Dore David D, DiBello Julia R, Lapane Kate L
Department of Community Health, Brown Medical School, Providence, RI 02903, USA.
Drug Saf. 2007;30(8):697-703. doi: 10.2165/00002018-200730080-00006.
Recent reports have described cases of telithromycin-related hepatotoxicity. The objective of this study is to quantify the effect of telithromycin use on the risk of hepatotoxicity.
We conducted a spontaneous-report case-control study of hepatotoxicity in telithromycin recipients using reports from the US FDA Adverse Event Reporting System. Reports from between 1 January 2005 and 30 June 2005 were examined. Cases included reports of patients with abnormal liver function tests, hepatocellular damage and hepatic impairment, while patients with reported conditions with similar reporting probabilities were considered as controls. The primary outcome measure of the analysis was the reporting odds ratio (ROR) evaluating the a priori hypothesis that telithromycin use confers an elevated risk of hepatotoxicity relative to other agents.
A total of 2219 cases and 20,667 controls were identified. We estimated an ROR for hepatotoxicity associated with telithromycin compared with other agents of 1.82 (95% CI 1.12, 2.96) after controlling for age and gender, approximating an 82% excess risk in users of telithromycin relative to users of other agents.
This analysis is the first to specifically quantify the effect of telithromycin on the risk of hepatotoxicity. Telithromycin use may increase the risk of hepatotoxicity by >80%. Biases inherent in spontaneous reports include under-reporting of events and differential or time-varying reporting due to enhanced clinician awareness. Future studies should employ alternative data sources because of the inherent limitations of passive surveillance systems.
近期报告描述了与泰利霉素相关的肝毒性病例。本研究的目的是量化使用泰利霉素对肝毒性风险的影响。
我们利用美国食品药品监督管理局不良事件报告系统的报告，对接受泰利霉素治疗的患者进行了肝毒性自发报告病例对照研究。对2005年1月1日至2005年6月30日期间的报告进行了审查。病例包括肝功能检查异常、肝细胞损伤和肝功能损害患者的报告，而报告概率相似的疾病患者被视为对照。分析的主要结局指标是报告比值比（ROR），用于评估预先设定的假设，即与其他药物相比，使用泰利霉素会增加肝毒性风险。
共识别出2219例病例和20667例对照。在控制年龄和性别后，我们估计与其他药物相比，泰利霉素相关肝毒性的ROR为1.82（95%可信区间1.12, 2.96），这意味着相对于其他药物使用者，泰利霉素使用者的风险高出约82%。
本分析首次具体量化了泰利霉素对肝毒性风险的影响。使用泰利霉素可能使肝毒性风险增加80%以上。自发报告中固有的偏倚包括事件报告不足以及由于临床医生意识增强导致的差异报告或随时间变化的报告。由于被动监测系统的固有局限性，未来研究应采用其他数据源。
