■免疫检查点抑制剂（ICIs）彻底改变了癌症疗法。然而,免疫相关不良事件(irAE)增加发病率和死亡率,从而限制治疗效用.尚未系统地描述整个肺irAE谱的真实世界发病率。本研究的目的是评估发生肺部感染的风险（肺炎，胸膜事件[即，积液和胸膜炎]，气道疾病恶化[即，支气管炎和支气管扩张]，和结节病)暴露于五种常用的ICIs：nivolumab，pembrolizumab,durvalumab,阿维鲁单抗,和阿妥珠单抗。
我们对食品和药物管理局不良事件报告系统（FAERS）药物警戒数据库进行了回顾性审查。我们收集了2012年至2021年的数据来评估肺部感染的风险，并使用Open-Vigil进行了不成比例的分析。用于分析药物警戒数据的软件包，计算报告赔率比(ROR)。我们使用95%CI来评估ROR的精确度。大于1的ROR和95%CI的上限指示统计学显著性。
■2012年至2021年期间，FAERS共报告了17,273,403起事件。其中,88,099（0.5％）归因于PD-1（程序性细胞死亡蛋白1）抑制剂，21,905（0.1％）归因于PD-L1（程序性死亡配体1）抑制剂。使用感兴趣的ICI的最常见适应症是肺癌：PD-1抑制剂共2832例（46.70%），PD-L1抑制剂共1311例（70.9%）。在抗PD-1组中,2342例(38.6%)患者住院,1962例(32.4%)患者死于肺部不良事件.在PD-L1组中，744例（40.3%）患者住院，520例(28.1%)患者死于该事件.Nivolumab导致最高的统计学显著风险(ROR，10.5；95%CI，10.1-10.9）为肺炎。Avelumab患肺炎的风险较小(ROR，0.2；95%CI，0.2-0.3）。nivolumab的胸膜事件风险最高(ROR，3.6；95%CI，3.4-3.9），其次是派博利珠单抗(ROR，1.8；95%CI；1.6-2.0）（p<0.001），Durvalumab的风险最低，阿替珠单抗,和Avelumab.对于ICI相关结节病，pembrolizumab的风险最为显著(ROR，3.6；95%CI，2.8-4.7），其次是纳武单抗(ROR，2.5；95%CI，1.9-3.5）（p<0.001）。与其他药物相比，所有五种ICI的ROR在气道疾病恶化时小于1。
■使用药物警戒数据库，我们发现ICI治疗后发生多发性肺irAE的风险增加，特别是PD-1抑制剂。需要进一步的工作来研究除肺炎以外的肺irAE的发生率。
UNASSIGNED: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby limit therapeutic utility. The real-world incidence of the entire spectrum of pulmonary irAEs has not been systematically described. The objective of this study is to assess the risk of developing pulmonary irAEs (pneumonitis, pleural events [i.e., effusion and pleurisy], exacerbations of airway disease [i.e., bronchitis and bronchiectasis], and sarcoidosis) with exposure to five commonly used ICIs: nivolumab, pembrolizumab, durvalumab, avelumab, and atezolizumab.
UNASSIGNED: We conducted a retrospective
review of the Food and Drug Administration Adverse Events Reporting System (FAERS) pharmacovigilance database. We collected data from 2012 to 2021 to assess the risk of pulmonary irAEs and performed a disproportionality analysis using Open-Vigil, a software package used for analysis of pharmacovigilance data, to calculate reporting odds ratios (RORs). We used 95% CIs to evaluate the precision of RORs. An
ROR greater than 1 and the upper limit of the 95% CI indicated statistical significance.
UNASSIGNED: A total of 17,273,403 events were reported in FAERS between 2012 and 2021. Of these, 88,099 (0.5%) were attributed to the PD-1 (programmed cell death protein 1) inhibitors and 21,905 (0.1%) to PD-L1 (programmed death ligand 1) inhibitors of interest. The most common indication for using the ICIs of interest was lung cancer: a total of 2832 (46.70%) for the PD-1 inhibitors and 1311 (70.9%) for the PD-L1 inhibitors. In the anti-PD-1 group, 2342 (38.6%) patients were hospitalized, and 1962 (32.4%) patients died from the lung adverse event. In the PD-L1 group, 744 (40.3%) patients were hospitalized, and 520 (28.1%) patients died from the event. Nivolumab resulted in the highest statistically significant risk (ROR, 10.5; 95% CI, 10.1-10.9) for pneumonitis. Avelumab had a lesser risk for pneumonitis (
ROR, 0.2; 95% CI, 0.2-0.3). The risk for pleural events was highest with nivolumab (ROR, 3.6; 95% CI, 3.4-3.9), followed by pembrolizumab (ROR, 1.8; 95% CI; 1.6-2.0) (p < 0.001), with the lowest risks from durvalumab, atezolizumab, and avelumab. For ICI-related sarcoidosis, the risk was most significant with pembrolizumab (
ROR, 3.6; 95% CI, 2.8-4.7), followed by nivolumab (
ROR, 2.5; 95% CI, 1.9-3.5) (p < 0.001). The RORs for all five ICIs were less than 1 for exacerbations of airway diseases as compared with other drugs.
UNASSIGNED: Using a pharmacovigilance database, we found an increased risk of multiple pulmonary irAEs after ICI therapy, particularly with PD-1 inhibitors. Further work is needed to investigate the incidence of pulmonary irAEs other than pneumonitis.
PDF(Pubmed)