE treatment (STT group) and 411 received SQ for 10 days (SQ group). For these patients, clinical data including eradication indications, eradication rates, medication compliance, treatment-related adverse events, and family history of gastric cancer were retrospectively reviewed. Patients were requested to return at the end of therapy for an assessment of compliance and adverse events.

Fig. 1.

Patient inclusion flowchart. The flowchart depicting patient inclusion is provided for reference. H. pylori, Helicobacter pylori; STG, subtotal gastrectomy; HPE, Helicobacter pylori eradication.

RESULTS

Baseline characteristics of the patients

Table 1 presents the baseline demographic and clinical characteristics of the included patients. The median age and sex distribution in the SQ group were comparable to those in the STT group. The most common indication for eradication therapy in both groups was endoscopic resection of early gastric cancer or adenoma, accounting for 66.1% and 69.8% of patients in the STT and SQ groups, respectively. No significant disparity was observed in the indications for eradication therapy between the two groups.

Table 1.

Baseline characteristics of the study patients

HPE rates

Fig. 1 illustrates flowchart depicting patient inclusion in the study. Among the 378 patients in the STT group, 4 (1.1%) were non-compliant, and compliance data were absent for 8 (2.1%) patients. In the SQ group (n=411), 4 (1.0%) patients exhibited <90% compliance, and data were unavailable for another 4 patients (1.0%). Treatment compliance was not significantly different between the two groups (STT: 96.8% vs. SQ: 98.1%; p= 0.380). Notably, the eradication rate in the SQ group surpassed that in the STT group (84.7% vs. 74.1%, respectively; p<0.001) (Table 2).

Table 2.

Comparison of eradication rates between sequential therapy and standard triple therapy

Adverse events during eradication therapy

Table 3 outlines the adverse events reported during HPE. The incidence of adverse events was significantly higher in the SQ group than that in the STT group (16.8% vs. 11.4%, respectively; p=0.010). The most prevalent adverse events in both groups were abdominal discomfort and pain (STT: 5.6%; SQ: 6.3%). The distribution of specific adverse events was comparable between the two groups. All patients who experienced adverse events exhibited mild symptoms, and none required additional treatment or discontinuation of HPE therapy due to these events.

Table 3.

Adverse events of Helicobacter pylori eradication treatments

Quadruple therapy outcomes in treatment-failure patients

In the STT group, eradication therapy was ineffective in 98 patients, whereas the SQ group had 63 cases of treatment failure. Among the 98 treatment-failure patients in the STT group, 79 received quadruple therapy as a second-line regimen; among them, 73 achieved successful eradication. In contrast, the SQ group displayed a notably lower eradication rate (77.3% vs. 92.4%, respectively; p=0.028) (Fig. 2). The overall eradication rates for both first- and second-line HPE regimens were calculated for the STT and SQ groups, yielding results of 98.3% (353/359) and 97.4% (382/392) (p=0.560) (Fig. 3).

Fig. 2.

Results of the second-line Helicobacter pylori eradication in patients with first-line treatment failure. A summary of the outcomes of second-line Helicobacter pylori eradication (HPE) treatment based on the initial first-line HPE regimen for patients who experienced first-line therapy failure. Notably, the success rate in the sequential therapy group is significantly lower than that in the triple therapy group (p=0.028).

Fig. 3.

Overall success rates of HPE. Comparison of the comprehensive success rates of HPE between the triple and sequential therapy groups. HPE, Helicobacter pylori eradication.

DISCUSSION

In this study, we compared the eradication efficacies of the 7-day STT and SQ, which are both representative first-line treatment regimens for HPE in Korea. Our findings revealed that SQ had a significantly higher eradication rate than that of the 7-day STT, and it did not exhibit a decrease in compliance when used as a first-line treatment for H. pylori infection. STT has historically been the recommended as a primary treatment regimen in multiple guidelines, including the Guidelines for the Diagnosis and Treatment of Helicobacter pylori Infection published in 2013 by the Korean College of Helicobacter and Upper Gastrointestinal Research [19]. However, numerous reports have indicated a global decline in the eradication rate (<80%) associated with STT [6,8,9]. Since its introduction into the Korean market in the 1990s, clarithromycin has been the cornerstone of HPE therapy, administered in combination with a PPI to counteract the acidic gastric environment [20]. Nevertheless, a surge in clarithromycin-resistant H. pylori strains has emerged as a key contributor to treatment failures. Recent studies have identified that clarithromycin resistance rates in Korea range from 17.8% to 31.0% [21,22]. Consequently, the latest revision of the Helicobacter pylori infection guidelines in Korea recommends not only a 14-day triple therapy but also non-bismuth quadruple therapy, including SQ, as the first-line HPE regimen [3].

The superiority of SQ has been demonstrated in studies conducted across Asian and European countries since its introduction by Zullo et al. [11] in 2000 [11,23-26]. Eradication rates may vary by geographical region owing to the differences in antibiotic resistance patterns; however, in the majority of these studies, SQ consistently exhibited higher eradication rates (81.8%–94.2% in an intention-to-treat [ITT] analysis) than that of the standard 7-day STT (70.0%–74.3% in an ITT analysis). In line with these prior investigations, our study demonstrated an eradication rate of 84.7% for the SQ group, surpassing the rate observed for the STT group. The theoretical advantages of SQ include the administration of amoxicillin before that of clarithromycin and metronidazole during the first 5 days, which may lower H. pylori density in the stomach, potentially enhancing the efficacy of clarithromycin and metronidazole. Additionally, the action of amoxicillin as a cell wall synthesis inhibitor could potentially explain the inhibition of efflux channel production, a known mechanism of clarithromycin resistance [27].

Our study revealed that patients in the SQ group experienced more antibiotic-related adverse events (16.8%) than those of patients in the STT group (11.4%); abdominal discomfort and pain were the most common adverse events in both the groups. However, all adverse events were mild in nature, and none of the patients required hospitalization or therapy discontinuation owing to symptoms. Considering the risk-benefit balance between the therapeutic efficacy and complication rates of the two regimens, SQ remains a viable and effective treatment approach.

Although the first-line treatment eradication rate was notably higher in the SQ group than in the STT group, the second-line eradication rate (involving bismuth-based quadruple therapy for patients who failed the initial treatment) was lower in the SQ group. This may be attributed to the emergence of metronidazole resistance among patients who received SQ. Nevertheless, given the limited number of patients undergoing second-line eradication compared with the total cohort, this result may be subjected to statistical errors due to the small sample size. Furthermore, this disparity was mitigated when the first- and second-line treatment results were combined to calculate the overall eradication efficacy. To address this issue, future studies should encompass larger patient populations and include antibiotic susceptibility testing.

The limitations of our study included the retrospective study design and data collection at a single institution. Moreover, the absence of antibiotic resistance data hindered a comprehensive understanding of the exact mechanisms underlying the higher eradication rate in the SQ group than in the STT group. Additionally, current guidelines suggest a 14-day triple therapy in the absence of antibiotic susceptibility testing, necessitating further research for patients treated with 14-day triple therapy and SQ. Finally, further investigations should examine whether the efficacy and cost-effectiveness of SQ are superior to those of other options, such as concomitant therapy or bismuth quadruple therapy.

In conclusion, our findings supported the superiority of SQ over a 7-day STT as a first-line treatment for H. pylori infections. SQ has the potential to serve as a substitute for 7-day STT in treatment-naïve patients, particularly in medical settings where antibiotic susceptibility testing may be limited.

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