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
Objective 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.Design Retrospective pharmacovigilance analysis of the Food...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-08-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/8/e099153.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850032586528653312 |
|---|---|
| author | Zheng Wang Xiaojia Huang Yanqin Huang Xinhang Liao Changze Zhang Liangping Yu |
| author_facet | Zheng Wang Xiaojia Huang Yanqin Huang Xinhang Liao Changze Zhang Liangping Yu |
| author_sort | Zheng Wang |
| collection | DOAJ |
| description | Objective 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.Design Retrospective pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.Setting Both FAERS and JADER were searched from January 2004 to March 2025.Main outcome measures 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.Results 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.Conclusions 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. |
| format | Article |
| id | doaj-art-7d323f28c0bc457990a0c45f467458dc |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-7d323f28c0bc457990a0c45f467458dc2025-08-20T02:58:34ZengBMJ Publishing GroupBMJ Open2044-60552025-08-0115810.1136/bmjopen-2025-099153Relationship between thromboembolic events and thrombopoietin receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System and the Japanese Adverse Drug Event ReportZheng Wang0Xiaojia Huang1Yanqin Huang2Xinhang Liao3Changze Zhang4Liangping Yu5Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Pharmacy, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, Fujian, ChinaDepartment of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaObjective 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.Design Retrospective pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.Setting Both FAERS and JADER were searched from January 2004 to March 2025.Main outcome measures 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.Results 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.Conclusions 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.https://bmjopen.bmj.com/content/15/8/e099153.full |
| spellingShingle | Zheng Wang Xiaojia Huang Yanqin Huang Xinhang Liao Changze Zhang Liangping Yu 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 BMJ Open |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/15/8/e099153.full |
| work_keys_str_mv | AT zhengwang relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport AT xiaojiahuang relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport AT yanqinhuang relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport AT xinhangliao relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport AT changzezhang relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport AT liangpingyu relationshipbetweenthromboemboliceventsandthrombopoietinreceptoragonistsapharmacovigilanceanalysisofthefdaadverseeventreportingsystemandthejapaneseadversedrugeventreport |