基于FAERS数据库的enfortumab vedotin的药物警戒评价

doi:10.5246/jcps.2023.02.011

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (2): 130-137.DOI: 10.5246/jcps.2023.02.011

• 【药事管理与临床药学专栏】 • 上一篇下一篇

基于FAERS数据库的enfortumab vedotin的药物警戒评价

杨辉¹^,^#, 王浩舟²^,^#, 安卓玲¹^,^*()

1. 首都医科大学附属北京朝阳医院药事部, 北京 100020
2. 首都医科大学附属北京朝阳医院泌尿外科, 北京 100020

收稿日期:2022-09-26 修回日期:2022-10-29 接受日期:2022-11-05 出版日期:2023-02-28 发布日期:2023-02-28
通讯作者: 安卓玲
作者简介:
+ Tel./Fax:: +86-10-85231077, E-mail: anzhuoling@163.com

Pharmacovigilance evaluation of enfortumab vedotin using the FDA Adverse Event Reporting System

Hui Yang¹^,^#, Haozhou Wang²^,^#, Zhuoling An¹^,^*()

1 Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
2 Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

Received:2022-09-26 Revised:2022-10-29 Accepted:2022-11-05 Online:2023-02-28 Published:2023-02-28
Contact: Zhuoling An
About author:
# The two authors contributed equally to this work.

摘要/Abstract

摘要：

因为enfortumab vedotin (EV)上市应用的数据较少, 对于全面评估此药的安全性仍是挑战。因此, 本研究基于美国FDA不良事件报告系统总结EV相关不良反应, 并分析潜在的不良事件信号。提取2004年1月1日到2021年11月4日的不良反应报告。不良事件人群特征采用描述性分析, 不同组间比较采用卡方分析。采用报告比值比法(ROR)和比例报告比值法(PRR)对上述不良事件报告进行数据挖掘与分析。本研究共纳入409份不良事件报告, 在死亡病例和非死亡病例间性别、年龄、报告年限、报告地区无显著性差异。潜在的严重不良事件包括肾损伤(IC₀₂₅ 1.25, ROR₀₂₅ 2.82, 弱信号), 泌尿系统感染(IC₀₂₅ 0.28, ROR₀₂₅ 1.44, 弱信号)和发热性中性粒细胞减少(IC₀₂₅ 0.62, ROR₀₂₅ 2.22, 弱信号)。危及生命的不良反应事件包括史蒂文斯-约翰逊综合征(IC₀₂₅ 2.88, ROR₀₂₅ 15.20, 中等信号)、表皮坏死松解症(IC₀₂₅ 2.52, ROR₀₂₅ 15.52, 中等信号)、急性肾损伤(IC₀₂₅ 0.47, ROR₀₂₅ 1.67, 弱信号)和多器官衰竭(IC₀₂₅ 0.03, ROR₀₂₅ 2.23, 弱信号)。在使用EV时, 应警惕EV相关的尿路感染和发热性中性粒细胞减少, 同时也应警惕危及生命的不良反应事件如史蒂文斯-约翰逊综合征、表皮坏死松解症、急性肾损伤和多器官衰竭。

关键词: Enfortumab vedotin, FAERS, 药物经济评价, 真实世界分析

Abstract:

