What is the comparison of Vonaprazon, Fexuprazon, and Tegaprazon in terms of efficacy and safety for treating gastroesophageal reflux disease (GERD)?

Comparison of Vonaprazon, Fexuprazan, and Tegaprazan for GERD Treatment

Direct Answer

Among the three P-CABs, vonoprazan has the strongest evidence base and regulatory approval for GERD treatment, while fexuprazan and tegaprazan have limited data and should not be used as first-line therapy. 1, 2

Evidence Quality and Availability

Vonoprazan

• Vonoprazan is the only P-CAB with extensive clinical trial data, FDA approval in the United States, and guideline-based recommendations for GERD management. 1, 3
• The American Gastroenterological Association has issued specific positioning statements for vonoprazan, recommending it after failure of twice-daily PPI therapy rather than as first-line treatment. 1
• Clinical trials demonstrate non-inferiority to lansoprazole for healing erosive esophagitis (94% vs 91% for LA grade A/B) and superiority for maintenance of healing in severe erosive esophagitis (75-77% vs 62% for LA grade C/D). 1, 4

Fexuprazan

• Fexuprazan has minimal published clinical data and should generally not be used as first-line therapy where clinical superiority over PPIs has not been demonstrated. 2
• Pharmacodynamic studies show fexuprazan 40 mg provides acid inhibition similar to standard PPI doses rather than more potent suppression, limiting its theoretical advantage. 2
• Like vonoprazan, fexuprazan is not metabolized by CYP2C19, eliminating genetic polymorphism variability. 2

Tegaprazan

• Tegaprazan is only marketed in Latin American countries with extremely limited published evidence for GERD treatment. 5
• No specific guideline recommendations or comparative efficacy data are available in the provided evidence. 5

Clinical Positioning Algorithm

Step 1: Initial GERD Management

• Start with standard-dose PPI therapy for all patients with GERD, regardless of severity. 1
• Reserve P-CABs for patients who fail standard therapy due to cost considerations and lack of demonstrated first-line superiority. 1, 2

Step 2: PPI Treatment Failure

• Escalate to twice-daily PPI therapy if inadequate response to standard dosing. 1
• Document treatment failure with objective measures (pH monitoring showing inadequate acid suppression) when possible. 1

Step 3: P-CAB Selection After PPI Failure

• Consider vonoprazan 20 mg daily only after documented failure of twice-daily PPI therapy. 1
• Vonoprazan is particularly effective for severe erosive esophagitis (LA grade C/D), with significantly lower recurrence rates (5-13% vs 39% for lansoprazole). 1
• Do not use fexuprazan or tegaprazan given the lack of robust comparative data and guideline support. 2, 5

Step 4: Maintenance Therapy

• For mild erosive esophagitis (LA grade A/B): Vonoprazan 10 mg daily achieves maintenance rates of 81-82% vs 77% for lansoprazole. 1
• For severe erosive esophagitis (LA grade C/D): Vonoprazan demonstrates clear superiority with maintenance rates of 75-77% vs 62% for lansoprazole. 1

Efficacy Comparison by GERD Subtype

Non-Erosive Reflux Disease (NERD)

• Vonoprazan shows inconsistent results in NERD, with minimal difference from placebo in some trials. 1
• The American Gastroenterological Association does not recommend vonoprazan as first-line therapy for NERD. 1
• No data available for fexuprazan or tegaprazan in NERD. 2, 5

Mild Erosive Esophagitis (LA Grade A/B)

• Vonoprazan has similar healing efficacy to PPIs (94% vs 91%), making it difficult to justify the higher cost for first-line use. 1
• Maintenance benefits are modest (81-82% vs 77%), not warranting routine use over PPIs. 1

Severe Erosive Esophagitis (LA Grade C/D)

• This is where vonoprazan demonstrates clear clinical superiority, with healing rates of 75-77% vs 62% for lansoprazole and dramatically lower recurrence rates. 1, 4
• Consider vonoprazan earlier in the treatment algorithm for patients with documented LA grade C/D esophagitis who fail standard PPI therapy. 1

Safety Considerations

Short-Term Safety

• Vonoprazan has comparable short-term safety to PPIs, with common adverse events including abdominal pain, constipation, diarrhea, nausea, and dyspepsia. 3
• Fexuprazan appears to have similar safety to PPIs, with comparable risks of enteric infections. 2

Long-Term Safety Concerns

• Long-term safety data for all P-CABs are more limited than for PPIs, which is a significant consideration for chronic GERD management. 1
• More pronounced hypergastrinemia occurs with vonoprazan compared to PPIs due to more potent acid suppression. 6
• The clinical significance of elevated gastrin levels with long-term P-CAB use remains uncertain. 6

Critical Cost Considerations

• Vonoprazan is significantly more expensive than both standard-dose and double-dose PPIs in the United States, which substantially limits its use as first-line therapy. 1
• Cost-effectiveness has not been established for fexuprazan or tegaprazan, and they should not be prescribed when standard PPIs would be more cost-effective. 2
• The substantial cost differential requires demonstration of clear clinical superiority before selecting any P-CAB over twice-daily PPI therapy. 1, 2

Common Pitfalls to Avoid

• Do not prescribe vonoprazan, fexuprazan, or tegaprazan as first-line therapy for mild GERD or NERD when PPIs would be equally effective and far more cost-effective. 1, 2
• Avoid assuming that more potent acid inhibition automatically translates to superior clinical outcomes across all GERD presentations. 2
• Do not overlook the need for objective documentation of PPI failure (such as pH monitoring) before escalating to expensive P-CAB therapy. 1
• Avoid prescribing fexuprazan or tegaprazan given the absence of robust clinical data and guideline support compared to vonoprazan. 2, 5

Special Clinical Scenarios

PPI-Refractory GERD

• Vonoprazan provides more potent gastric acid suppression in patients with documented PPI-refractory GERD, achieving normalization of esophageal acid exposure in 46% of patients who failed PPI therapy. 7
• Complete gastric acid suppression with vonoprazan is associated with successful normalization of esophageal acid exposure. 7

H. pylori Eradication

• Vonoprazan provides 10-20% higher eradication rates in clarithromycin-based triple therapy, with superiority confined to clarithromycin-resistant strains. 1
• Dual therapy with vonoprazan and amoxicillin achieves eradication rates approaching 95% for first-line treatment. 1
• Tegoprazan has been investigated for H. pylori eradication, but specific comparative data are not provided in the available evidence. 5