Strombom Indiana, Wernicke Joachim F, Seeger John, D'Souza Deborah N, Acharya Nayan
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Curr Drug Saf. 2008 May;3(2):154-62. doi: 10.2174/157488608784529215.
Present results from two hepatic safety studies conducted within 20 months after duloxetine launch.
Signal detection based on spontaneous reports to the FDA adverse event reporting system (AERS) and on a comparison of duloxetine and venlafaxine in the i3 Drug Safety Aperio claims database, using measures of disproportionality and incidence rate ratio, respectively.
In AERS all antidepressants had some degree of association with hepatic injury, in that at least one hepatic event was disproportionately represented for each drug. Signals were detected for duloxetine cases analyzed against full and antidepressant-only backgrounds. These signals corresponded to labeled events or events investigated during ongoing surveillance. Using a duloxetine fatal-case series, disproportional representation of clinically serious events was detected relative to both backgrounds, but the signals were refuted upon independent expert panel case review. The Aperio study showed no difference in hepatic injury between duloxetine and venlafaxine initiators after proper control for baseline risks, suggesting differential prescribing of duloxetine, perhaps preferentially as second-line therapy in some initiators.
No new signals were identified in Aperio. New signals detected through AERS were refuted upon independently conducted case-level investigation. Hepatic signals arising from spontaneously reported data must be clarified through subsequent systematic investigation.
呈现度洛西汀上市后20个月内进行的两项肝脏安全性研究的结果。
基于向美国食品药品监督管理局不良事件报告系统（AERS）的自发报告，以及在i3药物安全性Aperio索赔数据库中对度洛西汀和文拉法辛进行比较，分别采用不成比例性和发病率比的测量方法进行信号检测。
在AERS中，所有抗抑郁药都与肝损伤有一定程度的关联，因为每种药物至少有一种肝脏事件的呈现不成比例。针对全部背景和仅抗抑郁药背景分析度洛西汀病例时检测到了信号。这些信号对应于标签事件或正在进行的监测中调查的事件。使用度洛西汀致命病例系列，相对于两种背景均检测到临床严重事件的不成比例呈现，但在独立专家小组病例审查后这些信号被驳回。Aperio研究表明，在适当控制基线风险后，度洛西汀和文拉法辛起始者的肝损伤无差异，这表明度洛西汀的处方存在差异，可能在一些起始者中优先作为二线治疗药物。
在Aperio中未发现新的信号。通过AERS检测到的新信号在独立进行的病例水平调查后被驳回。自发报告数据产生的肝脏信号必须通过后续的系统调查加以澄清。