There is still a challenge to comprehensively assess the safety of enfortumab vedotin (EV) in the real world with limited data. In the present study, we aimed to characterize the main features of EV-related adverse drug reactions (ADRs) and identify any potential safety signal using the US Food and Drug Administration Adverse Event Reporting System (FAERS). The evaluation included FAERS reports from Jan. 1, 2004 to Nov. 4, 2021. Standard descriptive statistics were used to summarize the study population characteristics. The chi-square tests for categorical variables were used for between-group comparisons. The disproportionality analysis was conducted by using Bayesian confidence propagation neural network of information component (IC) and reporting odds ratio (ROR). 409 EV-related reports were identified. No significant differences were found in gender, age, reporting year, or reporting region between fatal and non-fatal cases. Potentially serious ADRs were found, including kidney injury (IC₀₂₅ 1.25, ROR₀₂₅2.82, weak signal), urinary tract infection (IC₀₂₅ 0.28, ROR₀₂₅1.44, weak signal), and febrile neutropenia (IC₀₂₅ 0.62, ROR₀₂₅2.22, weak signal). Life-threatening ADRs, including Stevens-Johnson syndrome (SJS, IC₀₂₅ 2.88, ROR₀₂₅15.20, middle signal), toxic epidermal necrolysis (TEN, IC₀₂₅ 2.52, ROR₀₂₅15.52, middle signal), acute kidney injury (IC₀₂₅ 0.47, ROR₀₂₅1.67, weak signal), and multiple organ dysfunction syndrome (MODS, IC₀₂₅ 0.03, ROR₀₂₅2.23, weak signal), were also detected to be significantly associated with EV use. EV could lead to kidney injury, urinary tract infection, and febrile neutropenia. Life-threatening ADRs, including SJS, TEN, acute kidney injury, and MODS, were also significantly associated with EV use.

Key words: Enfortumab vedotin, FAERS, Pharmacovigilance evaluation, Real-word study

Supporting:

杨辉, 王浩舟, 安卓玲. 基于FAERS数据库的enfortumab vedotin的药物警戒评价[J]. 中国药学(英文版), 2023, 32(2): 130-137.

Hui Yang, Haozhou Wang, Zhuoling An. Pharmacovigilance evaluation of enfortumab vedotin using the FDA Adverse Event Reporting System[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(2): 130-137.

图/表 5

Table 1. Characteristics of patients with EV-associated ADRs sourced from the FAERS database (from Jan. 1, 2017 to Nov. 4, 2021).

Table 2. Signal values associated with EV.

Table 3. Signal values of kidney injury associated with EV.

Table 4. Signal values of blood and lymphatic system disorders associated with EV.

Table 5. Signal values of life-threatening ADRs associated with EV.

