Effectively eradicating Helicobacter pylori

In 2015, Helicobacter pylori gastritis was formally recognised as an infectious disease worldwide. This meant that every patient infected with H. pylori should be treated.

New network meta-analysis on eight common first-line treatments

In 2015, Helicobacter pylori (H. pylori) gastritis was formally recognised as an infectious disease worldwide.1 A triviality, one might say, more than 30 years after the bacterium was recognised as the cause of gastric ulcer, but at least the 2015 statement simultaneously meant that every patient infected with H. pylori should be treated. Finally, in 2020, the Taipei Global Consensus emphasised the importance of H. pylori eradication in reducing gastric cancer mortality.2 So there is both a need and an obligation to eradicate H. pylori.

However justified this demand may be, it is counteracted by the realities of treatment. Compared to other infectious diseases, the success of H. pylori therapy is limited - despite numerous consensus conferences that have tried to recommend an optimal therapy.3

Current meta-analysis on the success of the eight widely used first-line treatments

This generally unsatisfactory situation has now prompted a group of scientists from the European Helicobacter and Microbiota Study Group (EHMSG) to conduct a network meta-analysis (NMA) comparing the effectiveness of the eight widely used first-line treatments for the eradication of H. pylori.4

These treatment regimens were:

  1. Concomitant quadruple bismuth treatment: proton-pump inhibitors (PPIs), bismuth and 2 antibiotics (mostly amoxicillin and clarithromycin)
  2. Concomitant quadruple non-bismuth treatment: PPI, amoxicillin, clarithromycin and metronidazole
  3. High dose amoxicillin double treatment: PPI and high dose amoxicillin
  4. Levofloxacin triple treatment: PPI, amoxicillin and levofloxacin
  5. Reverse hybrid therapy: PPI and amoxicillin for 14 days and clarithromycin and metronidazole for the first seven days
  6. Sequential quadruple treatment: PPI and amoxicillin for the first 5-7 days plus PPI and two antibiotics (clarithromycin, metronidazole; but also levofloxacin or tetracycline)
  7. Standard triple treatment: PPI, amoxicillin, clarithromycin
  8. Vonoprazan triple therapy: combination of the proton-pump inhibitor vonoprazan, currently only approved in Japan, with amoxicillin and clarithromycin

Led by Theodore Rokkas from the Henry Dunant Hospital in Athens, the researchers evaluated a total of 68 randomised controlled trials conducted in different regions of the world. They used an improved evaluation method called network meta-analysis (NMA).

Vonoprazan triple therapy best, levofloxacin triple treatment in western countries

The analysis showed that vonoprazan triple therapy and reverse hybrid therapy were the only first-line treatments to achieve eradication rates above 90%. This means that they were clearly superior to the other therapies in some cases. However, vonoprazan is currently only approved in Japan. According to the authors of the study, the high resistance of H. pylori to clarithromycin there has also led to a decline in the effectiveness of the therapy, with eradication rates < 90%.4 The classic triple treatment (standard triple treatment) proved to be the least effective form of therapy in the study.

In general, geographical differences between the common H. pylori strains play a significant role in the efficiency of the treatment forms. In western countries, for example, levofloxacin triple treatment produced the best results. This is remarkable because a consensus conference in 2018 recommended that this form of therapy should not be used empirically, but only after its regional efficacy has been proven.5 Against this background, various scientists are calling for "antimicrobial stewardship" to monitor the use of antibiotics and limit it to therapies that have been proven to be locally optimised and highly effective.3

The study also produced an interesting result on the cause of the comparatively low effectiveness of the classic triple therapy. It was shown that this had led to higher eradication rates in studies conducted before 2010 than in more recent studies. The study authors recognise this as an indication of the increasing clarithromycin resistance in H. pylori.

1. Sugano K, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015; 64: 1353-1367.
2. Liou JM, et al. Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus. Gut 2020; 69: 2093-2112.
3. Graham DY. Transitioning of Helicobacter pylori therapy from trial and error to antimicrobial stewardship. Antibiotics 2020; 9: 671
4. Rokkas T, et al. Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: a Network Meta-Analysis. Gastroenterology 2021.
5. El-Serag HB, et al. Houston Consensus Conference on testing for Helicobacter pylori infection in the United States. Clin Gastroenterol Hepatol 2018; 16: 992-1002.