中华眼底病杂志

中华眼底病杂志

更换抗血管内皮生长因子药物治疗渗出型老年性黄斑变性的研究现状

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贝伐单抗、雷珠单抗等单抗类抗血管内皮生长因子(VEGF)药物及阿柏西普、康柏西普等融合蛋白类抗VEGF药物治疗渗出型老年性黄斑变性(AMD)的有效性已被临床证实,但仍有部分患者在治疗过程中存在不应答或应答不良的情况,此时更换药物成为应对的策略之一。通常情况下,当患者出现复发性AMD、对药物抵抗以及快速抗药反应时可考虑更换药物。目前的换药方案包括单抗类更换为融合蛋白类、融合蛋白类更换为单抗类、单抗类之间的替换以及单抗类更换为融合蛋白类再换回单抗类。但现今针对更换抗VEGF药物治疗渗出型AMD的研究多为回顾性、单臂研究,且不同研究所得结果存在些许差异;因此,对于抗VEGF药物治疗不应答或应答不良的渗出型AMD患者,采用换药治疗是否可以明确改善临床疗效,结论不一。但综合来看,换药有可能会改善患眼视网膜结构,但未必能获得视力的提高,其可以作为临床治疗方案中的一种选择。而对于何种换药方案可以获益最大,还需更大样本、更长研究时间的随机对照临床试验进一步探索。

Anti-vascular endothelial growth factor (VEGF) drugs, including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been clinically proven to be effective to treat exudative age-related macular degeneration AMD). However, there are still some patients do not or poorly respond to the initial anti-VEGF agents, usually after several injections, ophthalmologists may switch to another anti-VEGF agent. In general, switching of anti-VEGF agent is considered for recurrent AMD, AMD resistance to anti-VEGF treatments. Current switching protocols include the replacement of monoclonal antibodies with fusion protein agents, the replacement of fusion protein agents with monoclonal antibodies, the substitution of one monoclonal antibody with another one, and the replacement of monoclonal antibodies with fusion protein agents and switching back with monoclonal antibodies. However, current researches on the switching of anti-VEGF drugs for exudative AMD are mostly retrospective and single-arm studies, and there are some differences in the results of different studies. Therefore, for patients with exudative AMD who do not respond to or respond poorly to anti-VEGF drugs, the efficacy of switching of anti-VEGF drugs is uncertain right now. Switching of anti-VEGF agents may improve the retinal anatomical outcome of the affected eye but may not necessarily improve visual acuity. Thus it is an option in the clinical practice to treat AMD. To determine the benefits of above mentioned switching regimens, randomized controlled clinical trials with large sample number and long study period will be needed.

关键词: 湿性黄斑变性/药物疗法; 血管生成抑制剂/治疗应用; 抗体,单克隆/治疗应用; 综述

Key words: Wet macular degeneration/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Review

引用本文: 刘畅, 孙大卫. 更换抗血管内皮生长因子药物治疗渗出型老年性黄斑变性的研究现状. 中华眼底病杂志, 2017, 33(6): 662-664. doi: 10.3760/cma.j.issn.1005-1015.2017.06.032 复制

