Potential drugs for reducing the occurrence of immune checkpoint inhibitor-induced interstitial lung disease: an exploratory study using the JADER and FAERS databases

Background: Immune checkpoint inhibitors (ICIs) play a central role in cancer immunotherapy. However, the occurrence of immune-related adverse events, especially ICI-induced interstitial lung disease (ICI-ILD), is life-threatening and affects the effectiveness of ICI treatment. This study aimed to explore potential drugs to mitigate ICI-ILD occurrence using data from the Japanese Adverse Drug Event Report (JADER) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS [JAPIC AERS]). Research design and methods: We investigated concomitant drugs that reduce ILD associated with four ICIs–nivolumab, pembrolizumab, atezolizumab, and durvalumab–across the JADER and FAERS databases. Subsequently, the identified common concomitant drugs that reduce the occurrence of ICI-ILD were detected and analyzed. Results: We found omega-3 fatty acids, loperamide, and amlodipine as common concomitant drugs that reduced ICI-ILD occurrence in both the JADER and FAERS databases. Omega-3 fatty acids reportedly have many effects in animal models of drug-induced ILD, including their association with ILD in humans and anti-inflammatory effects against ICI-ILD. However, loperamide and amlodipine reportedly have minimal effects against ILD, thereby necessitating further evaluation. Conclusion: Omega-3 fatty acids have emerged as potential agents for reducing ICI-ILD occurrence, as evidenced by findings from two different pharmacovigilance databases.