Failures in a proton pump inhibitor therapeutic substitution program: lessons learned

Area of Science:

• Gastroenterology
• Pharmacology
• Patient Outcomes

Background:

• Patient dissatisfaction with involuntary therapeutic substitutions of proton pump inhibitors (PPIs) is not well understood.
• Understanding factors contributing to treatment failure is crucial for optimizing gastroesophageal reflux disease (GERD) management.

Purpose of the Study:

• To characterize patients experiencing therapeutic failure in a lansoprazole-rabeprazole substitution program.
• To investigate if individual response differences contribute to PPI therapeutic failure.

Main Methods:

• Comparison of treatment failures versus successes in a lansoprazole-rabeprazole substitution program.
• A randomized, double-blind, double-dummy, crossover study in a subgroup of patients.
• Assessment of gastroesophageal reflux disease (GERD) symptoms using the GERD Symptom Assessment Scale.

Main Results:

• Nonresponders (115) were more likely to have a GERD diagnosis (74%) and prior upper endoscopy (50%) compared to responders (54).
• A majority of PPI nonresponders had a clinical GERD diagnosis and were on high-dose rabeprazole (>/=40 mg daily).
• Responder status showed higher reliability for lansoprazole (kappa=0.80) than rabeprazole (kappa=0.21).

Conclusions:

• Patients with GERD and those who have undergone upper endoscopy are more prone to therapeutic failure with PPI substitutions.
• High-dose rabeprazole may be associated with nonresponse in certain patient populations.
• Further research is needed to understand nonresponse patterns in PPI therapeutic substitution programs.