Risk of Drug-Induced Interstitial Lung Disease in Korean Patients With Lung Cancer: A Nested Case-Control Study

OBJECTIVES: Drug-induced interstitial lung disease (DIILD) is a serious adverse event (AE) caused by exposure to drugs, leading to inflammation and possibly interstitial fibrosis. This study aims to investigate the risk of DIILD according to the category of anticancer drugs in Korean patients with lung cancer (LC).

METHODS: Using the entire patients’ claims database provided by the Korean Health Insurance Review and Assessment from 2017 to 2021, patients newly diagnosed with LC were defined as a cohort. A nested case-control study design was employed, and patients diagnosed with DIILD within the cohort were identified as the case group. The control group was matched to each case on age, sex, antineoplastic agents’ initiation date. We explored characteristics of DIILD patients and the association between drug category and DIILD development using conditional logistic regression.

RESULTS: Of 43,697 patients with LC aged 19 or greater, 936 (2.14%) experienced DIILD. Approximately 86% of DIILD patients was aged 60 year or over and 81% were male. The mean(±SD) CCI score was 4.99±3.01. They had a medical history of chronic obstructive pulmonary disease (57%) followed by dyslipidemia (42%), hypertension (38%), and diabetes (31%). Immune checkpoint inhibitors and multikinase inhibitors were associated with an increased risk of DIILD, with odds ratios (OR) 1.65 (95% CI: 1.36 to 2.02) and 1.59 (95% CI: 1.12 to 2.26), respectively. However, epidermal growth factor receptor inhibitors were associated with a reduced risk of DIILD (OR: 0.63, 95% CI: 0.51 to 0.79). There was no significant association with cytotoxic agents (OR: 0.96, 95% CI: 0.83 to 1.12).

CONCLUSIONS: In this retrospective study, the incidence of DIILD differs significantly by the category of anticancer agents. Our findings underscore the importance of careful consideration when selecting and administering specific antineoplastic agents. However, further long-term studies are required to identify the risk factors for DIILD.