Molecular Testing-Guided Therapy a Viable Option for Helicobacter pylori Eradication

Molecular testing-guided therapy was similar to susceptibility testing-guided therapy as first-line treatment for Helicobacter pylori (H pylori) infection and not inferior to susceptibility testing-guided therapy as third-line treatment, according to study results published in The Lancet Gastroenterology & Hepatology.

Researchers conducted 2 multicenter, open-label, randomized controlled trials (ClinicalTrials.gov Identifier: NCT03556254; NCT03555526) to compare the efficacy and safety of molecular testing-guided therapy and traditional culture-based susceptibility testing-guided therapy in first-line (trial 1) and third-line (trial 2) treatment of H pylori infection among patients.

Trial 1 included treatment-naive individuals infected with H pylori who were aged at least 20 years, and trial 2 enrolled patients aged at least 20 years who failed treatment after 2 or more eradication therapies for H pylori infection.

Study participants were randomly assigned 1:1 to receive molecular testing-guided therapy or susceptibility testing-guided therapy. They received clarithromycin sequential therapy, levofloxacin sequential therapy, or bismuth quadruple therapy according to molecular testing or traditional susceptibility testing for resistance to clarithromycin and levofloxacin.

The primary outcome was eradication rate in the intention-to-treat analysis.

For trial 1, 560 treatment-naive patients with H pylori infection were randomly assigned from March 28, 2018 to April 23, 2021. In trial 2, 320 patients with refractory H pylori infection were randomly assigned from December 28, 2017 to October 27, 2020.

Trial 1 participants had a mean [SD] age of 50.9[12.9] years in the molecular testing-guided therapy group and 53.4[13.6] years in the susceptibility testing-guided therapy group. For trial 2, participants’ mean age was 54.1[11.4] years in the molecular testing-guided therapy group and 53.4[10.9] years in the susceptibility testing-guided therapy group. A total of 272 men and 288 women were recruited in trial 1, and 98 men and 222 women were enrolled in trial 2.

As first-line H pylori treatment in trial 1, infection was eradicated in 241 (86%; 95% CI, 82-90) of 280 patients in the molecular testing-guided therapy group and 243 (87%; 95% CI, 83-91) of 280 patients in the susceptibility testing-guided therapy group in the intention-to-treat analysis (P = .81).

In trial 2 as third-line treatment, H pylori infection was eradicated in 141 (88%; 95% CI, 83-93) of 160 patients in the molecular testing-guided therapy group and 139 (87%; 95% CI, 82-92) of 160 patients in the susceptibility testing-guided therapy group in the intention-to-treat analysis (P = .74).

With use of the noninferiority margin of 5% from trial 1, the difference in eradication rate between the molecular testing-guided therapy group and the susceptibility testing-guided therapy group was -0.7% (95% CI, -6.4 to 5.0; noninferiority P = .071) in the intention-to-treat analysis and -1.0% (95% CI, -5.9 to 3.8; noninferiority P = .059) in the per-protocol analysis.

Based on the prespecified noninferiority margin of 10% in trial 2, the difference in eradication rate between the molecular testing-guided therapy group and the susceptibility testing-guided therapy group was 1.3% (-6.0 to 8.5; noninferiority P = .0018) in the intention-to-treat analysis and 1.2% (-5.5 to 8.0; noninferiority P = .0012) in the per-protocol analysis. As third-line treatment, efficacy in the molecular testing-guided therapy group was not inferior to that observed in the susceptibility testing-guided therapy group.

No significant differences occurred in the frequency of adverse effects between the 2 groups in trials 1 and trial 2. In addition, no significant differences in eradication rates were found between men (P = .83 in trial 1 and .96 in trial 2) and women (P = .55 in trial 1 and .65 in trial 2).

Study limitations include the fact that first-line therapy did not meet the anticipated high eradication rate and that the COVID-19 pandemic resulted in a high dropout rate for treatment-naive patients. Also, the therapy was not guided by susceptibility testing for amoxicillin and tetracycline, owing to low primary resistance rates, and gastric biopsy specimens were used for molecular testing.

“Our results support the use of molecular testing–guided therapy for H pylori infection in clinical practice,” the study authors wrote. “Whether susceptibility testing–guided therapy is superior to empirical therapy, particularly in third-line treatment, remains controversial and warrants further, large-scale, randomized trials.”

This article originally appeared on Gastroenterology Advisor