基于美国FAERS的PD-1/PD-L1抑制剂导致肺炎的数据分析

目的：基于美国FDA不良事件报告系统（FDA adverse event reporting system，FAERS）对PD-1/PD-L1抑制剂导致肺炎的发生情况进行数据分析，为PD-1/PD-L1抑制剂的临床安全应用提供参考。方法：利用OpenFDA平台，收集2015年第1季度至2020年第3季度FAERS数据库中首要怀疑药物为阿替利珠单抗、度伐利尤单抗、纳武单抗和帕博利珠单抗，不良事件为肺炎的报告，采用报告比值比法（ROR）评价4种药物导致不同类型肺炎的风险大小。结果：PD-1/PD-L1抑制剂导致肺炎的报道共有7 444份，包括阿替利珠单抗718份（9.65%），度伐利尤单抗1 109份（14.90%），纳武单抗3 627份（48.72%），帕博利珠单抗1 990份（26.73%），涉及患者7 268人，共检测出70个不良事件的风险信号，其中阿替利珠单抗13个，度伐利尤单抗11个，纳武单抗26个，帕博利珠单抗20个。不良事件以放射性肺炎、免疫介导性肺炎和感染性肺炎为主。结论：阿替利珠单抗、度伐利尤单抗、纳武单抗和帕博利珠单抗均与肺炎的发生相关，其中度伐利尤单抗导致肺炎的风险最高。使用时应注意感染性肺炎，放射性肺炎和免疫相关性肺炎的发生，尤其是65岁以上老年男性患者。

Data analysis of the risks of pneumonia/pneumonitis induced by PD-1/PD-L1 inhibitors based upon FAERS database

OBJECTIVE To analyze the risks of pneumonia/pneumonitis induced by PD-1/PD-L1 inhibitors based upon the FDA adverse event reporting system (FAERS) to provide references for safe clinical dosing.METHODS The pneumonia/pneumonitis reports induced by 4 kinds of PD-1/PD-L1 inhibitors as "atezolizumab" "durvalumab" "nivolumab" and "pembrolizumab" were utilized as the first suspected drug from the database of FAERS from 2015 to the third quarter of 2020. The report odd ratio (ROR) method was employed.RESULTS A total 7 444 adverse event reports involving 7 268 patients were retrived. There were 718 reports of atezolizumab, 1 109 reports of durvalumab, 3 627 reports of Nivolumab and 1 990 reports of pembrolizumab. And 70 adverse event signals were detected. Among them,there were positive signals of atezolizumab (n=13), durvalumab (n=11), nivolumab (n=26) and pembrolizumab (n=20). Adverse events with high signal intensity were mostly radiation pneumonitis, immune-mediated pneumonitis and infectious pneumonia.CONCLUSION Atezolizumab, durvalumab, nivolumab and pembrolizumab can cause pneumonia/pneumonitis. Durvalumab has the highest risk of pneumonia/pneumonitis. Attention should be paid to infectious pneumonia, radiation pneumonitis and immune-associated pneumonitis, especially in elders aged over 65 years.