Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Centre for Applied Biomedical Research (CRBA), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Br J Clin Pharmacol. 2021 Mar;87(3):1533-1540. doi: 10.1111/bcp.14459. Epub 2020 Jul 26.
Given its approval for the treatment of cytokine release syndrome, tocilizumab is under investigation in severe coronavirus disease-2019. To characterize serious adverse events (AEs) with tocilizumab, we queried the worldwide FDA Adverse Event Reporting System and performed disproportionality analysis, selecting only designated medical events (DMEs) where tocilizumab was reported as suspect, with a focus on hepatic reactions. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL 95% CI) > 1. A total of 2,433 reports of DMEs were recorded with tocilizumab, mainly in rheumatic diseases. Statistically significant RORs emerged for 13 DMEs, with drug-induced liver injury (n = 91; LL 95% CI 3.07), pancreatitis (151; 1.41), and pulmonary fibrosis (222; 7.21) as unpredictable AEs. A total of 174 cases of liver-related DMEs were retrieved (proportion of deaths = 18.4%), with median onset of 27.5 days. These serious unpredictable reactions occurring in chronic real-world tocilizumab use may support patient care and monitoring of ongoing clinical trials.
鉴于托珠单抗已获准用于治疗细胞因子释放综合征，目前正在研究其在严重的 2019 冠状病毒病中的应用。为了描述托珠单抗的严重不良事件（AE），我们查询了全球 FDA 不良事件报告系统，并进行了不相称性分析，仅选择了将托珠单抗报告为可疑药物的指定医疗事件（DME），重点关注肝脏反应。计算了报告比值比（ROR），置信区间下限（LL 95%CI）>1 被认为具有统计学意义。共记录了 2433 例托珠单抗相关 DME 报告，主要发生在风湿性疾病中。13 种 DME 的 ROR 具有统计学意义，其中药物性肝损伤（n=91；LL 95%CI 3.07）、胰腺炎（151；1.41）和肺纤维化（222；7.21）为不可预测的 AE。共检索到 174 例与肝脏相关的 DME 病例（死亡比例=18.4%），中位发病时间为 27.5 天。这些在慢性真实世界中使用托珠单抗时发生的严重不可预测反应可能支持患者的护理和正在进行的临床试验监测。
