贝伐珠单抗眼部用药相关不良事件回顾性研究

摘要/Abstract

摘要： 目的：挖掘并分析贝伐珠单抗超说明书用于新生血管性眼科疾病的药品不良事件（ADE）信号，指导临床合理用药。方法：基于FAERS数据库，收集2013～2023年间贝伐珠单抗眼部用药的ADE报告，应用比例失衡法挖掘ADE信号。结果：共收集ADE报告1 612例，主要涉及新生血管性年龄相关性黄斑变性等，发现不良反应首选语（PT）3 014个，显著风险集中于眼器官疾病与感染，且受玻璃体注射方式、制剂特性、给药形式及剂量影响。结论：贝伐珠单抗超说明书用于眼部疾病时，需密切关注其ADE。

关键词: font-size:medium, ">贝伐珠单抗；眼部疾病；不良事件；超说明书用药

Abstract: Objective： To identify and analyze adverse drug event（ADE) signals associated with the off-label use of bevacizumab in neovascular ophthalmic diseases， providing a basis for rational clinical drug use. Methods： ADE reports of bevacizumab for ocular conditions from 2013 to 2023 were collected from the FAERS database. The proportional imbalance method was applied to mine ADE signals. Results： A total of 1612 ADE reports were collected， primarily related to neovascular age-related macular degeneration（nAMD) among others. A total of 3，014 preferred terms（PT) of adverse reactions were identified， with significant risks concentrated in ocular organ diseases and infections. These ADEs were influenced by factors such as intravitreal injection technique， formulation characteristics， route of administration， and dosage. Conclusion： When bevacizumab is used off-label for ocular diseases， close attention must be paid to its adverse events.

Key words: font-size:medium, ">Bevacizumab； Eye diseases； Adverse event； Off-label use

中图分类号:

孙冠男1, 陈礼怡2, 何明珠2, 张焜2, 颜久兴2. 贝伐珠单抗眼部用药相关不良事件回顾性研究[J]. 中国药物评价, 2024, 41(5): 424-428.

SUN Guan-nan1, CHEN Li-yi2, HE Ming-zhu2, ZHANG Kun2, YAN Jiu-xing2. Retrospective Study on Adverse Events Related to Bevacizumab Eye Medication[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2024, 41(5): 424-428.

参考文献

[1] 周振兴，宋军民，陈姬华，等.贝伐珠单抗在肿瘤治疗中的应用研究进展[J].药学进展，2015，39(7): 525-532.
     [2] Ferrara N. Vascular endothelial growth factor: basic science and clinical progress[J]. Endocrine reviews， 2004， 25(4): 581-611.
     [3] Martin DF， Maguire MG， Ying GS， et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration[J]. The New England journal of medicine， 2011， 364(20): 1897-1908.
     [4] Maloney MH， Payne SR， Herrin J， et al. Risk of Systemic Adverse Events after Intravitreal Bevacizumab， Ranibizumab， and Aflibercept in Routine Clinical Practice[J]. Ophthalmology，2021，128(3):417-424.
     [5] Cox JT， Eliott D， Sobrin L. Inflammatory Complications of Intravitreal Anti-VEGF Injections[J]. J Clin Med，2021，10(5):981.
     [6] 薛逸非，李光耀，张弨.国内外超说明书使用贝伐珠单抗治疗新生血管性年龄相关性黄斑变性现状及相关原因分析[J].中国新药杂志，2022，31(8):813-818.
     [7] Greenberg JP， Belin P， Butler J， et al. Aflibercept-related sterile intraocular inflammation outcomes[J]. Ophthalmol Retina，2019，9:753-759.
     [8] Williams PD， Chong D， Fuller T， et al. Noninfectious vitritis after intravitreal injection of anti-vegf agents: variations in rates and presentation by medication[J]. Retina，2016，6(5):909-913.
     [9] Georgopoulos M， Polak K， Prager F，et al. Characteristics of severe intraocular inflammation following intravitreal injection of bevacizumab（Avastin) [J]. Br J Ophthalmol， 2009，93(4):457-462.
     [10] GroupVISiONCT， D′Amico DJ， Masonson HN， et al. Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective， multicenter， controlled clinical trials[J]. Ophthalmology，2006，113(6):992-1001.
     [11] Wickremasinghe SS， Michalova K， Gilhotra J， et al. Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration[J]. Ophthalmology，2008，115(11):1911-1915.
     [12] Group CR， Martin DF， Maguire MG， et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration[J]. N Engl J Med，2011，364(20):1897-1908.
     [13] Baeshen MN， Al-Hejin AM， Bora RS， et al. Production of biopharmaceuticals in E. coli: current scenario and future perspectives[J]. J MicrobiolBiotechnol，2015，25(7):953-962.
     [14] Pranchevicius MC， Vieira TR. Production of recombinant immunotherapeutics for anticancer treatment: the role of bioengineering[J]. Bioengineered，2013，4(5):305-312.
     [15] Wang F， Yu S， Liu K， Chen FE， et al. Acute intraocular inflammation caused by endotoxin after intravitreal injection of counterfeit bevacizumab in Shanghai China[J]. Ophthalmology，2013，120(2):355-361.
     [16] Krayukhina E， Tsumoto K， Uchiyama S， et al. Effects of syringe material and silicone oil lubrication on the stability of pharmaceutical proteins[J]. J Pharm Sci，2015，104(2):527-535.
     [17] Liu L， Ammar DA， Ross LA， et al. Silicone oil microdroplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling[J]. Invest Ophthalmol Vis Sci， 2011，52(2):1023-1034.
     [18] Torisu T， Maruno T， Yoneda S， et al. Friability testing as a new stress-stability assay for biopharmaceuticals[J]. J Pharm Sci，2017，106(10):2966-2978.
     [19] Avery RL， Castellarin AA， Steinle NC， et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab， bevacizumab or aflibercept in patients with neovascular AMD[J]. Br J Ophthalmol， 2014， 98(12):1636-1641.
     [20] Starr MR， Dalvin LA， AbouChehade JE， et al. Classification of strokes in patients receiving intravitreal anti-vascular endothelial growth factor[J]. Ophthalmic Surg Lasers Imaging Retina，2019，50(5):140-157.
     [21] Xu Y， Tan CS. Safety and complications of intravitreal injections performed in an Asian population in Singapore[J]. Int Ophthalmol，2017，37(2):325-332.
     [22] Zehden JA， Mortensen XM， Reddy A， et al. Systemic and Ocular Adverse Events with Intravitreal Anti-VEGF Therapy Used in the Treatment of Diabetic Retinopathy: a Review[J]. Curr Diab Rep， 2022，22(5)， 525-536.