Table 1_Disproportionality analysis of biliary adverse events associated with fibrates using the JADER and FAERS databases.xlsx

IntroductionFibrates are effective triglyceride-lowering drugs, but they may affect bile acid metabolism, raising concerns about biliary adverse drug events (ADEs).
ObjectiveIn 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.
MethodsWe 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.
ResultsWe 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.
ConclusionA 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.

引言
贝特类药物是有效的降甘油三酯药物，但可能影响胆汁酸代谢，由此引发了人们对胆汁型药物不良反应（Adverse Drug Events, ADEs）的担忧。

目的
本研究采用自发呈报系统数据库，评估贝特类药物与胆汁型药物不良反应之间的关联。本研究严格遵循《药物警戒中利用个体病例安全报告开展药物安全信号检测的不均衡性分析报告指南》开展。

方法
本研究使用日本药品不良反应报告数据库（Japanese Adverse Drug–Event Report, JADER）与美国食品药品监督管理局不良事件报告系统（U.S. Food and Drug Administration Adverse Event Reporting System, FAERS）的数据。本研究采用的信号检测指标包括报告比值比（Reporting Odds Ratio, ROR）、比例报告比、贝叶斯置信传播神经网络以及伽马-泊松收缩器（Gamma–Poisson Shrinker）。此外，本研究还开展了分层不均衡性分析与发病时间分析。

结果
从JADER与FAERS数据库中，本研究分别筛选出58份与260份独立个体病例安全报告。对JADER数据集内所有贝特类药物的初步不均衡性分析显示，其报告比值比为3.74[2.88~4.85]。其余所有信号检测指标均呈现具有统计学意义的关联。在分层不均衡性分析中，培马贝特（pemafibrate）在所有分层亚组中均表现出显著信号，证实了该信号的稳健性。针对培马贝特的威布尔（Weibull）分析显示，其形状参数（β）为1.59[1.17~2.56]，提示随着培马贝特持续用药，药物不良反应报告量呈上升趋势。

结论
两项数据库中均检测到贝特类药物与胆汁型药物不良反应相关的显著信号，其中培马贝特的关联尤为稳定。本研究建议开展规律的肝胆监测，并实施个体化患者管理。