Standard treatments for H pylori include clarithromycin, metronidazole, or amoxicillin in conjunction with gastric acid inhibitors. The prevalence of resistance to clarithromycin and metronidazole has increased substantially in recent years, and a corresponding decrease in the eradication rate for H pylori infection in most Western countries has occurred. Sequential therapy, a new regimen administering antimicrobials in a given sequence rather than all simultaneously, has generated much interest. It involves a simple dual therapy including a proton pump inhibitor (PPI) plus amoxicillin 1g (both twice daily) given for the first five days, followed by a triple therapy including a PPI, clarithromycin 500 mg, and a nitroimidazole antimicrobial (all twice daily) for the remaining five days. Initial studies suggest that its superiority over standard triple therapy might be due to improved eradication of clarithromycin resistant strains.
In the BMJ, researchers present the findings of their meta-analysis to assess the efficacy of sequential therapy compared with other eradication regimens. They assessed 46 RCTs [n= 5666 sequential therapy and 7866 to other (established and new) treatments].
The overall eradication rate of sequential therapy was 84.3% (95% CI, 82.1% to 86.4%). Sequential therapy was superior to seven day triple therapy (relative risk 1.21, 95% CI, 1.17 to 1.25; I2=29.3%; NNT 6 , 95% CI, 5 to 7), marginally superior to 10 day triple therapy (1.11, 1.04 to 1.19; I2= 67.2%; NNT 10, 7 to 15), but not superior to 14 day triple therapy (1.00, 0.94 to 1.06; I2=54.3%), bismuth based therapy (1.01, 0.95 to 1.06; I2=21.1%), and non-bismuth based therapy (0.99, 0.94 to 1.05; I2=52.3%). Data on eradication according to pre-treatment antimicrobial susceptibility testing were available in eight studies, and sequential therapy was able to eradicate 72.8% (61.6% to 82.8%) of the strains resistant to clarithromycin.
The researchers acknowledge that as with any systematic review and meta-analysis, limitations of such research include reliance on the quality and reporting of the trials. In their analysis, most of the studies had methodological problems with concealment of allocation and blinding and there was significant heterogeneity. They add that the applicability of the results should also be viewed with caution, as information on efficacy of sequential therapy in several Western countries is lacking: no studies have been reported from Canada, and few southern European countries are represented. Also data on the response of treatments according to pre-treatment sensitivity was available in a minority of the overall patients studied, not allowing a thorough analysis of the results. They stress that the need for a new agent to treat H pylori is important, and until such an agent is discovered, any single therapy is unlikely to be effective globally.