Understanding and appreciating sequential therapy for Helicobacter pylori eradication

Abstract

Despite the fact that sequential therapy has been evaluated in more than 2500 patients and has been shown to on average provide Helicobacter pylori eradication in 90% to 94%, some authorities still question whether it should be a first-line anti-H. pylori regimen. Here, we discuss H. pylori eradication using experience and expectations with other common bacterial infections as a frame of reference. H. pylori is no exception and near 100% success is expected for optimized regimens treating susceptible infections. As such, the proper comparator would be the relation to 100% eradication. Superiority to another, often proven inferior, therapy per se provides little or no useful information. Treatment failures in infectious diseases are typically easily explainable and most often relate to the presence of antimicrobial resistance or failure to take the drugs. We provide a model for predicting the results of H. pylori combination therapies in relation to the pattern and prevalence of resistance. The results are consistent with clinical practice and explain why sequential is typically superior and essentially never inferior to triple therapy. We also show when meta-analysis is an inappropriate technique for the analysis of H. pylori clinical trials and discuss how to appropriately use the technique. Finally, we discuss why the location of studies (eg, Italy), is unimportant and explain why, from the standpoint of a therapy for an infectious disease, sequential therapy is a significant advance and should be considered one of the replacements for the outdated legacy triple therapy (proton pump inhibitor--clarithromycin--amoxicillin).

Figure 1. Results of a theoretical clinical trial evaluating different clarithromycin-containing H. pylori eradication regimens

Scenario: 100 patients per group from a population with a susceptibility pattern of 20% clarithromycin resistant, 20% metronidazole resistant and 0% amoxicillin resistant. Therefore among each 100 subjects 64 would be susceptible to all agents, 16 each would be clarithromycin resistant, 16 would be metronidazole resistant and 4 would be resistant to both clarithromycin and metronidazole (dual resistance). Treatment success is also graded using the Report Card scoring system .