Abstract：
BACKGROUND: Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date.
METHODS: The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC025) > 0 or ROR (ROR025) > 1 with at least 3 reports was considered statistically significant.
RESULTS: Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC025/ROR025 for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC025 for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of \"fatal\" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT.
CONCLUSIONS: ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.
METHODS: The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC025) > 0 or ROR (ROR025) > 1 with at least 3 reports was considered statistically significant.
RESULTS: Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC025/ROR025 for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC025 for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of \"fatal\" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT.
CONCLUSIONS: ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.
摘要：
背景：尽管免疫检查点抑制剂（ICIs）与血管生成抑制剂（AGIs）的组合已越来越多地用于癌症，迄今为止,在现实环境中,联合治疗对免疫相关不良事件(irAEs)的影响尚未得到很好的阐明.
方法：回顾性查询2014年至2022年FDA不良事件报告系统（FAERS）数据库，以提取被称为标准化MedDRA查询（SMQs）的irAE报告，首选术语(PT)和系统器官类别(SOC)。要进行不相称性分析，计算信息成分(IC)和报告比值比(ROR),对于IC(IC025)>0或ROR(ROR025)>1且至少3份报告的95%置信区间(CI)下限被认为具有统计学意义.
结果：与单独的ICIs相比，ICIs+AGIs显示irAE-SMQ的IC025/ROR025较低（2.343/5.082与1.826/3.563）。关于irAE-PT，ICIs+AGIs中具有显著价值的irAE-PT少于单独的ICIs(57vs.150个PT）和ICIs+AGIs中大多数PT（88%）的较低信号值。此外，与单独使用ICIs相比，ICIs+AGIs(11/13)中大多数Es-SOCs的IC025较低。至于IRAE的结果，ICIs+AGIs对irAE-SMQ的“致命”频率低于单独的ICIs(4.88%与7.83%），所以在心脏疾病(SOC)中(15.45%vs.26.37%），和呼吸，胸部和纵隔疾病(SOC)(13.74%vs.20.06%）。同样，与ICIs+CT相比,ICIs+AGIs+化疗(CT)中的irAE发生率更低,病死率更低.
结论：无论是否使用CT，与单独使用ICIs相比，ICIs联合AGIs可降低大多数irAE的发生率和死亡率。
方法：回顾性查询2014年至2022年FDA不良事件报告系统（FAERS）数据库，以提取被称为标准化MedDRA查询（SMQs）的irAE报告，首选术语(PT)和系统器官类别(SOC)。要进行不相称性分析，计算信息成分(IC)和报告比值比(ROR),对于IC(IC025)>0或ROR(ROR025)>1且至少3份报告的95%置信区间(CI)下限被认为具有统计学意义.
结果：与单独的ICIs相比，ICIs+AGIs显示irAE-SMQ的IC025/ROR025较低（2.343/5.082与1.826/3.563）。关于irAE-PT，ICIs+AGIs中具有显著价值的irAE-PT少于单独的ICIs(57vs.150个PT）和ICIs+AGIs中大多数PT（88%）的较低信号值。此外，与单独使用ICIs相比，ICIs+AGIs(11/13)中大多数Es-SOCs的IC025较低。至于IRAE的结果，ICIs+AGIs对irAE-SMQ的“致命”频率低于单独的ICIs(4.88%与7.83%），所以在心脏疾病(SOC)中(15.45%vs.26.37%），和呼吸，胸部和纵隔疾病(SOC)(13.74%vs.20.06%）。同样，与ICIs+CT相比,ICIs+AGIs+化疗(CT)中的irAE发生率更低,病死率更低.
结论：无论是否使用CT，与单独使用ICIs相比，ICIs联合AGIs可降低大多数irAE的发生率和死亡率。
