Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study_Chinese Journal of Ocular Fundus Diseases

Authors：

 Li Xiaoxin ¹ , Chen Youxin ² , Zhang Junjun ³ , Xu Xun ⁴ , Zhang Feng ⁵ , Chui Ming Gemmy Cheung ⁶ , Rui Yu ⁷ , Husain Kazmi ⁸ , Olaf Sowade ⁹ , Oliver Zeitz on behalf of the SIGHT study group ⁹

1. Department of Ophthalmology, Peking University People's Hospital; Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100044, China;
2. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China;
3. Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu 610041, China;
4. Department of Ophthalmology, Shanghai General Hospital, Shanghai 200080;
5. Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
6. Department of Ophthalmology, Singapore Eye Research Institute, Singapore;
7. Department of Ophthalmology, Bayer US, Whippany, New York;
8. Ophthalmology, Regeneron Pharmaceuticals, Inc., Tarrytown, New York;
9. Development, Pharmaceuticals, Bayer AG, Berlin, Germany;

Corresponding author：

Li Xiaoxin, Email: dr_lixiaoxin@163.com

Keywords：

Wet macular degeneration/drug therapy; Choroidal neovascularization/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Photochemotherapy

DOI：

10.3760/cma.j.issn.1005-1015.2019.02.010

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ObjectiveTo assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).ResultsAmong the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to-IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged ＜65, and those with active CNV lesion area ＜50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions.ConclusionsThe efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before.

Citation： Li Xiaoxin, Chen Youxin, Zhang Junjun, Xu Xun, Zhang Feng, Chui Ming Gemmy Cheung, Rui Yu, Husain Kazmi, Olaf Sowade, Oliver Zeitz on behalf of the SIGHT study group. Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study. Chinese Journal of Ocular Fundus Diseases, 2019, 35(2): 156-165. doi: 10.3760/cma.j.issn.1005-1015.2019.02.010 Copy

1.	Wong WL, Su X, Li X, et al. Global prevalence of agerelated macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis[J]. Lancet Glob Health, 2014, 2(2): 106-116. DOI: 10.1016/S2214-109X(13)70145-1.
2.	Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1432-1444. DOI: 10.1056/NEJMoa062655.
3.	Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study[J]. Ophthalmology, 2009, 116(1): 57-65. DOI: 10.1016/j.ophtha.2008.10.018.
4.	Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials-TAP report[J]. Arch Ophthalmol, 1999, 117(10): 1329-1345. DOI: 10.1001/archopht.117.10.1329.
5.	陈有信, 葛坚, 严密, 等. 中国维替泊芬光动力疗法治疗年龄相关性黄斑变性中心凹下脉络膜新生血管的多中心临床研究[J]. 中华眼科杂志, 2007, 43(3): 198-205. DOI: 10.3760/j.issn.0412-4081.2007.03.003.Chen YX, Ge J, Yan M, et al. Clinical trial of verteporfin photodynamic therapy in Chinese age-related macular degeneration with subfoveal predominant choroidal neovascularization patients[J]. Chin J Ophthalmol, 2007, 43(3): 198-205. DOI: 10.3760/j.issn.0412-4081.2007.03.003.
6.	Yoon JU, Byun YJ, Koh HJ. Intravitreal anti-VEGF versus photodynamic therapy with verteporfin for treatment of myopic choroidal neovascularization[J]. Retina, 2010, 30(3): 418-424. DOI: 10.1097/IAE.0b013e3181bd2fe4.
7.	Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration[J]. Ophthalmology, 2012, 119(12): 2537-2548. DOI: 10.1016/j.ophtha.2012.09.006.
8.	Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEWstudies[J]. Ophthalmology, 2014, 121(1): 193-201. DOI: 10.1016/j.ophtha.2013.08.011.
9.	Wong TY, Ogura Y. 2-year (96-week) efficacy and safety of intravitreal aflibercept injection for neovascular age-related macular degeneration in Asian patients: subgroup analysis of VIEW studies[C]. World Ophthalmology Congress, Tokyo, Japan, 2014.
10.	Sivaprasad S, Saleh GM, Jackson H. Does lesion size determine the success rate of photodynamic therapy for agerelated macular degeneration?[J]. Eye (Lond.), 2006, 20(1): 43-45. DOI: 10.1038/sj.eye.6701787.
11.	Verteporfin Roundtable Participants. Guidelines for using verteporfin (Visudyne) in photodynamic therapy for choroidal neovascularization due to age-related macular degeneration and other causes: update[J]. Retina, 2005, 25(2): 119-134. DOI: 10.1097/00006982-200502000-00002.
12.	Suner IJ, Kokame GT, Yu E, et al. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials[J]. Invest Ophthalmol Vis Sci, 2009, 50(8): 3629-3635. DOI: 10.1167/iovs.08-3225.
13.	Brown DM, Shapiro H, Schneider S. Subgroup analysis of first-year results of ANCHOR: a phase Ⅲ, double-masked, randomized comparison of ranibizumab and verteporfin photodynamic therapy for predominantly classic choroidal neovascularization related to age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2006, 47: 2963.
14.	Kaiser PK, Brown DM, Zhang K, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results[J]. Am J Ophthalmol, 2007, 144(6): 850-857. DOI: 10.1016/j.ajo.2007.08.012.
15.	ICH Harmonised Tripartite Guideline. Ethnic factors in the acceptability of foreign clinical data EH(R1)[EB/OL](2016-04-18). http://www.ich.org/products/guidelines/efficacy/article/efficacyguidelines.html.

