Safety analysis of romiplostim, eltrombopag, and avatrombopag post-market approval: a pharmacovigilance study based on the FDA Adverse Event Reporting System.

Background: Romiplostim, eltrombopag, and avatrombopag, as new-generation thrombopoietin receptor agonists (TPO-RAs), have been widely used in the treatment of immune thrombocytopenia (ITP). Given their similar efficacy, a comprehensive evaluation of their safety is crucial for optimizing treatment choices. This study aims to explore the potential safety issues of three major drugs for treating ITP: romiplostim, eltrombopag, and avatrombopag, thereby providing references and research directions for subsequent high-quality clinical studies.

Methods: We retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2018 to the second quarter of 2023. Using reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multiple gamma poisson shrinkage (MGPS), we mined and analyzed adverse events (AEs) associated with romiplostim, eltrombopag, and avatrombopag. The Designated Medical Event (DME) list from the European Medicines Agency (EMA) was used to screen out the DME of three drugs. Venn analysis was used to screen the specific AEs of each drug.

Results: The study included 2,851 cases of romiplostim, 10,297 cases of eltrombopag, and 973 cases of avatrombopag. Venn analysis revealed nine common AEs across the three drugs. The number of significant specific AEs associated with romiplostim, eltrombopag, and avatrombopag were 58, 98, and 15 respectively. DMEs for romiplostim included autoimmune haemolytic anaemia (ROR = 6.1, n = 3), haemolytic anaemia (ROR = 8.13, n = 7), sudden hearing loss (ROR = 5.24, n = 3), haemolysis (ROR = 3.89, n = 3). DMEs for eltrombopag included hepatic infection (ROR = 9.56, n = 6), granulocytopenia (ROR = 2.91, n = 4), autoimmune haemolytic anaemia (ROR = 3.03, n = 5), haemolytic anaemia (ROR = 3.46, n = 10), haemolysis (ROR = 4.65, n = 12), hepatic failure (ROR = 2.51, n = 23). Not a single DME was found for avatrombopag.

Conclusion: This study indicates that eltrombopag manifests significant safety signals within the hepatic system. This implies that monitoring liver function during treatment is advisable. Avatrombopag shows relatively lower hepatotoxicity signals; however, further large-scale studies are needed to validate these observations. Moreover, both romiplostim and eltrombopag therapies may be linked to a risk of sudden hearing loss or deafness, which merits clinical attention. These findings offer crucial safety references for clinical drug use. Nevertheless, the causal relationship between the drugs and AEs necessitates further in-depth investigation.