In a 28‑year‑old woman with 5 days of epigastric pain, severe antral gastritis on endoscopy, a negative rapid urease test, and no symptom relief with standard‑dose proton‑pump inhibitor plus sucralfate, what is the role of increasing the proton‑pump inhibitor to twice‑daily dosing versus using vonoprazan?

Increase PPI to Twice Daily Rather Than Switch to Vonoprazan

In this 28-year-old woman with H. pylori-negative severe antral gastritis not responding to standard-dose PPI plus sucralfate, you should increase the PPI to twice-daily dosing before considering vonoprazan. The current evidence does not support vonoprazan as first-line therapy for peptic ulcer disease or non-H. pylori gastritis 1.

Rationale for PPI Dose Escalation First

The 2024 AGA guidelines explicitly state that clinicians should generally not use P-CABs (vonoprazan) as first-line therapy in the treatment or prophylaxis of peptic ulcer disease 1. This recommendation applies to your patient's severe antral gastritis, which falls under the broader category of acid-related mucosal injury.

Why Double-Dose PPI is the Appropriate Next Step:

• Standard escalation pathway: When standard-dose PPI fails, doubling the dose is the established next step, with approximately 20-25% of PPI-refractory patients responding to dose escalation 2
• Cost-effectiveness: Vonoprazan is markedly more expensive than generic PPIs, and the guidelines note that benefits do not justify routine first-line use 1
• Equivalent efficacy for ulcer healing: A 2024 meta-analysis found that healing rates of gastric and/or duodenal ulcers were similar between vonoprazan and PPIs at all time points (Week 2,4,6, and 8), with no significant difference 3

When Vonoprazan Would Be Indicated

Vonoprazan has specific, evidence-based indications where it outperforms PPIs:

1. H. pylori eradication (not applicable here—RUT negative) 1, 4
2. Severe erosive esophagitis (LA grade C/D) (not your patient's presentation) 1
3. Maintenance of healed severe esophagitis 1

Practical Management Algorithm

Immediate Steps:

1. Optimize current PPI therapy:

   • Ensure proper timing: 30-60 minutes before breakfast
   • Verify compliance
   • Consider switching PPI class if on same agent (e.g., omeprazole to esomeprazole or pantoprazole)

2. Escalate to twice-daily PPI:

   • Standard dose 30-60 minutes before breakfast AND dinner
   • Continue for 8 weeks minimum
   • Maintain sucralfate if tolerated

3. Re-evaluate H. pylori status:

   • RUT can have false negatives
   • Consider stool antigen or urea breath test if not already done
   • Histology from biopsy specimens if available

Important Caveats:

• Hypergastrinemia risk: If you eventually use vonoprazan, be aware it causes more marked hypergastrinemia than PPIs, especially in patients without atrophic gastritis 5—relevant for your young patient with severe antral gastritis

• Diagnostic considerations: Severe antral gastritis in a young H. pylori-negative patient warrants consideration of:

  • Bile reflux gastritis
  • NSAID use (even if denied)
  • Autoimmune gastritis (though typically corpus-predominant)
  • Rare entities like collagenous gastritis 6

If Double-Dose PPI Fails After 8 Weeks:

Only then consider vonoprazan as second-line therapy, recognizing that:

• It provides more potent acid suppression 4
• The higher cost may be justified after PPI failure
• Monitor for hypergastrinemia with long-term use 5

The evidence clearly supports PPI dose optimization before vonoprazan in this clinical scenario, reserving vonoprazan for true PPI-refractory cases or its specific approved indications.