基于FAERS数据库的枸橼酸伊沙佐米胶囊安全信号挖掘研究

doi:10.19803/j.1672-8629.20230408

摘要/Abstract

摘要： 目的挖掘分析枸橼酸伊沙佐米胶囊（简称“伊沙佐米”）上市后潜在的不良事件（AE）风险信号,为其临床合理使用提供参考。方法提取美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库中伊沙佐米从2015年11月上市到2023年3月31日的AE报告,并对数据进行清洗去重和标准化。采用报告比值法（ROR）和贝叶斯置信度递进神经网络法（BCPNN）进行AE信号挖掘。结果在数据库中以伊沙佐米为首要怀疑的AE报告共14 156例。经ROR法和BCPNN法进行检测筛选,获得204个有效首选术语（PT）信号,累及17个系统-器官分类（SOC）。与说明书进行比对发现,说明书未记载的PT信号有156个,新发比较严重AE信号为死亡、心血管系统、肾脏及泌尿系统等,临床需给予高度关注。结论对伊沙佐米真实世界的不良事件进行挖掘,提示临床需慎重评估伊沙佐米AE危险因素,加强用药监护,保障患者用药安全。

关键词: 枸橼酸伊沙佐米胶囊, 蛋白酶体抑制剂, 信号挖掘, FDA不良事件报告系统, 药品不良事件

Abstract: Objective To mine and analyse the potential adverse event (AE) risk signals of ixazomib citrate capsules post-marketing to provide a reference for its rational clinical application. Methods Extract the FAERS database of AE reported for Ixazomib citrate capsules from marketing (November 2015) to March 31,2023, data cleaning and de-duplication and standardization. Signal mining was performed using the Reported Ratio (ROR) and Bayesian Confidence Progressive Neural Network (BCPNN) methods. Results A total of 14 156 AE were reported in the database with Ixazomib citrate capsules as the primary suspect. Mining by ROR and BCPNN methods resulted in 204 potential positive PTs, involving 17 SOC. Among them, there are 156 PT signals that are not specified in drug instruction, including the new and relatively serious AE such as death, cardiovascular system and renal-urinary system, which require high clinical attention. Conclusion Mining the real-world adverse events of ixazomib citrate capsules suggests that the clinical caution in evaluating its AE risk factors and strengthening the medication monitoring to ensure the safety of the medication for the patients.

Key words: ixazomib citrate capsules, proteasome inhibitors, signal mining, FDA adverse event reporting system (FAERS), adverse drug event

中图分类号:

郝晓慧, 张萍, 武璐璐, 王丽华. 基于FAERS数据库的枸橼酸伊沙佐米胶囊安全信号挖掘研究[J]. 中国药物警戒, 2023, 20(12): 1427-1431.

HAO Xiaohui, ZHANG Ping, WU Lulu, WANG Lihua. Mining and analysis of ixazomib citrate capsules safety signals based on FAERS database[J]. Chinese Journal of Pharmacovigilance, 2023, 20(12): 1427-1431.

