Zhang Jing, Qiu Ting, Zhou Yiting, Wu Shengjie, Chen Enguo
Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Pulmonary and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Expert Opin Drug Saf. 2023 Jul-Dec;22(9):849-856. doi: 10.1080/14740338.2023.2193392. Epub 2023 Apr 7.
Interstitial lung disease (ILD) was a relatively common cause of drug-induced mortality. However, the safety profile of the whole TKIs induced ILD was largely unknown.
The reported cases of ILD associated with TKIs were downloaded from the FDA adverse event reporting system (FAERS) database between 1 January 2004 and 30 April 2022 to detect ILD signals by disproportionality analysis. Furthermore, the fatality rate and time to onset (TTO) of various TKIs were also calculated.
The median age of total 2999 reported cases was 67. The largest reported cases came from osimertinib (n = 736, 24.5%). However, gefitinib had the highest ROR of 12.47 (11.4, 13.64) and IC of 3.53 (3.23, 3.86), means the strongest association with ILD. Trametinib, vemurafenib, larotectinib, selpercatinib, and cabozantinib did not show ILD signal. The median age of dead cases was 72 (Q1:62, Q3:83), and 53.02% (n = 579) were female and 41.11% (n = 449) were male. MET group showed the highest fatality rate of 55.17% with the shortest median TTO of 21 days (Q1: 8.5, Q3: 35.5).
TKIs were significantly associated with ILD. More attention should be paid to female, older, MET group with shorter TTO, as their prognosis might be worse.
间质性肺疾病（ILD）是药物诱导死亡的一个相对常见原因。然而，整个酪氨酸激酶抑制剂（TKIs）诱导的ILD的安全性概况在很大程度上尚不清楚。
2004年1月1日至2022年4月30日期间，从美国食品药品监督管理局不良事件报告系统（FAERS）数据库中下载与TKIs相关的ILD报告病例，通过不成比例分析检测ILD信号。此外，还计算了各种TKIs的死亡率和发病时间（TTO）。
2999例报告病例的中位年龄为67岁。报告病例数最多的来自奥希替尼（n = 736，24.5%）。然而，吉非替尼的报告比值比（ROR）最高，为12.47（11.4，13.64），信息成分（IC）为3.53（3.23，3.86），这意味着与ILD的关联最强。曲美替尼、维莫非尼、拉罗替尼、塞尔帕替尼和卡博替尼未显示出ILD信号。死亡病例的中位年龄为72岁（第一四分位数：62，第三四分位数：83），53.02%（n = 579）为女性，41.11%（n = 449）为男性。MET组的死亡率最高，为55.17%，中位TTO最短，为21天（第一四分位数：8.5，第三四分位数：35.5）。
TKIs与ILD显著相关。应更多关注女性、老年、TTO较短的MET组患者，因为他们的预后可能更差。
