Abstract
Background:Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of PD-1, PD-L1 and CTLA-4 inhibitors by mining the real-world data reported in two international pharmacovigilance databases.Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014, to December 31, 2019, and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining methods were used to detect the signal of five fatal toxic effects caused by ICIs.Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADEwasipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Elderly patients and male patients were more likely to develop ICIs-related myocarditis.The results of signal detection showed that the risk of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP)method was the strongest.Conclusion:The findings of this study showed the risk of developing myocarditis and other fatal ADRs when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.
Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors
