Vonoprazan–Doxycycline Dual Therapy Matches Amoxicillin Regimen for H. pylori Eradication
核心洞察
A retrospective cohort study of 357 patients found vonoprazan–doxycycline dual therapy achieved H. pylori eradication rates comparable to vonoprazan–amoxicillin (ITT 76.1% vs 78.0%; PP 87.3% vs 89.0%).
No statistically significant difference in eradication was observed between the two regimens in either ITT or PP analysis (P = 0.677 and P = 0.629, respectively).
The doxycycline regimen showed a higher overall adverse event rate (19.7% vs 11.0%), driven mainly by nausea/vomiting and decreased appetite, though all events were mild to moderate.
A retrospective cohort study conducted across three centers in the Ningxia region of northwestern China found that vonoprazan–doxycycline dual therapy achieved Helicobacter pylori (搜索) eradication outcomes broadly comparable to vonoprazan–amoxicillin high-dose dual therapy as first-line treatment. The findings, published in Infection and Drug Resistance, suggest a simplified, penicillin-free regimen may offer a viable alternative for patients with penicillin allergy or those requiring treatment simplification.
Study Design and Patient Population
The study enrolled 357 patients for intention-to-treat (ITT) analysis—180 in the doxycycline dual-therapy group and 177 in the amoxicillin dual-therapy group—between December 2024 and December 2025. Of these, 157 patients in the doxycycline group and 155 in the amoxicillin group completed the full treatment course and follow-up, forming the per-protocol (PP) analysis population.
Both regimens were administered for 14 days. The vonoprazan–doxycycline group received vonoprazan 20 mg twice daily (30 minutes before meals) plus doxycycline 100 mg twice daily (30 minutes after meals). The vonoprazan–amoxicillin group received vonoprazan 20 mg twice daily plus amoxicillin 1000 mg three times daily. No statistically significant differences were observed between groups in baseline characteristics, including age, body mass index, sex, smoking history, alcohol consumption, family history of gastric cancer, and consumption of pickled foods (all P > 0.05).
Eradication Efficacy
In the ITT analysis, H. pylori eradication rates were 76.1% (137/180) in the doxycycline group and 78.0% (138/177) in the amoxicillin group, with a risk difference of −1.9% (95% CI: −10.6% to 6.9%) and no statistically significant difference (χ² = 0.17, P = 0.677). In the PP analysis, eradication rates were 87.3% (137/157) and 89.0% (138/155), respectively, with a risk difference of −1.8% (95% CI: −8.9% to 5.4%) and again no significant difference (χ² = 0.23, P = 0.629).
After multivariable logistic regression adjusting for age, BMI, sex, smoking, alcohol consumption, family history of gastric cancer, and pickled-food consumption, the doxycycline group showed no statistically significant difference in eradication success compared with the amoxicillin group in the ITT analysis (adjusted OR = 0.88, 95% CI 0.53–1.46, P = 0.626).
The authors noted that the ITT eradication rates of 76.1% and 78.0% fell short of the 80% threshold recommended by domestic and international guidelines for first-line regimens. They attributed this shortfall to a conservative analytical approach—classifying patients with incomplete records or unavailable follow-up as treatment failures—and to the retrospective design's limited oversight of patient adherence.
Safety Profile
PP analysis revealed that at least one adverse event occurred in 31 patients (19.7%) in the doxycycline group and 17 patients (11.0%) in the amoxicillin group, a statistically significant difference (P ≤ 0.05). The incidence of nausea/vomiting and decreased appetite was significantly higher in the doxycycline group (both P ≤ 0.05), while no significant differences were observed in abdominal bloating, abdominal pain, headache/dizziness, acid reflux, or dry/bitter mouth. All adverse events were mild to moderate in severity; no patient discontinued treatment, and all symptoms resolved or improved spontaneously following completion of therapy.
The authors observed that the overall adverse event rate of 19.7% in the doxycycline group was lower than the 39.8% reported in a prior randomized controlled trial of vonoprazan combined with bismuth, doxycycline, and metronidazole, suggesting the simplified dual regimen may reduce adverse event burden through a reduction in total medication count.
Clinical Rationale
Doxycycline, a second-generation semi-synthetic tetracycline, exhibits antibacterial activity 2–4 times greater than tetracycline and favorable pharmacokinetic properties, including high lipophilicity, superior tissue penetration, and a prolonged half-life of 12–22 hours. Vonoprazan, a potassium-competitive acid blocker, exerts rapid, potent, and sustained acid suppression independently of CYP2C19 genetic polymorphisms. The authors cautioned, however, that no in vitro or in vivo experiments were conducted to demonstrate true synergistic interaction between the two agents, and the proposed complementarity remains a hypothesis requiring confirmation.
The study's authors emphasized that approximately 5–10% of patients with H. pylori infection have documented penicillin allergy, precluding amoxicillin-based regimens, and that the primary resistance rate of H. pylori to tetracycline in China has been reported at 2.53%—substantially lower than rates for clarithromycin (30.72%), metronidazole (70.14%), and levofloxacin (32.98%).
Limitations
The authors acknowledged several limitations, including the non-randomized retrospective design with potential residual confounding, the absence of antibiotic susceptibility testing, and the study's restriction to the Ningxia region of northwestern China. They called for future prospective, multicenter, large-scale randomized controlled trials incorporating antibiotic susceptibility testing and formal non-inferiority designs to validate the efficacy and safety of vonoprazan–doxycycline dual therapy.