Komada Fusao, Nakayama Yuko, Takara Kohji
Faculty of Pharmaceutical Sciences, Himeji Dokkyo University.
Yakugaku Zasshi. 2018;138(12):1587-1594. doi: 10.1248/yakushi.18-00094.
The aim of this study has been to investigate the time-to-onset and onset-pattern of drug-induced interstitial lung disease (DILD) after the administration of monoclonal antibodies through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for adalimumab, bevacizumab, cetuximab, denosumab, golimumab, infliximab, nivolumab, panitumumab, pembrolizumab, tocilizumab, and trastuzumab were used to calculate the median time-to-onset of DILD, as well as the Weibull distribution parameters. The median time-to-onset of DILD for pembrolizumab and infliximab was within 1 month. The median time-to-onset of DILD for cetuximab, nivolumab, panitumumab, bevacizumab, golimumab, trastuzumab, and tocilizumab ranged from 1 to 2 months. The median time-to-onset of DILD for denosumab and adalimumab was more than 2 months. Infliximab, trastuzumab and tocilizumab, and denosumab were estimated to fit the early failure type profile of the Weibull distribution parameters. Cetuximab, nivolumab, panitumumab, bevacizumab, golimumab, and adalimumab were estimated to fit the random failure type profile. Pembrolizumab was estimated to fit the wear out failure type profile. Cluster analysis was performed to classify the time-to-onset patterns of DILD. Hierarchical cluster analysis showed 3 clusters. The findings of this study established both the most likely time period and onset-pattern of DILD that can occur in patients after the administration of monoclonal antibody agents.
本研究旨在通过使用日本药品不良反应报告数据库的自发不良反应报告系统，调查单克隆抗体给药后药物性间质性肺病（DILD）的发病时间和发病模式。使用阿达木单抗、贝伐单抗、西妥昔单抗、地诺单抗、戈利木单抗、英夫利昔单抗、纳武单抗、帕尼单抗、派姆单抗、托珠单抗和曲妥珠单抗的DILD数据集来计算DILD的中位发病时间以及威布尔分布参数。派姆单抗和英夫利昔单抗的DILD中位发病时间在1个月内。西妥昔单抗、纳武单抗、帕尼单抗、贝伐单抗、戈利木单抗、曲妥珠单抗和托珠单抗的DILD中位发病时间为1至2个月。地诺单抗和阿达木单抗的DILD中位发病时间超过2个月。英夫利昔单抗、曲妥珠单抗和托珠单抗以及地诺单抗估计符合威布尔分布参数的早期失效类型特征。西妥昔单抗、纳武单抗、帕尼单抗、贝伐单抗、戈利木单抗和阿达木单抗估计符合随机失效类型特征。派姆单抗估计符合耗损失效类型特征。进行聚类分析以对DILD的发病时间模式进行分类。层次聚类分析显示有3个聚类。本研究结果确定了单克隆抗体药物给药后患者可能发生DILD的最可能时间段和发病模式。
