A post-marketing disproportionality analysis of the safety of ribociclib based on the FDA Adverse Event Reporting System.

Background: Although there are reports of adverse events (AEs) of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the safety of ribociclib alone has not yet been comprehensively evaluated in real-world clinical practice.

Objectives: To investigate the overall real-world safety profile of ribociclib by mining data from the FDA Adverse Event Reporting System (FAERS).

Design: A retrospective disproportionality analysis was conducted based on the FAERS database.

Methods: We processed reports from the first quarter of 2017 to the second quarter of 2023 and applied disproportionality analysis using four different methods: reporting odds ratio, Medicines and Healthcare Products Regulatory Agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.

Results: A total of 12,885 AE reports of ribociclib as the primary suspect were enrolled. 48.81% of AEs occur within 60 days of ribociclib administration. Blood and lymphatic system disorders and abnormalities in investigation at the system organ class level showed statistically significant signals in all four methods. Nausea ( = 1426), neutropenia ( = 940), vomiting ( = 863), white blood cell count decreased ( = 812), and alopecia ( = 536) turned out to be the five most frequent AEs at the preferred term level. Twenty-eight AEs undiscovered in the label were newly identified. Neutropenia, as a widely recognized AE, was observed to potentially result in more serious outcomes than previously anticipated ( < 0.001).

Conclusion: This study utilized the FAERS database to analyze real-world AE signals associated with ribociclib following its market approval. We characterized the clinical profiles of reported AEs and found some significant signals consistent with previous clinical trials. In addition, several AEs not included in the drug label or exhibiting unexpected severity were detected. These findings provide valuable insights for clinicians and highlight directions for further causality-focused research to validate the observed results.