A Real-World Pharmacovigilance Analysis for Demethylation Drug: Findings from the FDA Adverse Event Reporting Database.

Abstract

Introduction: The real-world safety profiles of the demethylating agents azacitidine and decitabine remain inadequately characterized despite their widespread clinical use. Both drugs are extensively employed for the treatment of hematologic malignancies such as myelodysplastic syndromes and acute myeloid leukemia. This study aimed to evaluate their adverse event profiles by leveraging data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Methods: All adverse drug event (ADE) data related to azacitidine and decitabine were collected from the FAERS database from its inception through the second quarter of 2024 (Q2). After standardizing the data, four disproportionality methods were applied to evaluate the association between azacitidine, decitabine, and ADEs. The Weibull shape parameter was used to analyze the time-to-onset curves.

Results: Among the 15,538 ADEs where azacitidine was the primary suspect drug, a total of 439 preferred terms (PTs) and 2 system organ classes (SOCs) showed significant disproportionality across all four algorithms. These SOCs included infections and infestations (n = 7,328, ROR 3.78) and blood and lymphatic system disorders (n = 5,613, ROR 8.92). Compared with the azacitidine label, 52 previously unreported ADEs were identified at the PT level. Among the 3,064 ADEs where decitabine was the primary suspect drug, a total of 200 PTs and two SOCs exhibited significant disproportionality across all four algorithms. These SOCs included blood and lymphatic system disorders (n = 1,284, ROR 6.53) and surgical and medical procedures (n = 571, ROR 3.41). Compared with the decitabine label, 29 previously unreported ADEs were identified at the PT level. Furthermore, the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm revealed that the highest IC025 values for both azacitidine and decitabine were concentrated in SOCs related to benign, malignant, and unspecified tumors.

Conclusion: In summary, using the FAERS database, we compared the real-world safety profiles of two demethylating agents, azacitidine and decitabine. The results indicate that adverse drug reactions related to these two agents are concentrated in the hematologic, respiratory, circulatory, and digestive systems, as well as in neoplasms of unspecified nature, warranting close clinical attention.