What is the effectiveness of vonoprazan in maintaining Gastroesophageal Reflux Disease (GERD) compared to other Proton Pump Inhibitors (PPIs)?

Effectiveness of Vonoprazan in Maintaining GERD Compared to Other PPIs

Vonoprazan should generally not be used as first-line therapy for GERD maintenance but may be superior to PPIs specifically for severe erosive esophagitis (LA grade C/D) maintenance with healing rates of 75-77% versus 62% for lansoprazole. 1

Mechanism and Pharmacodynamics

• Vonoprazan is a potassium-competitive acid blocker (P-CAB) that suppresses gastric acid secretion by inhibiting the H+, K+-ATPase enzyme system in a potassium-competitive manner 2
• Unlike PPIs, vonoprazan does not require activation by acid and binds to proton pumps in a noncovalent and reversible manner 2
• Following a single 20 mg dose, vonoprazan achieves rapid onset of antisecretory effect within 2-3 hours and maintains elevated intragastric pH for over 24 hours 2
• By day 7 of treatment with vonoprazan 20 mg daily, mean intragastric pH increases to 5.9 and the percentage of time with pH>4 reaches 85.2% (20 hours/day), which is more potent than typical PPI acid suppression 2

Effectiveness in Different GERD Subtypes

Non-Erosive Reflux Disease (NERD)

• Vonoprazan is not recommended as first-line therapy for NERD according to AGA guidelines 1, 3
• Clinical trials from Japan show inconsistent results with one study finding minimal difference between vonoprazan and placebo (10-12% vs 7% heartburn-free days), while another showed a trend toward improvement (72% vs 62% heartburn-free days; p=0.06) 1
• For PPI-resistant NERD, vonoprazan demonstrated moderate efficacy with improvement in FSSG scores in 74.6% of patients at 4 weeks 4

Mild Erosive Esophagitis (LA Grade A/B)

• For LA grade A/B erosive esophagitis, vonoprazan has similar healing efficacy to PPIs (94% vs 91% for lansoprazole) 1
• Maintenance of healing rates at 24 weeks for LA grade A/B EE are slightly better with vonoprazan compared to lansoprazole (81-82% vs 77%) 1
• Despite these modest benefits, AGA guidelines recommend against using vonoprazan as first-line therapy for milder EE due to higher costs and limited availability 1, 3

Severe Erosive Esophagitis (LA Grade C/D)

• Vonoprazan shows superior efficacy for maintenance of healing in severe EE (LA grade C/D) compared to lansoprazole (75-77% vs 62%) 1
• A Japanese randomized trial showed significantly lower recurrence rates with vonoprazan 10-20 mg than lansoprazole 15 mg in LA grade C/D EE (5-13% vs 39%) 1
• Meta-analyses confirm that vonoprazan is more effective than PPIs specifically for patients with severe erosive esophagitis 5, 6

PPI-Resistant GERD

• For PPI-resistant erosive esophagitis, vonoprazan 20 mg achieves high healing rates of 91.7% at 4 weeks and 88.5% at 8 weeks 4
• Maintenance rates for healed PPI-resistant EE with vonoprazan 10 mg are 82.6% at 8 weeks, 86.0% at 24 weeks, and 93.8% at 48 weeks 4
• A small retrospective study found that vonoprazan 10 mg daily improved symptoms in 88% of patients with PPI-resistant GERD, with higher resolution rates in erosive (83%) versus non-erosive disease (28%) 7

Comparative Efficacy vs. PPIs

• A network meta-analysis comparing vonoprazan 10 mg to PPIs for GERD maintenance showed odds ratios of 13.92 vs esomeprazole 10 mg, 5.75 vs rabeprazole 10 mg, 3.74 vs lansoprazole 15 mg, and 9.23 vs omeprazole 10 mg 8
• For healing of GERD at 8 weeks, vonoprazan 20 mg showed odds ratios of 2.29 vs esomeprazole 20 mg, 3.94 vs rabeprazole 20 mg, 2.40 vs lansoprazole 30 mg, and 2.71 vs omeprazole 20 mg 6
• A systematic review and meta-analysis found vonoprazan to be non-inferior to PPIs for GERD therapy overall, with an RR of 1.06 (0.99-1.13) 5

Clinical Considerations and Limitations

• The AGA recommends against using vonoprazan as first-line therapy for acid-related conditions where clinical superiority has not been clearly demonstrated 1
• Cost considerations are significant, as vonoprazan is markedly more expensive than both standard and double-dose PPIs in the United States 1, 3
• Long-term safety data for vonoprazan are more limited than for PPIs, though short-term safety appears comparable with similar adverse event profiles (RR 1.08,0.96-1.22) 1, 5
• Vonoprazan causes elevated serum gastrin levels that remain elevated during treatment and return to normal within 4 weeks of discontinuation 2

Algorithm for Vonoprazan Use in GERD Maintenance

1. For initial GERD treatment, start with standard PPI therapy 3
2. If inadequate response, escalate to twice-daily PPI therapy 1, 3
3. For patients with documented acid-related reflux who fail twice-daily PPI therapy:
   • For NERD or LA grade A/B EE: Consider vonoprazan 10-20 mg daily 1, 3
   • For LA grade C/D EE: Consider vonoprazan 10-20 mg daily as it shows superior maintenance of healing 1
4. For PPI-resistant GERD with confirmed erosions: Vonoprazan 20 mg daily for healing, followed by 10 mg daily for maintenance 7, 4

Common Pitfalls to Avoid

• Using vonoprazan as first-line therapy for mild GERD when PPIs would be more cost-effective 1, 3
• Failing to consider the higher cost of vonoprazan compared to PPIs when making treatment decisions 1, 3
• Not confirming acid-related pathology before escalating to vonoprazan in patients with refractory symptoms 1
• Overlooking the potential for elevated gastrin levels and enterochromaffin-like cell hyperplasia with long-term vonoprazan use 2