Signal mining and analysis for adverse events of avatrombopag based on FAERS

Rui XIONG; Jin WANG; Zhen YANG; Yanmei LUO; Hong ZHANG; Yongtao TONG; Xiaodan LAI

doi:10.16016/j.2097-0927.202305092

您当前的位置：

首页 >

文章列表页 >

Signal mining and analysis for adverse events of avatrombopag based on FAERS

Pharmacy | 更新时间：2026-01-09

- Signal mining and analysis for adverse events of avatrombopag based on FAERS
- Journal of Army Medical University Vol. 46, Issue 4, Pages: 369-376(2024)
- 作者机构：
  
  1.400020 重庆，中国人民解放军陆军第九五八医院药剂科
  2.860000 西藏林芝，中国人民解放军陆军第九五六医院药剂科
- 作者简介：
- 基金信息：
  
  the Joint Project of Traditional Chinese Medicine from Chongqing Science and Technology Commission and Chongqing Health Commission(2022MSXM187)
- DOI：10.16016/j.2097-0927.202305092
  CLC： R195.1;R969.3;R973.6
- Received：26 May 2023，
  
  Revised：2023-10-16，
  
  Published：28 February 2024
- 稿件说明：
移动端阅览
Rui XIONG, Jin WANG, Zhen YANG, et al. Signal mining and analysis for adverse events of avatrombopag based on FAERS[J]. Journal of Army Medical University, 2024, 46(4): 369-376.
DOI：

Rui XIONG, Jin WANG, Zhen YANG, et al. Signal mining and analysis for adverse events of avatrombopag based on FAERS[J]. Journal of Army Medical University, 2024, 46(4): 369-376. DOI： 10.16016/j.2097-0927.202305092.

摘要

目的

基于真实世界数据挖掘血小板减少症治疗药物阿伐曲泊帕的药物不良事件(adverse drug events

ADE)信号

为其临床安全应用提供参考。

方法

通过OpenVigil2.1药物警戒平台获取美国食品药品监督管理局不良事件报告系统中2018年5月至2023年3月阿伐曲泊帕的ADE数据

利用《国际医学用语词典》(26.0版)中ADE术语集的首选系统器官分类(system organ class

SOC)和首选术语(preferred term

PT)对ADE信号进行分类和描述

并采用报告比值比(reporting odds ratio

ROR)法和英国药品和保健品管理局综合标准法对ADE数据进行信号检测。

结果

共获取到阿伐曲泊帕相关ADE报告1 879份

累及24个SOC

在PT层级检测到阳性ADE信号28个

其中信号最强的是肾静脉血栓形成、门静脉血栓形成和移植物抗宿主病

报告数最多的是头痛、疲劳和乏力

新发现了8个ADE信号

分别是季节性过敏、背部疾病、肌肉骨骼不适、肠胃气胀、睡眠过度、斑状皮疹、情绪障碍和流涕。

结论

临床应用阿伐曲泊帕时不仅要关注其血栓形成风险

还应密切关注季节性过敏、背部疾病、肌肉骨骼不适、肠胃气胀、睡眠过度、斑状皮疹、情绪障碍和流涕等说明书尚未记载的ADE信号。

Abstract

Objective

To mine the adverse drug events (ADE) signal of avatrombopag

an effective drug for thrombocytopenia treatment

based on real world data in order to provide reference for its clinical safety application.

Methods

The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system (FAERS).The ADE signals were classified and described by the system organ class (SOC) and preferred term (PT) of the ADE terminology set in the Medical Dictionary for Regulatory Activities (MedDRA)

and reporting odds ratio (ROR) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard were used to detect the positive ADE signals.

Results

A total of 1 879 ADE reports related to avatrombopag were obtained

24 SOCs were involved

and 28 positive ADE signals were detected at PT level.Among these signals

the strongest ones were renal vein thrombosis

portal vein thrombosis and graft versus host disease

while the reports accounting for the largest numbers were headache

fatigue and asthenia.There were 8 ADE signals discovered newly

that is

seasonal allergy

back disorder

musculoskeletal discomfort

flatulence

hypersomnia

rash macular

emotional disorder

and rhinorrhoea.

