(63) Potential Unknown Benefits of Rabeprazole: Real-World Evidence Generated Using the REWARD Framework

Publication Number: 737

Background: Several studies have suggested the potential for repurposing proton pump inhibitors (PPIs) for a diverse set of therapeutic areas ranging from cancer to COVID-19. While these studies are largely pre-clinical, data driven, and experimental, evidence of unknown benefits may also come from outcomes observed among patients using PPIs in the real world.

Objectives: In this study, we focus on identifying potential new therapeutic benefits of one PPI, rabeprazole sodium, using real-world data from administrative claims.

Methods: New users of rabeprazole were identified from five sources: the IBM MarketScan© Commercial, Multi-State Medicaid, and Medicare Supplemental Databases, the Optum© De-Identified Clinformatics© Data Mart, and the Japan Medical Data Center database. Outcomes were defined according to Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT) classification system codes and required a diagnosis on two or more distinct dates. A self-controlled cohort design was used to assess the association between rabeprazole and the incidence of all observed disease outcomes. Empirical null distributions constructed from negative control outcomes were used to adjust for systematic error across a large number of effect estimates. Potential benefits were defined as disease outcomes for which rabeprazole was associated with ≥ 30% reduction in incidence (empirically calibrated P ≤ .05) in at least two databases.

Results: 908,121 new users of rabeprazole were identified (average age: 50.6 years, average duration of use: 169 days). Of 25,513 outcomes assessed, five potential benefits were associated with rabeprazole after removing conditions related to GERD: benign hypertension (meta-analytic incidence rate ratio (IRR): 0.68, 95% CI: 0.48-0.94), essential hypertension (IRR: 0.55, 95% CI: 0.40-0.77), hyperlipidemia (IRR: 0.60, 95% CI: 0.43-0.85), acute myocardial infarction of the inferior wall (IRR: 0.37, 95% CI: 0.417-0.81), and malaise (IRR: 0.69, 95% CI: 0.48-0.99).

Conclusions: Our approach identified five hypothetical new therapeutic benefits of rabeprazole, of which three (benign hypertension, essential hypertension, and hyperlipidemia) had some degree of prior evidence and two were novel (acute MI of inferior wall and malaise). Further study of these associations may be warranted, perhaps using alternative study designs or with comparison to other products.