PGI28 INFLUENCE OF PUBLISHED STUDIES ON SPONTANEOUS REPORTING OF ADVERSE KIDNEY EVENTS WITH PROTON PUMP INHIBITORS (PPIS)

Abstract

Proton Pump Inhibitors (PPIs) are widely used among the U.S. population and are generally considered safe. A few published studies reported kidney-related adverse events (AEs) with PPI use. This study examined the influence of these published studies on spontaneous reporting for PPIs with kidney AE events. The 2004-2018 U.S. FDA Adverse Event Reporting System (FAERS) data were analyzed. Individual PPI’s brand and generic names were used to identify AE reports. The Medical Dictionary for Regulatory Activities (MedDRA) and Standardized MedDRA Queries (SMQs) were used to identify Acute Renal Failure (ARF) and Chronic Kidney Disease (CKD). The year of first publications indicating risk of ARF (Klepser 2013) and CKD (Lazarus 2016) were used as the cut-off time points to analyze the relative reporting rates (disproportionality analyses using the reporting odds ratio (ROR) with 95% confidence interval (CI)) of these AEs before and after of these publications, as well as the entire study period. Overall, the ROR for ARF with all PPIs was 1.89 (95%CI 1.88-1.91); however, before the first publication in 2013, the ROR showed a protective signal (ROR=0.94, 95%CI 0.93-0.96). However, after 2013 the PPIs had an ARF ROR of 2.96 (95% CI 2.94-2.98). Similarly, the overall CKD ROR between 2004-2018 was 1.78 (95%CI 1.77-1.79), but the signal did not exist before 2016 (ROR=1.01, 95%CI 1.00-1.02). Elevation of safety signals for kidney-related AE reports with PPIs were observed after the publications of key studies. These analyses provide a “text-book” example of how publication bias can influence reporting rates of AEs. Future data mining and interpretation of case reports should carefully consider this problem in risk assessment.