Conclusion

For clinical use of avatrombopag

clinicians should not only concern the risk of thrombosis

but also pay close attention to ADE signals such as seasonal allergy

back disorder

musculoskeletal discomfort

flatulence

hypersomnia

rash macular

emotional disorder

and rhinorrhoea that are not documented in the instructions.

关键词

Keywords

references

FRANCHINI M, VENERI D, LIPPI G. Thrombocytopenia and infections[J]. Expert Rev Hematol, 2017, 10(1): 99-106. DOI: 10.1080/17474086.2017.1271319.

DANESE E, MONTAGNANA M, FAVALORO E J, et al . Drug-induced thrombocytopenia: mechanisms and laboratory diagnostics[J ] . Semin Thromb Hemost, 2020, 46(3): 264-274. DOI: 10.1055/s-0039-1697930.

全军重症医学专业委员会, 中华医学会检验医学分会. 中国成人重症患者血小板减少诊疗专家共识[J]. 解放军医学杂志, 2020, 45(5): 457-474. DOI: 10.11855/j.issn.0577-7402.2020.05.01.

Professional Committee of Military Critical Care Medicine, Laboratory Medicine Branch of Chinese Medical Association. Expert consensus for diagnosis and treatment of thrombocytopenia in adult critical illness in China[J]. Med J Chin PLA, 2020, 45(5): 457-474. DOI: 10.11855/j.issn.0577-7402.2020.05.01.

MAISTRE E, GRUEL Y, LASNE D. Diagnosis and management of heparin-induced thrombocytopenia[J]. Can J Anesth, 2006, 53(S2): S123-S134. DOI: 10.1007/bf03022259.

KUTER D J. The structure, function, and clinical use of the thrombopoietin receptor agonist avatrombopag[J]. Blood Rev, 2022, 53: 100909. DOI: 10.1016/j.blre.2021.100909.

杨育淼. 血小板生成素受体激动剂促进血小板再生在输血医学中的应用与研究进展[J]. 北方药学, 2021, 18(5): 191-192. DOI: 10.3969/j.issn.1672-8351.2021.05.097.

YANG Y M. Application and research progress of thrombopoietin receptor agonist in promoting platelet regeneration in blood transfusion medicine[J]. J North Pharm, 2021, 18(5): 191-192. DOI: 10.3969/j.issn.1672-8351.2021.05.097.

陈灿, 张其坤, 许青. 新型血小板生成素受体激动剂: 阿伐曲泊帕[J]. 中国新药与临床杂志, 2020, 39(11): 652-656. DOI: 10.14109/j.cnki.xyylc.2020.11.03.

CHEN C, ZHANG Q K, XU Q. A novel thrombopoietin receptor agonist: avatrombopag[J]. Chin J New Drugs Clin Remedies, 2020, 39(11): 652-656. DOI: 10.14109/j.cnki.xyylc.2020.11.03.

郝晓静, 马梁明. 阿伐曲泊帕的临床应用进展[J]. 实用医学杂志, 2023, 39(4): 519-524. DOI: 10.3969/j.issn.1006-5725.2023.04.024.

HAO X J, MA L M. Advances in clinical application of avatrombopag[J]. J Pract Med, 2023, 39(4): 519-524. DOI: 10.3969/j.issn.1006-5725.2023.04.024.

AL-SAMKARI H, JIANG D, GERNSHEIMER T, et al . Adults with immune thrombocytopenia who switched to avatrombopag following prior treatment with eltrombopag or romiplostim: a multicentre US study[J ] . Br J Haematol, 2022, 197(3): 359-366. DOI: 10.1111/bjh.18081.

DHODAPKAR M M, SHI X T, RAMACHANDRAN R, et al . Characterization and corroboration of safety signals identified from the US Food and Drug Administration Adverse Event Reporting System, 2008-19: cross sectional study[J ] . Br Med J, 2022, 379: e071752. DOI: 10.1136/bmj-2022-071752.

DUGGIRALA H J, TONNING J M, SMITH E, et al . Use of data mining at the Food and Drug Administration[J ] . J Am Med Inform Assoc, 2015, 23(2): 428-434. DOI: 10.1093/jamia/ocv063.

