Disproportionality Analysis of Biliary Adverse Events Associated with Fibrates Using the JADER and FAERS Databases

Satoko Watanabe¹Kyosuke Nagura¹Naoto Okada²Taro Watanabe^3,4Hidenori Sagara^1,4*

• ¹Division of Medical Safety Science, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Japan
• ²Pharmacy Department, Yamaguchi University Hospital, Ube, Japan
• ³Department of Pharmacy, Yamaguchi Prefectural Grand Medical Center, Hofu, Japan
• ⁴Division of Medical Safety Science, Graduate School of Pharmaceutical Sciences, Sanyo-Onoda, Japan

Introduction: Fibrates are effective triglyceride-lowering drugs, but they may affect bile acid metabolism, raising concerns about biliary adverse drug events (ADEs). Objective: In this study, we used spontaneous reporting system databases to evaluate the association between fibrates and biliary ADEs. This study has been reported in accordance with the Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance guidelines. Methods: We used data from the Japanese Adverse Drug–Event Report (JADER) and the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) databases. The signal detection metrics employed were reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and Gamma–Poisson Shrinker. We also conducted stratified disproportionality and time-to-onset analyses. Results: We identified 58 and 260 unique individual case safety reports from the JADER and FAERS databases, respectively. Primary disproportionality analysis of all fibrates in the JADER dataset revealed an ROR of 3.74 [2.88–4.85]. All other signal detection metrics also exhibited statistically significant associations. In the stratified disproportionality analysis, pemafibrate showed significant signals across all strata, confirming the robustness of the signal. In the Weibull analysis for pemafibrate, the shape parameter (β) was 1.59 [1.17–2.56], indicating an increasing trend in ADE reporting with continued pemafibrate use. Conclusion: A significant signal for biliary ADEs was detected for fibrates in both databases, with a particularly consistent association for pemafibrate. Regular hepatobiliary monitoring and individualized patient management are recommended.