参考文献 20

[1]	Viscuse, P.V.; Marques-Piubelli, M.L.; Heberton, M.M.; Parra, E.R.; Shah, A.Y.; Siefker-Radtke, A.; Gao, J.J.; Goswami, S.; Ivan, D.; Curry, J.L.; Campbell, M.T. Case report: enfortumab vedotin for metastatic urothelial carcinoma: a case series on the clinical and histopathologic spectrum of adverse cutaneous reactions from fatal stevens-Johnson syndrome/toxic epidermal necrolysis to dermal hypersensitivity reaction. Front. Oncol. 2021, 11, 621591.
[2]	Sidaway, P. Sacituzumab govitecan is safe and effective. Nat. Rev. Clin. Oncol. 2021, 18, 400.
[3]	Hanna, K.S. Enfortumab vedotin to treat urothelial carcinoma. Drugs Today (Barc). 2020, 56, 329–335.
[4]	Criscitiello, C.; Morganti, S.; Curigliano, G. Antibody-drug conjugates in solid tumors: a look into novel targets. J. Hematol. Oncol. 2021, 14, 20.
[5]	Alt, M.; Stecca, C.; Tobin, S.; Jiang, D.M.; Sridhar, S.S. Enfortumab vedotin in urothelial cancer. Ther. Adv. Urol. 2020, 12, 1756287220980192.
[6]	Powles, T.; Rosenberg, J.E.; Sonpavde, G.P.; Loriot, Y.; Durán, I.; Lee, J.L.; Matsubara, N.; Vulsteke, C.; Castellano, D.; Wu, C.; Campbell, M.; Matsangou, M.; Petrylak, D.P. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N. Engl. J. Med. 2021, 384, 1125–1135.
[7]	Yu, E.Y.; Petrylak, D.P.; O'Donnell, P.H.; Lee, J.L.; van der Heijden, M.S.; Loriot, Y.; Stein, M.N.; Necchi, A.; Kojima, T.; Harrison, M.R.; Park, S.H.; Quinn, D.I.; Heath, E.I.; Rosenberg, J.E.; Steinberg, J.; Liang, S.Y.; Trowbridge, J.; Campbell, M.; Balar, A.V. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021, 22, 872–882.
[8]	Rosenberg, J.; Sridhar, S.S.; Zhang, J.; Smith, D.; Ruether, D.; Flaig, T.W.; Baranda, J.; Lang, J.; Plimack, E.R.; Sangha, R.; Heath, E.I.; Merchan, J.; Quinn, D.I.; Srinivas, S.; Milowsky, M.; Wu, C.; Gartner, E.M.; Zuo, P.; Melhem-Bertrandt, A.; Petrylak, D.P. EV-101: a phase I study of single-agent enfortumab vedotin in patients with nectin-4-positive solid tumors, including metastatic urothelial carcinoma. J. Clin. Oncol. 2020, 38, 1041–1049.
[9]	Hoimes, C.J.; Rosenberg, J.E.; Srinivas, S.; Petrylak, D.P.; Milowsky, M.; Merchan, J.R.; Bilen, M.A.; Gupta, S.; Carret, A.S.; Yuan, N.; Melhem-Bertrandt, A.; Flaig, T. EV-103: initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Ann. Oncol. 2019, 30, v356.
[10]	Pace, A.; Brower, B.; Conway, D.; Leis, D. Enfortumab vedotin: nursing perspectives on the management of adverse events in patients with locally advanced or metastatic urothelial carcinoma. Clin. J. Oncol. Nurs. 2021, 25, E1–E9.
[11]	Eudravigilance Expert Working Group (EV-EWG). European Medicine Agency Guidelines, London. 2006, 1–22.
[12]	Bate, A.; Evans, S.J. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol. Drug Saf. 2009, 18, 427–436.
[13]	Rui, S.; Taku, F.; Lyu, C.B.; Setsuya, A. Severe eczematoid and lichenoid eruption with full-thickness epidermal necrosis developing from metastatic urothelial cancer treated with enfortumab vedotin. J. Dermatol. 2020, 47, 1436–1438.
[14]	Francis, A.; Jimenez, A.; Sundaresan, S.; Kelly, B. A rare presentation of enfortumab vedotin-induced toxic epidermal necrolysis. JAAD Case Rep. 2021, 7, 57–59.
[15]	Dobry, A.S.; Virgen, C.A.; Hosking, A.M.; Mar, N.; Doan, L.; Lee, B.; Smith, J. Cutaneous reactions with enfortumab vedotin: a case series and review of the literature. JAAD Case Rep. 2021, 14, 7–9.
[16]	Moussa, M.; Papatsoris, A.; Abou Chakra, M.; Dellis, A. Profile of enfortumab vedotin in the treatment of urothelial carcinoma: the evidence to date. Drug Des. Dev. Ther. 2021, 15, 453–462.
[17]	Jain, R.K.; Skelton, W.P. 4th, Zhang, J.S. Emerging treatment options for the treatment of metastatic urothelial cancer: therapeutic potential of enfortumab vedotin. Cancer Manag. Res. 2020, 12, 8379–8386.
[18]	Schaumberg, D.A.; Dana, R.; Buring, J.E.; Sullivan, D.A. Prevalence of dry eye disease among US men: estimates from the Physicians’ Health Studies. Clin. Interv. Aging 2009, 127, 763–768.
[19]	Maas, M.; Stühler, V.; Walz, S.; Stenzl, A.; Bedke, J. Enfortumab vedotin - next game-changer in urothelial cancer. Expert Opin. Biol. Ther. 2021, 21, 801–809.
[20]	Rosenberg, J.E.; O’Donnell, P.H.; Balar, A.V.; McGregor, B.A.; Heath, E.I.; Yu, E.Y.; Galsky, M.D.; Hahn, N.M.; Gartner, E.M.; Pinelli, J.M.; Liang, S.Y.; Melhem-Bertrandt, A.; Petrylak, D.P. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J. Clin. Oncol. 2019, 37, 2592–2600.

基于FAERS数据库的enfortumab vedotin的药物警戒评价

Pharmacovigilance evaluation of enfortumab vedotin using the FDA Adverse Event Reporting System

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 20

相关文章 0

编辑推荐

Metrics

本文评价