A comparative analysis of the safety profiles between inclisiran and other PCSK9 inhibitors from real-world evidence – what have we learned recently?

BACKGROUND: Inclisiran is a novel inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). This study aimed to explore its safety profiles. RESEARCH DESIGN AND METHODS: Reports from FDA Adverse Event Reporting System were collected and analyzed from January 2021 to September 2023. The ROR method was employed to detect safety signals. Comparative analysis was conducted at levels of SOCs, HLGTs, and PTs with other PCSK9 inhibitors. RESULTS: A total of 136 safety signals were identified, and the majority were novel. In comparison with other PCSK9 inhibitors, inclisiran had a greater number of adverse drug events in 'Gastrointestinal disorders' and 'Infections and infestations.' 'Gastrointestinal symptoms and motility' and 'respiratory and urinary tract infections' are the principal causes for the aforementioned safety issues. Nevertheless, inclisiran demonstrates potential advantages in terms of safety, particularly in 'Eye disorders,' 'Skin and subcutaneous tissue disorders' and 'General disorders and administration site condition.' CONCLUSION: Due to distinctive pharmacological mechanism of action, the safety issues of inclisiran merit meticulous consideration. There are some safety profile tendencies that differ from other PCSK9 inhibitors. Therefore, special attention should be paid to its administration in high-risk populations. Additionally, some results remain uncertain, requiring further verification.