Relationship between thromboembolic events and thrombopoietin receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System and the Japanese Adverse Drug Event Report.

Abstract

Thrombopoietin receptor agonists (TPO-RAs) are widely used in thrombocytopenia, yet their association with thromboembolic events (TEEs) remains concerning. This study aimed to assess the real-world TEE risk associated with TPO-RAs. Retrospective pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases. Both FAERS and JADER were searched from January 2004 to March 2025. Disproportionality analyses were performed using reporting OR (ROR), proportional reporting ratio (PRR), informational component (IC) and empirical Bayesian geometric mean (EBGM) to identify potential safety signals. 4005 TEE from FAERS and 569 from JADER were analysed. Venous TEE showed higher prevalence and signal intensity (FAERS: n=1489, ROR 4.19, PRR 4.14, EBGM05 3.94, IC025 0.37; JADER: n=269, ROR 15.95, PRR 14.27, EBGM05 12.56, IC025 2.14). Lusutrombopag had the strongest TEE signal (FAERS: n=7, ROR 8.80, PRR 7.77, EBGM05 4.00, IC025 1.25; JADER: n=41, ROR 38.02, PRR 16.94, EBGM05 11.45, IC025 2.38). FAERS identified 49 positive signals, while JADER identified 30, with 20 signals overlapping. Subgroup analysis indicated males had higher arterial TEE risk with TPO-RAs, while females had higher venous TEE risk in both FAERS and JADER. In FAERS, elderly (≥60 years) showed elevated arterial TEE risk with TPO-RAs and romiplostim, while non-elderly had higher venous TEE risk with avatrombopag and eltrombopag. The study provided real-world evidence of TEE associated with TPO-RAs, highlighting a strong link despite variations in signal values and regional reporting practices. Findings underscore ongoing clinical safety surveillance for TPO-RAs.