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1. Ehlers JP, Spirn MJ, Shah CP, et al. Ranibizumab for exudative age-related macular degeneration in eyes previously treated with alternative vascular endothelial growth factor inhibitors [J]. Ophthalmic Surg Lasers Imaging, 2010, 41(2): 182-189. DOI: 10.3928/15428877-20100303-05.
2. Ferrone PJ, Anwar F, Naysan J, et al. Early initial clinical experience with intravitreal aflibercept for wet age-related macular degeneration [J]. Br J Ophthalmol, 2014, 98(Suppl 1): S17-21. DOI: 10.1136/bjophthalmol-2013-304474.
3. Miura M, Iwasaki T, Goto H. Intravitreal aflibercept for polypoidal choroidal vasculopathy after developing ranibizumab tachyphylaxis[J]. Clin Ophthalmol, 2013, 7: 1591-1595. DOI: 10.2147/OPTH.S50634.
4. Gharbiya M, Iannetti L, Parisi F, et al. Visual and anatomical outcomes of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration [J/OL]. Biomed Res Int, 2014, 2014: 1-7[2014-05-07]. https://dx.doi.org/10.1155/2014/273754. DOI: 10.1155/2014/273754.
5. Michalewski J, Nawrocki J, Trębińska M, et al. Switch to a single dose of aflibercept in bevacizumab nonresponders with AMD[J]. Can J Ophthalmol, 2014, 49(5): 431-435. DOI: 10.1016/j.jcjo.2014.07.012.
6. Yang J, Wang X, Fuh G, et al. Comparison of binding characteristics and in vitro activities of three inhibitors of vascular endothelial growth factor A[J]. Mol Pharm, 2014, 11(10): 3421-3430. DOI: 10.1021/mp500160v.
7. Vorum H, Olesen TK, Zinck J, et al. Real world evidence of use of anti-VEGF therapy in Denmark[J]. Curr Med Res Opin, 2016, 32(12): 1943-1950. DOI: 10.1080/03007995.2016.1221803.
8. Su L, Ren X, Wei H, et al. Intravitreal conbercept therapy (KH902) for surgical treatment of severe proliferative diabetic retinopathy[J]. Retina, 2016, 36(5): 938-943. DOI: 10.1097/IAE.0000000000000900.
9. Mantel I, Gianniou C, Dirani A. Conversion to aflibercept therapy versus continuing with ranibizumab therapy for neovascular age-related macular degeneration dependent on monthly ranibizumab treatment[J]. Retina, 2016, 36(1): 53-58. DOI: 10.1097/IAE.0000000000000664.
10. Aslankurt M, Aslan L, Aksoy A, et al. The results of switching between 2 anti-VEGF drugs, bevacizumab and ranibizumab, in the treatment of neovascular age-related macular degeneration [J]. Eur J Ophthalmol, 2013, 23(4): 553-557. DOI: 10.5301/ejo.5000268.
11. Ehlken C, Jungmann S, Böhringer D, et al. Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD [J]. Eye (Lond), 2014, 28(5): 538-545. DOI: 10.1038/eye.2014.64.
12. Gerding H. Functional and anatomic efficacy of a conversion to aflibercept in eyes with age-related macular degeneration after long-term ranibizumab treatment [J]. Klin Monbl Augenheilkd, 2015, 232(4): 560-563. DOI: 10.1055/s-0035-1545775.
13. Fassnacht-Riederle H, Becker M, Graf N, et al. Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(11): 1705-1709. DOI: 10.1007/s00417-014-2589-3.
14. Messenger WB, Campbell JP, Faridi A, et al. Injection frequency and anatomic outcomes 1 year following conversion to aflibercept in patients with neovascular age-related macular degeneration[J]. Br J Ophthalmol, 2014, 98(9): 1205-1207. DOI: 10.1136/bjophthalmol-2013-304829.
15. Seguin-Greenstein S, Lightman S, Tomkins-Netzer O. A meta-analysis of studies evaluating visual and anatomical outcomes in patients with treatment resistant neovascular age-related macular degeneration following switching to treatment with aflibercept[J/OL]. J Ophthalmol, 2016, 2016: 4095852[2016-03-06]. https://dx.doi.org/10.1155/2016/4095852. DOI: 10.1155/2016/4095852.
16. Waizel M, Rickmann A, Blanke BR, et al. Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD[J]. Eur J Ophthalmol, 2016, 26(5): 469-472. DOI: 10.5301/ejo.5000781.
17. Pinheiro-Costa J, Freitas-da-Costa P, Falcão MS, et al. Switch from intravitreal ranibizumab to bevacizumab for the treatment of neovascular age-related macular degeneration: clinical comparison[J]. Ophthalmologica, 2014, 232(3): 149-155.DOI: 10.1159/000363422.
18. Karagiannis DA, Ladas ID, Parikakis E, et al. Changing from bevacizumab to ranibizumab in age-related macular degeneration: is it safe? [J]. Clin Interv Aging, 2009, 4: 457-461.
19. Despreaux R, Cohen SY, Zambrowski O, et al. Short-term results of switchback from aflibercept to ranibizumab in neovascular age-related macular degeneration in clinical practice[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(4): 639-644. DOI: 10.1007/s00417-015-3084-1.
20. Nudleman E, Wolfe JD, Woodward MA, et al. Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab[J]. Clin Ophthalmol, 2016, 10: 1053-1057. DOI: 10.2147/OPTH.S109894.