Abstract
Ministry of Health, Labour and Welfare has been promoting predictive and preventive drug safety measures. Drug-induced interstitial pneumonia (DILD) is a severe adverse drug reaction that is frequently reported in Japanese. Among various types of DILD, the diffuse alveolar damage (DAD) type is particularly important to identify in early stage and initiate appropriate treatment, because it may cause death and sequelae. We collaborated with four university hospitals in Japan to search biomarkers of DILD.
As a result, we found stratifin as a serum DAD marker that is elevated in the acute phase and decreased in the recovery phase, and was useful for discriminating DAD from other DILD types (such as organizing pneumonia and non-specific interstitial pneumonia) (Arakawa N. et al., Nat Commun. 2022;13:5854). These findings were successfully replicated in another cohort and was also useful for discriminating the DAD type of DILD from other related diseases (bacterial pneumonia, lung cancer, COPD, etc.). Note that employed analytical method was constructed and validated for the necessary parameters. Furthermore, the immunohistochemical analysis of autopsy samples revealed stratifin expression in the lung epithelium of DAD patients, and the results using cultured cells suggested p53- and apoptosis-dependent release of stratifin to the extracellular space. These results strongly suggested that stratifin is a useful DILD marker for DAD type. Separately, lysophosphatidylcholine was also found as a biomarker that could discriminate between DILD and idiopathic ILD (Saito K. et al., Sci Rep. 2022 ;12:19819). Based on these results, we received the pharmacogenomics and biomarker consultation of PMDA.
In our presentation, after introducing the above examples, we would like to propose an appropriate strategy for establishing safety biomarkers.
