针对三种免疫检查点蛋白的治疗性抗体已应用于各种恶性肿瘤的治疗。包括小细胞和非小细胞肺癌,黑色素瘤,肾细胞癌,和其他人。这些治疗通过重新激活细胞毒性T细胞来对抗癌症。然而,发现这种作用方式与广泛的免疫相关不良事件(irAE)有关,包括肺炎,结节病,心肌炎,肾炎,结肠炎,和肝炎。根据他们的严重程度,这些IRAE通常需要暂停或停止治疗,在极少数情况下,可能导致死亡。我们分析了超过1,900万份报告,并从接受免疫检查点抑制剂治疗的患者中确定了超过8万份不良事件报告,这些不良事件报告已提交给食品和药物管理局的不良事件报告系统MedWatch。关于pembrolizumab的报告,Nivolumab,cemiplimab,阿维鲁单抗,durvalumab,阿替珠单抗,和ipilimumab显示,在7种治疗方法中,5种治疗方法的irAE与并发传染病之间存在显著的统计学关联.此外,在所有三种类型的检查点抑制剂和五个单独的治疗剂队列中的每一个中,关联趋势都得到了保留。而其余两个显示出相同的趋势,但是置信区间增加了,由于记录数量不足。
Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration\'s Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab,
atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records.