The risk and economic burden of interstitial lung disease in patients with non-small cell lung cancer treated with immune checkpoint inhibitors and targeted therapies

Despite improved survival with targeted therapies and immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), evidence regarding the risk and economic burden of drug-induced interstitial lung disease (DI-ILD)—a potentially fatal adverse event—remains limited. We evaluated drug- and generation-specific risks of DI-ILD and its associated economic burden. Using the Health Insurance Review and Assessment Service (HIRA) claims database (January 1, 2012-May 31, 2023), we identified patients treated with ICIs, epidermal growth factor receptor inhibitors (EGFRis), or anaplastic lymphoma kinase inhibitors (ALKis). Incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) for ILD were estimated using stabilized generalized propensity scores weighting and Cox proportional hazards models. After 1:4 propensity score matching, healthcare costs and resource utilization during ILD treatment period were compared between patients with and without ILD. Among 12,744 ICI users, 44,689 EGFR and 5,655 ALK prescription records, 111, 178, and 33 cases of ILD were identified, respectively. Compared with nivolumab, pembrolizumab (HR, 2.14; 95% CI, 1.12–4.11) and atezolizumab (HR, 1.80; 95% CI, 0.96–3.38) showed higher ILD risk. First- (HR, 0.67; 95% CI, 0.44-1.00) and third-generation EGFRis (HR, 0.45; 95% CI, 0.22–0.89) had significantly lower risks than second-generation EGFRis. Compared with third-generation ALKis, first-generation (HR, 0.15; 95% CI, 0.03–0.70) and second-generation ALKis (HR, 0.20; 95% CI, 0.04–0.89) showed significantly lower risks of ILD. ILD was associated with higher healthcare costs and utilization, including hospitalization costs (2.11–5.24 times), infection and respiratory medication costs (2.72–13.88 times), hospitalization admissions (1.69–3.84 times), length of stay (1.66–2.57 times), and emergency room visits (1.21–5.58 times). Given the substantial economic burden DI-ILD imposes, understanding differential risks of DI-ILD across treatment options could inform treatment selection and enable more timely management.