Long PingPing, Li Siyu, Pan Lingyun, Wang Yuanqiang, Chen Wanyi, Wang Xiaoxiao
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China.
Department of Pharmacy, Chongqing University Cancer Hospital, Chongqing, China.
Front Pharmacol. 2024 May 3;15:1378010. doi: 10.3389/fphar.2024.1378010. eCollection 2024.
As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events.
We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated.
In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure ( = 277) and embolic and thrombotic events, venous ( = 446) were the most frequently reported CVD-related AEs in ADCs.
By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.
抗体药物偶联物（ADCs）作为一种新型药物制剂，广泛应用于各类癌症治疗。然而在临床上，人们对其引发的心血管疾病（CVD）缺乏关注，对实际情况也缺乏研究。我们利用美国食品药品监督管理局不良事件报告系统（FAERS）数据库，分析抗肿瘤ADCs的上市后数据，以确定与心血管事件风险相关的危险因素和药物，确保其临床安全应用。
我们使用OpenVigil 2.1对药物上市至2023年第二季度期间向FAERS数据库报告的不良事件（AEs）进行数据库查询。心血管不良事件（AEs）使用监管活动医学标准词典（MedDRA）查询（SMQs）分为14个狭义类别，并计算报告比值比（ROR）和比例报告比值（PRR），以报告不同药物与心血管疾病（CVD）风险之间的关联。
在FAERS数据库中，我们研究发现接受ADC治疗的患者中有1863例与CVD相关的AEs。大多数报告来自65岁及以上人群，但也发现大量病例年龄不明。年龄＜18岁、18 - 64岁和≥65岁的抗体药物偶联物（ADCs）相关CVD病例数分别为52例（2.79%）、586例（31.45%）和613例（32.90%）。女性患者比例（834例，44.77%）高于男性患者（752例，40.37%）。不良事件包括死亡（770例报告）、残疾（9例报告）、初次或长期住院（407例报告）和危及生命的反应（187例报告）。在报告的770例死亡病例中，103例（31.7%）与维布妥昔单抗相关，10例（24.4%）与戈沙妥珠单抗相关，22例（19.3%）与恩沃利单抗相关，35例（34.7%）与曲妥珠单抗 emtansine相关。49例（41.2%）病例与泊洛妥珠单抗相关，62例（29%）与曲妥珠单抗德鲁替康相关，423例（54.3%）与吉妥珠单抗奥唑米星相关，66例（38.8%）与伊奈妥单抗相关。在不成比例数量的SMQs中，心力衰竭（ = 277）和栓塞及血栓形成事件，静脉（ = 446）是ADCs中最常报告的与CVD相关的AEs。
通过挖掘FAERS数据库，我们提供了关于ADC使用与心血管相关AEs之间关联的相关信息。ADCs与心血管毒性增加相关，值得进行专门监测和适当管理。需要进一步研究以证实这些发现并评估因果关系。
