New meta-analysis of H. pylori treatments ranks standard therapy last

Last Updated: 2015-09-04

By Joan Stephenson

NEW YORK (Reuters Health) - The previously recommended seven days of standard triple treatment for Helicobacter pylori infection was ranked the least effective of 14 newer or well-established regimens in a new systematic review and network meta-analysis by researchers in China.

A comparison of the regimens, online August 19 in the BMJ, identified a half-dozen (including standard triple therapy supplemented with probiotics) that might be better alternatives.

The researchers decided to conduct the review and meta-analysis because the most effective and tolerable of the many treatment regimens that have been developed to treat H. pylori infection is unknown, they note in their report.

"Treatment of this widespread infection remains an ongoing challenge, given the estimated rates of infection in the population and the growing resistance of bacteria to antibiotics," corresponding author Dr. Dong-Qing Ye, of Anhui Medical University in Hefei, told Reuters Health by email.

Previous meta-analyses of H. pylori therapies used conventional methods, which means limiting the analysis to treatments directly compared in clinical trials, Dr. Ye said. The network meta-analysis used in the current study permits "both direct and indirect comparisons across treatments, provided that a common comparator exists," the authors explained.

The researchers searched the literature for reports of randomized trials that compared different treatments for H. pylori. They found 143 that met their inclusion criteria, which included eradication assessments at least four weeks after the end of treatment and an intention-to-treat analysis.

More than 32,000 patients contributed to the efficacy analysis and more than 22,000 to the analysis of tolerance. Average age of participants was 47 years; 53% were men.

Data on 14 well-established or newer treatment regimens were available for analysis. Of these, six performed significantly better compared with standard triple therapy (seven days of simultaneous treatment with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole), which was assigned a risk ratio of 1):

1. Seven days of "concomitant treatment," that is, simultaneous treatment with a PPI and three kinds of antibiotics (RR = 1.29; eradication rate, 0.94).

2. 10 or 14 days of concomitant treatment (RR = 1.24; eradication rate, 0.91).

3. 10 or 14 days of standard triple treatment supplemented with probiotics (RR = 1.24; eradication rate, 0.90).

4. 10 or 14 days of levofloxacin-based triple treatment (simultaneous PPI, levofloxacin, and another antibiotic) (RR = 1.23; eradication rate, 0.90).

5. 14 days of hybrid treatment (simultaneous PPI and amoxicillin for seven days, followed by simultaneous PPI, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days) (RR = 1.22; eradication rate, 0.89)

6. 10 or 14 days of sequential treatment (five or seven days of simultaneous PPI plus amoxicillin, followed by five or seven additional days of simultaneous PPI plus clarithromycin and 5-nitroimidazole or amoxicillin) (RR = 1.20; eradication rate, 0.87)

In most cases, longer treatments were more effective, but less tolerable.

"Prolonging treatment, unsurprisingly, seemed to increase the risk of adverse events," Dr. Ye said.

Seven days of probiotic-supplemented triple treatment and seven days of levofloxacin-based triple treatment ranked best among the 14 regimens in terms of tolerance, although all of the treatment regimens were considered tolerable.

However, the results on tolerance of treatments "should be interpreted with caution because most network meta-analysis comparisons did not reach statistical significance," the authors said.

The authors also noted that "one single 'most effective' treatment is unlikely to be identified across the world, as the treatments will need to be tailored to regional resistance profiles."

Treatment regimens to eradicate H. pylori "are not straightforward," Dr. Sheila E. Crowe, vice president of the American Gastroenterology Association and a professor of medicine at the University of California, San Diego, told Reuters Health in an email.

Rising resistance rates to certain antibiotics in the most commonly used treatment regimens and noncompliance and side effects related to the multiple components typically found in regimens "lead to treatments that are not very effective," she said.

"The approach and data presentation used in this publication are novel, with the 'Network of eligible comparisons' figures likely to brighten lectures on the topic of (H. pylori therapy) for some time to come," Dr. Crowe said. "On the strength of this article, I may start recommending probiotics when I do choose triple treatment."

The study had no commercial funding, and the authors reported no disclosures.

SOURCE: http://bit.ly/1UpcGiJ

BMJ 2015