Failures in a Proton Pump Inhibitor Therapeutic Substitution Program: Lessons Learned (original) (raw)

Abstract

The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy (50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater κ coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving ≥40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs.

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Acknowledgments

This was an investigator-initiated study supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service Grant DK56338, which funds the Texas Gulf Coast Digestive Diseases Center. Small amounts of funds were made available to support the IRB costs and drugs and matching placebos were supplied by PriCara, Unit of Ortho-McNeil, Inc., and Eisai Inc. and TAP. None of the authors who were not employees of TAP were paid consultants for TAP or other makers of proton pump inhibitors.

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Authors and Affiliations

  1. VA Medical Center, Houston, TX, USA
    Maggie Lu & David Y. Graham
  2. Baylor College of Medicine, Houston, TX, USA
    Vikram Malladi, Aamer Agha, Suhaib Abudayyeh & David Y. Graham
  3. TAP Pharmaceutical Products Inc., Lake Forest, IL, USA
    Cong Han & Nancy Siepman
  4. Michael E. DeBakey Veterans Affairs Medical Center, Room 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX, 77030, USA
    David Y. Graham

Authors

  1. Maggie Lu
  2. Vikram Malladi
  3. Aamer Agha
  4. Suhaib Abudayyeh
  5. Cong Han
  6. Nancy Siepman
  7. David Y. Graham

Corresponding author

Correspondence toDavid Y. Graham.

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Lu, M., Malladi, V., Agha, A. et al. Failures in a Proton Pump Inhibitor Therapeutic Substitution Program: Lessons Learned.Dig Dis Sci 52, 2813–2820 (2007). https://doi.org/10.1007/s10620-007-9811-7

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