FANG Q T, HUANG F Q, LIANG J B, et al . Safety of romiplostim and eltrombopag for children with immune thrombocytopenia: a pharmacovigilance study of the FDA adverse event reporting system database[J ] . Expert Opin Drug Saf, 2023, 22(8): 707-714. DOI: 10.1080/14740338.2023.2182288.

BÖHM R, BULIN C, WAETZIG V, et al . Pharmacovigilance-based drug repurposing: the search for inverse signals via OpenVigil identifie s putative drugs against viral respiratory infections[J ] . Br J Clin Pharmacol, 2021, 87(11): 4421-4431. DOI: 10.1111/bcp.14868..

张科, 李波, 宋崟, 等. 基于FAERS数据库的利那洛肽风险信号挖掘[J]. 中国药房, 2022, 33(22): 2758-2761. DOI: 10.6039/j.issn.1001-0408.2022.22.14.

ZHANG K, LI B, SONG Y, et al . Data mining of risk signals for linaclotide based on FAERS database[J ] . China Pharm, 2022, 33(22): 2758-2761. DOI: 10.6039/j.issn.1001-0408.2022.22.14.

KOHLI R, CHATURVEDI S. Epidemiology and clinical manifestations of immune thrombocytopenia[J]. Hamostaseologie, 2019, 39(3): 238-249. DOI: 10.1055/s-0039-1683416.

KARDASHIAN A, SERPER M, TERRAULT N, et al . Health disparities in chronic liver disease[J ] . Hepatology, 2023, 77(4): 1382-1403. DOI: 10.1002/hep.32743.

TRAN T B, DOWNING L, ELMES J B, et al . Avatrombopag for the treatment of immune thrombocytopenia and periprocedural thrombocytopenia associated with chronic liver disease[J ] . J Pharm Pract, 2022: 8971900221125827. DOI: 10.1177/08971900221125827.

TJEPKEMA M, AMINI S, SCHIPPERUS M. Risk of thrombosis with thrombopoietin receptor agonists for ITP patients: a systematic review and meta-analysis[J]. Crit Rev Oncol Hematol, 2022, 171: 103581. DOI: 10.1016/j.critrevonc.2022.103581.

GHANIMA W, COOPER N, RODEGHIERO F, et al . Thrombopoietin receptor agonists: ten years later[J ] . Haematologica, 2019, 104(6): 1112-1123. DOI: 10.3324/haematol.2018.212845.

MARKHAM A. Avatrombopag: a review in thrombocytopenia[J]. Drugs, 2021, 81(16): 1905-1913. DOI: 10.1007/s40265-021-01613-y.

DOMINIETTO A, RAIOLA A M, VAN LINT M T, et al . Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose[J ] . Br J Haematol, 2001, 112(1): 219-227. DOI: 10.1046/j.1365-2141.2001.02468.x.

刘恩伊, 方鹏, 信红亚, 等. 阿伐曲泊帕治疗异基因造血干细胞移植后血小板减少症疗效与安全性的14例真实世界数据评价[J]. 中南大学学报(医学版), 2023, 48(3): 376-385.

LIU E Y, FANG P, XIN H Y, et al . Efficacy and safety of avatrombopag for thrombocytopenia following allogeneic hematopoietic stem cell transplantation: a real-world data evaluation on 14 cases[J ] . J Central South Univ Med Sci, 2023, 48(3): 376-385.

JIANG T T, SU H, LI Y P, et al . Post-marketing safety of immunomodulatory drugs in multiple myeloma: a pharmacovigilance investigation based on the FDA Adverse Event Reporting System[J ] . Front Pharmacol, 2022, 13: 989032. DOI: 10.3389/fphar.2022.989032.

XIONG R, LEI J, PAN S C, et al . Post-marketing safety surveillance of dalfampridine for multiple sclerosis using FDA Adverse Event Reporting System[J ] . Front Pharmacol, 2023, 14: 1226086. DOI: 10.3389/fphar.2023.1226086.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mining inter-transaction association rules from time series microarray data

Related Author

彭斌

李辉智

易东

Related Institution

No data

⁰