免疫检查点抑制剂相关的急性肾损伤：一项药物警戒研究。

Acute kidney injury associated with immune checkpoint inhibitors: A pharmacovigilance study.

作者信息

Zhu Jianhong, Wu Jialing, Chen Pengwei, You Kaiyun, Su Jianan, Gao Ziqing, Bi Zhuofei, Feng Min

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China; Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China; Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, China.

出版信息

Int Immunopharmacol. 2022 Dec;113(Pt A):109350. doi: 10.1016/j.intimp.2022.109350. Epub 2022 Oct 20.

DOI:10.1016/j.intimp.2022.109350

PMID:36272360

Abstract

BACKGROUND

Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database.

METHODS

We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC).

RESULTS

A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death.

CONCLUSIONS

These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.

摘要

背景

急性肾损伤（AKI）是免疫检查点抑制剂（ICI）罕见但严重的不良事件。随着ICI报告的增加，有必要对与ICI相关的AKI有新的认识。我们通过从美国食品药品监督管理局不良事件报告系统（FAERS）数据库中提取数据，进行了一项随机对照试验（RCT）的系统评价和一项真实世界研究。

方法

我们检索了ClinicalTrials.gov以及截至2021年8月的电子数据库（PubMed、Cochrane图书馆、Embase）中可用的RCT中与ICI相关的AKI事件。采用风险比（RR）及95%置信区间（CI）进行荟萃分析。在一项单独的FAERS回顾性药物警戒研究中，使用比例报告比值比（ROR）和信息成分（IC）分析不成比例性。

结果

共纳入79项RCT（50009例患者），ICI与所有级别（RR = 1.37，95%CI：1.14 - 1.65）和高级别AKI（RR = 1.60，95%CI：1.16 - 2.20）风险增加相关。亚组分析结果表明，与ICI相关的AKI的RR在癌症类型、治疗方案（单药治疗或ICI联合治疗）、研究设计（双盲或开放标签）、单个ICI以及发表状态（已发表或未发表）方面无显著差异。FAERS药物警戒数据确定了1918例与ICI治疗相关的AKI病例。ICI与AKI的报告频率过高显著相关（ROR = 2.38，95%CI：2.27 - 2.49；IC = 1.22，95%CI：1.16 - 1.27）。AKI的中位发病时间为48天，77.5%的患者停用了ICI，15.9%的患者死亡。