目的 基于美国食品药品管理局不良事件报告系统（FAERS）数据库，对替西木单抗联合度伐利尤单抗联合治疗所致免疫相关不良事件（irAEs）进行信号挖掘与分析，为临床安全用药提供参考。方法 提取FAERS数据库中自2018年第1季度—2025年第3季度两药联合应用的相关不良事件报告。采用报告比值比（ROR）等4种比例失调分析法进行信号挖掘，经多重比较校正结果筛选阳性信号，按发生频次和强度进行排序，并重点分析其中irAEs信号的分布特征。结果 共筛选出联合用药不良事件报告5 004例，涉及2 585位患者，男性占比63.7%，65岁以上年龄段报告例数最多，中位不良事件诱发时间为32 d，多集中于用药后30 d内（20.6%）。在首选术语（PT）层面共检测到176个阳性信号，分布于19个系统器官分类（SOCs），主要集中在各类检查、胃肠、内分泌及肝胆系统疾病等。发生频次前5位的PT依次为腹泻、死亡、恶性肿瘤进展、细胞因子释放综合征、发热；信号强度前5位的PT分别为食管纵隔瘘、肝癌破裂、免疫毒性、维生素K缺乏或拮抗剂II诱导产生的蛋白升高、疑似药物性肝损伤。进一步识别irAEs阳性信号35个，共523例报告，涉及胃肠道、肝胆、皮肤、内分泌及心肺等系统，其中CRS、免疫介导性小肠结肠炎、免疫介导性肝病等较为突出。结论 替西木单抗联合度伐利尤单抗建议将治疗首月作为重点监测窗口。临床风险管理可采用高频事件规范化识别与分级处理、高强度信号事件强调鉴别诊断前移与严密监护，重点关注胃肠道、肝胆、皮肤、内分泌及心肺等系统不良反应，并对食管纵隔瘘、肝癌破裂、肿瘤超进展等罕见但潜在严重事件保持警惕。

Objective To investigate immune-related adverse events (irAEs) associated with tremelimumab plus durvalumab combination therapy by mining and analyzing signals from the FAERS database, thereby providing evidence for clinical medication safety. Methods Relevant adverse event reports associated with the combined use of the two drugs from the first quarter of 2004 to the third quarter of 2025 were extracted from the FAERS database. Signal mining was performed using four disproportionality analysis methods, including the reporting odds ratio (ROR). Positive signals were screened based on results adjusted for multiple comparisons, ranked by frequency and strength of occurrence, with a focus on analyzing the distribution characteristics of irAE signals. Results A total of 5 004 adverse drug event reports associated with the combination therapy were screened, involving 2 585 patients. Among them, males accounted for 63.7%, and the age group of 65 years and older had the highest number of reports. The median time to onset of adverse drug events was 32 days, with a concentration of reports within 30 days after treatment initiation (20.6%). At the preferred term (PT) level, 176 positive signals were detected, distributed across 19 system organ classes (SOCs), primarily in categories such as investigations, gastrointestinal disorders, endocrine disorders, and hepatobiliary diseases. The top five PTs by frequency were diarrhea, death, malignant neoplasm progression, cytokine release syndrome, and pyrexia. The top five PTs by signal strength were esophago-mediastinal fistula, hepatic rupture, immune toxicity, protein induced by vitamin K absence or antagonist-II (PIVKA-II) elevation, and suspected drug-induced liver injury. Further analysis identified 35 irAE-positive signals, involving 523 reports, which affected systems including gastrointestinal, hepatobiliary, skin, endocrine, and cardiopulmonary. Among these, cytokine release syndrome, immune-mediated enterocolitis, and immune-mediated hepatitis were particularly prominent. Conclusion The combination therapy of tremelimumab and durvalumab suggesting that the first month of treatment should be considered a critical monitoring window. Clinical risk management may adopt strategies including standardized recognition and graded management for high-frequency events, as well as emphasizing early differential diagnosis and intensive monitoring for high-strength signal events. Particular attention should be paid to adverse reactions involving the gastrointestinal, hepatobiliary, skin, endocrine, and cardiopulmonary systems, while vigilance should be maintained for rare but potentially severe events such as esophago-mediastinal fistula, hepatic rupture, and hyperprogression.

R979.1

国家自然科学基金资助项目（82074239）；国家中医药管理局中医药创新团队及人才支持计划（ZYYCXTD-C-202205）；中国中医科学院科技创新工程重大攻关项目（CI2021A01801）；中国中医科学院中央级公益性科研院所基本科研业务费项目（ZZ15-XY-PT-16）；中央高水平中医医院临床研究和成果转化能力提升项目（HLCMHPP2023085）