背景：免疫检查点抑制剂（ICIs）已被报道会引起肺孢子菌肺炎（PJP），但这仅限于病例报告。ICIs引起的PJP临床特征仍然大多未知。本研究旨在调查PJP与ICIs之间的关系，并描述其临床特征。方法：通过FAERS记录的“肺孢子菌肺炎”首选词，识别了2004年1月至2022年12月录入的PJP报告。描述了人口统计学和临床特征，并通过调整信号来排除污染物免疫抑制剂和已有疾病，使用传统化疗和靶向治疗作为比较剂，通过报告比率比（ROR）和信息组分（IC）来评估不均衡信号。进行了系统的文献回顾，以描述ICIs发表的PJP报告的临床特征。采用Bradford Hill标准进行证据的全球评估。结果：我们识别了677份与ICIs相关的PJP报告，其中300例（44.3％）PJP病例死亡。在FAERS数据库中，尼伯露莫（IC025 2.05），帕博利珠单抗（IC025 1.88），伊匹利莫（IC025 1.43），阿特珂珠单抗（IC025 0.36），杜伐替尤单抗（IC025 1.65），尼伯露莫加伊匹利莫（IC025 1.59）与其他药物相比具有显著信号。排除增加PJP易感性的已有疾病和免疫抑制剂后，与尼伯露莫、帕博利珠单抗、杜伐替尤单抗、尼伯露莫加伊匹利莫相关的PJP信号仍然坚固（IC025> 0）。与其他抗癌方案相比，尽管所有ICIs显示出比化疗更低的PJP不均衡信号，但尼伯露莫（IC025 0.33，p <0.001），帕博利珠单抗（IC025 0.16，p <0.001）这两种PD-1抑制剂与靶向治疗相比在PJP方面具有更高的信号。在与ICIs相关的PJP文献中，10份已发表的病例报告中报告了15例PJP病例。在PJP被诊断之前，15例中的12例（80.0％）接受了PD-1抑制剂。结论：通过FAERS和已发表的病例报告的联合分析，我们确定ICIs可能与PJP有关，尤其是在男性> 65岁时。在考虑混淆因素后，PD-1抑制剂与PD-L1 / CTLA-4抑制剂以及靶向治疗相比出现了明显的不均衡信号。需要进一步研究验证我们的发现。 版权所有 ©2023 Xia，Gong，Wang，Liu，Zhao，Guo，Zhang，Sarangdhar，Noguchi和Yan。

Background: Pneumocystis jirovecii pneumonia (PJP) has been reported with ICIs but limited to case reports. The clinical features of PJP with ICIs remain mostly unknown. This study aims to investigate the association of PJP with ICIs and describe clinical features. Methods: Reports of PJP recorded in FAERS (January 2004-December 2022) were identified through the preferred term "Pneumocystis jirovecii pneumonia". Demographic and clinical features were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC), using traditional chemotherapy and targeted therapy as comparators, and adjusting signals by excluding contaminant immunosuppressive drugs and pre-existing diseases. A systematic literature review was conducted to describe clinical features of published PJP reports with ICIs. Bradford Hill criteria was adopted for global assessment of the evidence. Results: We identified 677 reports of PJP associated with ICIs, in which 300 (44.3%) PJP cases with fatal outcome. Nivolumab (IC025 2.05), pembrolizumab (IC025 1.88), ipilimumab (IC025 1.43), atezolizumab (IC025 0.36), durvalumab (IC025 1.65), nivolumab plus ipilimumab (IC025 1.59) have significant signals compared to other drugs in FAERS database. After excluding pre-existing diseases and immunosuppressive agents which may increase susceptibility of PJP, the signals for PJP associated with nivolumab, pembrolizumab, durvalumab, nivolumab plus ipilimumab remained robust (IC025 > 0). When compared to other anticancer regimens, although all ICIs showed a lower disproportionate signal for PJP than chemotherapy, nivolumab (IC025 0.33, p < 0.001), pembrolizumab (IC025 0.16, p < 0.001), both PD-1 inhibitors, presented a higher signal for PJP than targeted therapy. Male gender (IC025 0.26, p < 0.001) and age >65 years (IC025 0.38, p < 0.001) were predominant in PJP cases associated with across all ICIs. In literature, 15 PJP cases associated with ICIs were reported in 10 published case reports. 12 of 15 (80.0%) of cases received PD-1 inhibitors before PJP was diagnosed. Conclusion: By the combined analysis of post-marketing data from FAERS and published case reports, we identified ICIs may be associated with PJP, especially in males aged >65years. After accounting for confounders, PD-1 inhibitors emerged with a robust disproportionality signal when compared to PD-L1/CTLA-4 inhibitors as well as targeted therapy. Further research is warranted to validate our findings.Copyright © 2023 Xia, Gong, Wang, Liu, Zhao, Guo, Zhang, Sarangdhar, Noguchi and Yan.