Bismuth-Based Quadruple Therapy for Clarithromycin-Resistant Helicobacter pylori Infection: Effectiveness and Cost-Efficiency

Clarithromycin-based triple therapy (CTT) is widely used for empirical first-line eradication of Helicobacter pylori. However, the efficacy of empirical CTT has gradually decreased with the increase in antibiotic resistance. Guidelines in Europe and the U.S. state that CTT is no longer recommended as the first-line therapy in areas with >15% clarithromycin resistance.^1,2 A recent study showed that the resistance rate against clarithromycin was 17.8% and eradication rate of empirical CTT was 71.6% in Korea.³ Therefore, finding an optimized, cost-effective, and tailored therapy according to clarithromycin resistance is of paramount importance.

In the latest issue of Gut and Liver, Seo et al.⁴ compared both the efficacy and cost-effectiveness of tailored therapy as a first-line treatment using sequencing-based clarithromycin resistance testing. Eradication rates of the 14-day bismuth-based quadruple therapy (BQT) were not significantly different from that of 14-day metronidazole-intensified triple therapy (MIT) in an intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but were significantly higher in the per-protocol analysis (95.1% vs 76.4%, p=0.001). Current Korean guidelines recommend 7-day proton pump inhibitor, amoxicillin, metronidazole (PAM) or 10- to 14-day BQT for clarithromycin-resistant H. pylori infection.⁵ However, 7-day PAM showed a significantly lower eradication rate owing to a high resistance rate against metronidazole. Metronidazole resistance is generally overcome by increasing the dose or treatment duration. In this study, eradication rate of 14-day MIT was not significantly different from that of a previous 7-day PAM study.⁶ In contrast, intention-to-treat and per-protocol eradication rates with 14-day BQT were 80.4% and 95.1%, respectively, reaching the recommended target rate for first-line treatment. There were no significant differences in non-compliance and prevalence of side effects between the BQT and PAM groups. Thus, 14-day BQT is an effective first-line therapy for clarithromycin-resistant H. pylori infections.

In this study,⁴ cost-effectiveness analyses of tailored therapy were compared with empirical CTT in first-line and second-line therapies using incremental cost-effectiveness ratio. BQT is more cost-effective than MIT. However, cost-effectiveness analysis showed an increased cost of tailored therapy compared to empirical CTT. The incremental cost-effectiveness ratio was higher in the BQT of second-line rescue therapy than in empirical CTT. This is because the sequencing-based clarithromycin resistance test (USD 57.5) used for tailored therapy is more expensive than the CLO test (USD 9.3) used for empirical therapy. When comparing regimens, cost-effectiveness is determined by efficacy of the regimen and not by its cost. Therefore, acceptance will likely be owing to socioeconomic costs, increasing antibiotic resistance, and disease prevention, whilst minimizing further utilization of healthcare resources, and eradicating H. pylori by saving on treatment costs.

In summary, 14-day BQT showed a higher eradication rate in per-protocol analysis and a comparable incidence of side effects to 14-day MIT as a first-line treatment, according to the sequencing-based clarithromycin resistance test. Moreover, it may be more cost-effective than a 14-day MIT. Tailored therapy may be increasingly used as a first-line treatment for H. pylori, and BQT should be recommended for clarithromycin-resistant H. pylori infection.