Gérard Alexandre O, Merino Diane, Benzaquen Jonathan, Destere Alexandre, Borchiellini Delphine, Gosset Clément, Rocher Fanny, Andreani Marine, Marquette Charles-Hugo, Montaudié Henri, Drici Milou-Daniel, Sicard Antoine
Department of Nephrology-Dialysis-Transplantation, Université Côte d'Azur, University Hospital Centre of Nice, Nice, France.
Department of Clinical Pharmacology, Université Côte d'Azur, University Hospital Centre of Nice, Nice, France.
Front Immunol. 2025 Jan 22;16:1514033. doi: 10.3389/fimmu.2025.1514033. eCollection 2025.
Transplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of AR between the different ICI classes remains to be defined.
VigiBase (WHO's pharmacovigilance database) was queried for reports of AR involving CTLA4, PD1, or PDL1 inhibitors. Disproportionality analysis compares the proportion of reports with a specific adverse drug reaction (ADR) and a given drug to the proportion of reports with the same ADR and other drugs. A lower 95% confidence interval for the Information Component (IC) >0 suggests a signal. The comparative Reporting Odds Ratios (ROR) for AR, between PD1 and PDL1 inhibitors, was calculated.
We gathered 159 AR involving an ICI, especially nivolumab (73, 45.9%), mostly affecting kidneys (87, 54.7%). Median time to onset: 28 days. Fatal outcome: 36 reports (22.6%). ICI were significantly associated with AR: IC=1.7 [1.4;1.9]. Specifically, PD1 inhibitors yielded an IC of 2.0 [1.7;2.2] (152 reports observed compared to 38 expected). By contrast, the IC of PDL1 inhibitors was negative: -2.6 [-6.4;-1.0] (1 observed, 9 expected). The comparative ROR of PD1 compared to PDL1 inhibitors was 33.7 [4.7;240.9] (p=0.0005).
We confirm the association between ICI treatment and AR. Notably, PDL1 inhibitors showed surprisingly low AR reports compared to CTLA4 and PD1 inhibitors. Further prospective studies are warranted to confirm whether PDL1 inhibitors indeed reduce AR risk compared to other ICI.
由于免疫抑制治疗，移植受者面临更高的癌症死亡率。免疫检查点抑制剂（ICI）提高了生存率，但关于这些药物在移植受者中的使用数据却很稀少。ICI可能引发同种异体移植排斥反应，但不同ICI类别之间的急性排斥（AR）绝对风险仍有待确定。
在VigiBase（世界卫生组织药物警戒数据库）中查询涉及CTLA4、PD1或PDL1抑制剂的AR报告。不成比例分析将特定药物不良反应（ADR）报告与给定药物的比例与具有相同ADR和其他药物的报告比例进行比较。信息成分（IC）的较低95%置信区间>0表明存在信号。计算了PD1和PDL1抑制剂之间AR的比较报告比值比（ROR）。
我们收集了159例涉及ICI的AR，尤其是纳武单抗（73例，45.9%），主要影响肾脏（87例，54.7%）。发病中位时间：28天。致命结局：36例报告（22.6%）。ICI与AR显著相关：IC=1.7[1.4；1.9]。具体而言，PD1抑制剂的IC为2.0[1.7；2.2]（观察到152例报告，预期38例）。相比之下，PDL1抑制剂的IC为阴性：-2.6[-6.4；-1.0]（观察到1例，预期9例）。PD1与PDL1抑制剂的比较ROR为33.7[4.7；240.9]（p=0.0005）。
我们证实了ICI治疗与AR之间的关联。值得注意的是，与CTLA4和PD1抑制剂相比，PDL1抑制剂的AR报告出奇地少。有必要进行进一步的前瞻性研究，以确认与其他ICI相比，PDL1抑制剂是否确实降低了AR风险。
