阿替利珠单抗联合贝伐珠单抗的毒性负荷研究：基于FAERS数据库挖掘与分析

Analysis of toxicity burden for atezolizumab plus bevacizumab based on FAERS database mining and analysis

关键词:  阿替利珠单抗  贝伐珠单抗  FAERS 数据库  毒性负荷

Key words:  Atezolizumab  Bevacizumab  FAERS database  toxicity burden

摘要:

目的 阿替利珠单抗联合贝伐珠单抗是治疗原发性肝癌的一线方案。然而,两者联用的不良事件尚未在真实世界研究中进行安全性分析。本研究对FAERS数据库进行挖掘与分析,探讨两者联合使用的毒性负荷,为临床安全用药提供理论依据。方法 基于2004年1季度至2022年4季度的FAERS数据,采用比例失衡法和组合风险比模型来挖掘不良事件信号,并分析阿替利珠单抗联合贝伐珠单抗相关不良事件的人口信息学特征、毒性负荷、重要医学事件信号及新信号。结果 共提取74192 份不良事件报告,其中阿替利珠单抗13414份,贝伐珠单抗56054份,阿替利珠单抗联合贝伐珠单抗4724份。其中,两者联用不良事件报告男性发生率较高为57.79%,以＞65岁年龄段报告例数最多(n=1912,40.47%)。三组不良事件最常见结果均为住院,最不常见为永久缺陷。中位发病时间分别40天、58天和41天。阿替利珠单抗联合贝伐珠单抗共检测353个阳性信号,其中83个毒性负荷信号,63个重要医学事件信号及23个新信号,主要涉及胃肠系统疾病、肝胆系统疾病、感染及侵染类疾病等。结论 本研究基于FAERS数据库分析了阿替利珠单抗联用贝伐珠单抗出现的不良信号,建议临床用药时应警惕相关不良反应的发生,并做好用药监护。

Abstract:

The combination of atezolizumab and bevacizumab has been the first-line treatment of advanced hepatocellular carcinoma. However, adverse events associated with atezolizumab plus bevacizumab have not been analyzed for safety in real-world studies. This study explores the relationship between the combination of the two and toxicity burden based on the FAERS database to provide a theoretical basis for the rational and safe clinical use of the drug. METHODS Based on the FAERS database from the 1st quarter of 2004 to the 4th quarter of 2022, disproportionality analysis and Combination Risk Ratio Model were used to mine the adverse event signals and analyze the demographic characteristics, toxicity burden， Important Medical Event signals and new signals of adverse events associated with atezolizumab plus bevacizumab. RESULTS A total of 74,192 ADEs adverse event reports were extracted, including 13,414 for atezolizumab, 56,054 for bevacizumab, and 4,724 for atezolizumab plus bevacizumab. The incidence of adverse events reported for atezolizumab plus bevacizumab was higher in males at 57.79%, with the highest number of cases reported in the age group >65 years (n=1,912, 40.47%). Outcomes were most common for hospitalization and least common for required intervention in these groups. The median time to onset was 40, 58 and 41 days in the three groups, respectively. A total of 353 positive signals were detected for atezolizumab plus bevacizumab, including 83 toxicity burden signals, 63 important medical event signals and 23 new signals, mainly involving gastrointestinal disorders, hepatobiliary disorders and infections and infestations. CONCLUSION This study analyzed the adverse signals of atezolizumab plus bevacizumab based on FAERS database, and suggested that the clinical use of the drug should be alert to the occurrence of related adverse reactions, rational use of the drug, and appropriate medication monitoring.