参考文献

[1] GUPTA N, HANLEY MJ, XIA C, et al.Clinical pharmacology of ixazomib: the first oral proteasome inhibitor[J]. Clin Pharmacokinet, 2019, 58(4): 431-449.
[2] XU Y, QIU LG.Application of proteasome inhibitors in the treatment of multiple myeloma[J]. Chinese Journal of Clinical Oncology(中国肿瘤临床), 2022, 49(20): 1028-1032.
[3] VAN DE DONK N, PAWLYN C, YONG KL. Multiple myeloma[J]. Lancet, 2021, 397(10272): 410-427.
[4] DIMOPOULOS MA, MOREAU P, TERPOS E, et al.Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2021, 32(3): 309-322.
[5] Chinese Hematology Association, Chinese Society of Hematology.Guidelines for the diagnosis and management of multiple myeloma in China (2022 revision)[J]. China Journal of Internal Medicine(中华内科杂志)2022, 61(5): 480-487.
[6] DIMOPOULOS MA, RAJKUMAR S V, LONIAL S, et al.Interim analyses of overall survival (OS) from the TOURMALINE MM3 & MM4 studies of ixazomib maintenance following primary therapy in multiple myeloma (MM)[J]. Blood, 2021, 138(Supplement 1): 1656-1656.
[7] HU Y, GONG J, ZHANG L, et al.Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system[J]. Int Immunopharmacol, 2020, 84: 106601.
[8] CHOW JW, YAN MM, ZHAO H, et al.Skin cancer signal associated with phosphodiesterase inhibitors: gaining insight through the FDA pharmacovigilance database[J]. Expert Opin Drug Saf, 2023, 22(5): 433-441.
[9] NGUYEN DD, MARCHESE M, CONE EB, et al.Investigation of suicidality and psychological adverse events in patients treated with finasteride[J]. JAMA Dermatol, 2021, 157(1): 35-42.
[10] BATE A.Bayesian confidence propagation neural network[J]. Drug Saf, 2007, 30(7): 623-625.
[11] TAN JT.Data mining and analysis of adverse reactions of ACEI drugs based on FAERS database[D]. Chongqing: Chongqing Medical University, 2021.
[12] CALLANDER NS, BALJEVIC M, ADEKOLA K, et al.NCCN guidelines^® insights: multiple myeloma, version 3.2022: featured updates to the NCCN guidelines[J]. Journal of the National Comprehensive Cancer Network, 2022, 20(1): 8-19.
[13] SUNG H, FERLAY J, SIEGEL RL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209-49.
[14] WU XF, WU B, YANG CS, et al.Data mining and adverse event signals of bortezomib based on FAERS database[J]. Anti-Tumor Pharmacy(肿瘤药学), 2022, 12(1): 82-91.
[15] MOREAU P, MASSZI T, GRZASKO N, et al.Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma[J]. N Engl J Med, 2016, 374(17): 1621-1634.
[16] FACON T, VENNER CP, BAHLIS NJ, et al.Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma[J]. Blood, 2021, 137(26): 3616-3628.
[17] XIONG Q, REN SH, LI XM.Efficacy and safety of therapy with ixazomib in patients with multiple myeloma: a meta-analysis[J]. Journal of Clinical Transfusion and Laboratory Medicine(临床输血与检验), 2023, 25(2): 243-249.
[18] JOUNI H, AUBRY MC, LACY MQ, et al.Ixazomib cardiotoxicity: a possible class effect of proteasome inhibitors[J]. Am J Hematol, 2017, 92(2): 220-221.
[19] WU P, OREN O, GERTZ MA, et al.Proteasome inhibitor-related cardiotoxicity: mechanisms, diagnosis, and management[J]. Curr Oncol Rep, 2020, 22(7): 66.
[20] RAJE NS, ANAISSIE E, KUMAR SK, et al.Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the international Myeloma Working Group[J]. Lancet Haematol, 2022, 9(2): e143-e161.
[21] GENEST DS, PATRIQUIN CJ, LICHT C, et al.Renal thrombotic microangiopathy: a review[J]. Am J Kidney Dis, 2023, 81(5): 591-605.
[22] MICHAEL M, BAGGA A, SARTAIN SE, et al.Haemolytic uraemic syndrome[J]. Lancet, 2022, 400(10364): 1722-1740.
[23] MAZZIERLI T, ALLEGRETTA F, MAFFINI E, et al.Drug-induced thrombotic microangiopathy: an updated review of causative drugs, pathophysiology, and management[J]. Front Pharmacol, 2022, 13: 1088031.
[24] NGUYEN MN, NAYERNAMA A, JONES SC, et al.Proteasome inhibitor-associated thrombotic microangiopathy: a review of cases reported to the FDA adverse event reporting system and published in the literature[J]. Am J Hematol, 2020, 95(9): e218-e222.