1. Wong WL, Su X, Li X, et al. Global prevalence of agerelated macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis[J]. Lancet Glob Health, 2014, 2(2): 106-116. DOI: 10.1016/S2214-109X(13)70145-1.
2. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1432-1444. DOI: 10.1056/NEJMoa062655.
3. Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study[J]. Ophthalmology, 2009, 116(1): 57-65. DOI: 10.1016/j.ophtha.2008.10.018.
4. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials-TAP report[J]. Arch Ophthalmol, 1999, 117(10): 1329-1345. DOI: 10.1001/archopht.117.10.1329.
5. 陈有信, 葛坚, 严密, 等. 中国维替泊芬光动力疗法治疗年龄相关性黄斑变性中心凹下脉络膜新生血管的多中心临床研究[J]. 中华眼科杂志, 2007, 43(3): 198-205. DOI: 10.3760/j.issn.0412-4081.2007.03.003.Chen YX, Ge J, Yan M, et al. Clinical trial of verteporfin photodynamic therapy in Chinese age-related macular degeneration with subfoveal predominant choroidal neovascularization patients[J]. Chin J Ophthalmol, 2007, 43(3): 198-205. DOI: 10.3760/j.issn.0412-4081.2007.03.003.
6. Yoon JU, Byun YJ, Koh HJ. Intravitreal anti-VEGF versus photodynamic therapy with verteporfin for treatment of myopic choroidal neovascularization[J]. Retina, 2010, 30(3): 418-424. DOI: 10.1097/IAE.0b013e3181bd2fe4.
7. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration[J]. Ophthalmology, 2012, 119(12): 2537-2548. DOI: 10.1016/j.ophtha.2012.09.006.
8. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEWstudies[J]. Ophthalmology, 2014, 121(1): 193-201. DOI: 10.1016/j.ophtha.2013.08.011.
9. Wong TY, Ogura Y. 2-year (96-week) efficacy and safety of intravitreal aflibercept injection for neovascular age-related macular degeneration in Asian patients: subgroup analysis of VIEW studies[C]. World Ophthalmology Congress, Tokyo, Japan, 2014.
10. Sivaprasad S, Saleh GM, Jackson H. Does lesion size determine the success rate of photodynamic therapy for agerelated macular degeneration?[J]. Eye (Lond.), 2006, 20(1): 43-45. DOI: 10.1038/sj.eye.6701787.
11. Verteporfin Roundtable Participants. Guidelines for using verteporfin (Visudyne) in photodynamic therapy for choroidal neovascularization due to age-related macular degeneration and other causes: update[J]. Retina, 2005, 25(2): 119-134. DOI: 10.1097/00006982-200502000-00002.
12. Suner IJ, Kokame GT, Yu E, et al. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials[J]. Invest Ophthalmol Vis Sci, 2009, 50(8): 3629-3635. DOI: 10.1167/iovs.08-3225.
13. Brown DM, Shapiro H, Schneider S. Subgroup analysis of first-year results of ANCHOR: a phase Ⅲ, double-masked, randomized comparison of ranibizumab and verteporfin photodynamic therapy for predominantly classic choroidal neovascularization related to age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2006, 47: 2963.
14. Kaiser PK, Brown DM, Zhang K, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results[J]. Am J Ophthalmol, 2007, 144(6): 850-857. DOI: 10.1016/j.ajo.2007.08.012.
15. ICH Harmonised Tripartite Guideline. Ethnic factors in the acceptability of foreign clinical data EH(R1)[EB/OL](2016-04-18). http://www.ich.org/products/guidelines/efficacy/article/efficacyguidelines.html.

Chinese Journal of Ocular Fundus Diseases

Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study

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