Abstract
Rising antibiotic resistance has challenged empirical regimens for Helicobacter pylori eradication. While concomitant therapy is widely used, its effectiveness is reduced in resistant settings. Tailored therapy, guided by antimicrobial susceptibility testing, may improve outcomes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing tailored versus concomitant therapy as a first-line treatment. We searched PubMed, Google Scholar, Cochrane, and ClinicalTrials.gov through April 2025 for RCTs enrolling treatment-naïve adults with confirmed H. pylori infection. The primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses, with adverse events as a secondary outcome. We included eight RCTs with 2524 patients (1332 tailored, 1192 concomitant). Tailored therapy achieved higher eradication rates than concomitant therapy in the ITT analysis (87.4% vs. 83.2%; RR = 1.05; 95% CI: 1.00-1.10; p = 0.05) and the PP analysis (92.6% vs. 89.1%; RR = 1.04; 95% CI: 1.00-1.07; p = 0.03). Furthermore, tailored therapy was associated with a significantly lower incidence of adverse events (35.6% vs. 45.6%; RR = 0.71; 95% CI: 0.58-0.86; p = 0.0007). In conclusion, tailored therapy provides modestly higher H. pylori eradication rates and significantly fewer adverse events compared to empirical concomitant therapy. These findings support using tailored therapy as the preferred first-line option, particularly in regions with high antibiotic resistance and as access to rapid molecular testing expands.