Department of Pharmacy, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, People's Republic of China.
School of Medicine, South China University of Technology, Guangzhou, 511442, Guangdong, People's Republic of China.
Sci Rep. 2024 Oct 10;14(1):23699. doi: 10.1038/s41598-024-75271-x.
Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13-131) and 9 days (range: 7-27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events.
免疫检查点抑制剂(ICIs)已成为各种恶性肿瘤的重要治疗方式。由于过度的炎症和免疫反应,会发生免疫相关不良事件(irAEs),如皮疹、瘙痒、肺炎、肝炎、甲状腺功能减退、甲状腺功能亢进和疲劳。获得性免疫性血小板减少症是一种罕见的 irAE,可导致严重的血小板计数降低和出血。我们对美国食品和药物管理局不良事件报告系统(FAERS)中的数据进行了回顾性观察性分析。我们搜索了 FAERS 中记录的所有报告,涵盖了 2011 年第一季度至 2023 年第四季度的目标药物。使用报告比值比(ROR)、比例报告比(PRR)、贝叶斯置信传播神经网络(BCPNN)和多项伽马泊松收缩器(MGPS)算法进行信号分析。非参数检验用于比较不同方案引起的血小板减少性骨折的发病时间。FAERS 数据库中有 404 例免疫性血小板减少症报告。免疫性血小板减少症与除 tremelimumab 以外的所有 ICI 相关,并且通过所有 4 种方法都检测到了信号。PD-1、PD-L1 和 CTLA-4 抑制剂引起的免疫性血小板减少症的中位发病时间分别为 47 天(范围:21-139.2)、21 天(范围:13-131)和 9 天(范围:7-27)。Weibull 形状参数检验显示,pembrolizumab、durvalumab 和 ipilimumab 引起的血小板减少症呈随机失效型,nivolumab 和 atezolizumab 引起的血小板减少症呈早期失效型。ICI 引起的血小板减少症与大多数 ICI 相关的报告信号具有显著的统计学意义。免疫性血小板减少症在男性、老年人和亚洲人群中发病率较高,PD-1 抑制剂是最常见的病因。临床医生应注意潜在严重不良事件的迹象。