This systematic review was produced by the Drug Assessment Working Group of the Therapeutics Initiative at the request of the Pharmaceutical Services Division (PSD) of the British Columbia Ministry of Health as part of the Drug Effectiveness Review Project (DERP), a class review of proton pump inhibitors (PPIs) for the treatment of adult patients with symptomatic GERD or PUD.
Four research questions were investigated:
- Based on head to head randomized controlled trials, does Esomeprazole or Lansoprazole provide a therapeutic advantage (includes benefit and harm) as compared to other proton pump inhibitors (Omeprazole, Pantoprazole or Rabeprazole) in adult patients with symptomatic GERD?
- Based on head to head randomized controlled trials, does Esomeprazole or Lansoprazole provide a therapeutic advantage (includes benefit and harm) as compared to other proton pump inhibitors (Omeprazole, Pantoprazole or Rabeprazole) in adult patients with symptomatic PUD?
- Based on head to head randomized controlled trials, are there subgroups of patients based on demographics, other medications or co-morbidities (including nasogastric tubes and inability to swallow solid oral medication) for which a particular proton pump inhibitor or preparation is more effective or associated with fewer adverse effects in adult patients with symptomatic GERD and PUD?
- Based on large, long term (6 months or more), select comparative observational studies (cohort and nested case control) what is the safety and adverse events profile of different proton pump inhibitors in adult patients with symptomatic GERD and PUD?
Due to the paucity of high-quality data, the results presented in this review provide weak/poor evidence of the comparative efficacy and harm of different PPIs. For outcomes graded as low quality – future research is very likely to have an important impact on our confidence in the estimate and may change the estimate. For outcomes graded as very low quality – we are very uncertain about the estimate.
Adequately powered randomized controlled trials comparing different PPIs are needed to evaluate long term benefits and harm of PPI therapy and should report on all outcome measures specified in the hierarchy of health outcomes in this review.
Trials in specific subgroups based on baseline characteristics (age, gender, race, BMI, smoking, alcohol consumption, genotype of CYP2C19 and CYP3A4 liver enzyme, associated co-morbidity; concomitant medications, severity of grade of GERD; and presence of H. pylori infection) are required to determine if differences in efficacy exist between different PPIs.
Specific adverse effects associated with long-term therapy using different PPIs need to be studied in high quality, prospective well designed long term observational studies incorporating data on dosage and duration of treatment with extended follow up.