Graduate School of Clinical Pharmacy, Shujitsu University.
Department of Pharmacy, NHO Okayama Medical Center.
Biol Pharm Bull. 2024;47(7):1296-1300. doi: 10.1248/bpb.b24-00130.
Interstitial lung disease (ILD) is a serious adverse event caused by the administration of immune checkpoint inhibitors (ICIs). However, only few large-scale studies have explored the association among ICI use, underlying cancer type, and ILD complications. This study aimed to analyze the association between the primary cancer type and ICI-induced ILD in a cross-sectional manner using the Japanese Adverse Drug Event Report (JADER) database. Nivolumab and pembrolizumab (anti-programmed cell death 1 (PD-1) antibodies) and durvalumab, avelumab, and atezolizumab (anti-programmed cell death ligand 1 (PD-L1) antibodies) were included as ICIs in this study. Adverse events were identified based on the preferred terms of Medical Dictionary for Regulatory Activities (MedDRA) version 27.0/J listed in the Standardized MedDRA Queries (SMQ) "interstitial lung disease." The reporting odds ratio was calculated to detect the association between ICI use and ILD complications, and a signal was detected if the lower limit of the 95% confidence interval exceeded 1. In the analysis of all cancer types, a signal was detected for all ICIs except avelumab. An association between ICI and ILD was detected for all cancer types with nivolumab. However, pembrolizumab exhibited a signal only in colorectal cancer. In contrast, anti-PD-L1 antibodies displayed signals in five cancer types, excluding head and neck cancer, which was not reported in JADER. Among these cancer types, atezolizumab exhibited a signal only in breast cancer. The results of this study will help guide the safe use of ICIs based on the underlying cancer type in terms of ILD complications.
间质性肺病 (ILD) 是免疫检查点抑制剂 (ICI) 给药引起的严重不良事件。然而,仅有少数大规模研究探讨了 ICI 使用、基础癌症类型和 ILD 并发症之间的关系。本研究旨在使用日本不良事件报告数据库 (JADER) 以横断面方式分析主要癌症类型与 ICI 诱导的 ILD 之间的关联。本研究将纳武单抗和帕博利珠单抗(抗程序性细胞死亡 1 (PD-1) 抗体)以及度伐鲁单抗、avelumab 和阿替利珠单抗(抗程序性细胞死亡配体 1 (PD-L1) 抗体)作为 ICI 纳入研究。根据标准 MedDRA 查询 (SMQ) 中列出的 MedDRA 监管活动首选术语 (MedDRA) 版本 27.0/J 的“间质性肺病”确定不良事件。计算报告比值比以检测 ICI 使用与 ILD 并发症之间的关联,如果 95%置信区间的下限超过 1,则检测到信号。在所有癌症类型的分析中,除了 avelumab 之外,所有 ICI 均检测到信号。纳武单抗与所有癌症类型的 ICI 和 ILD 之间均存在关联。然而,pembrolizumab 仅在结直肠癌中显示出信号。相比之下,抗 PD-L1 抗体在五种癌症类型中显示出信号,除了在 JADER 中未报告的头颈部癌症。在这些癌症类型中,阿替利珠单抗仅在乳腺癌中显示出信号。本研究的结果将有助于根据 ILD 并发症,指导基于基础癌症类型的 ICI 安全使用。