阿柏西普玻璃体腔注射和光动力疗法治疗中国新生血管性老年性黄斑变性患者的疗效对比:SIGHT研究

摘要

目的 对比观察玻璃体注射阿柏西普(IAI)和光动力疗法(PDT)治疗中国继发于新生血管性老年性黄斑变性(nAMD)的经典为主型脉络膜新生血管(CNV)患者的安全性和有效性.方法 随机、双盲、多中心为期52周(2011年12月至2014年8月)的Ⅲ期临床研究.研究注册码NCT01482910.入组患者按照3:1比例随机分为IAI组、PDT→IAI组.IAI组患者在基线和第4、8、16、24、32、40、48周时接受2mg IAI治疗,第28、36周时分别接受假注射治疗.PDT→IAI组患者在基线时均强制接受1次PDT治疗,第12、24周时若满足PDT再治疗条件,则再次予以PDT治疗;基线和第4、8、16、24周时接受假注射治疗,第28、32、36、40、48周时接受2 mg IAI治疗.报告的主要有效性结果为第28周时平均BCVA相较基线的变化和第52周时的结果.安全性评价包括发生治疗相关不良事件(TEAEs)患者百分比.结果 人组304例患者中,IAI组、PDT→IAI组分别为228、76例.第28周时,IAI组、PDT→IAI组患者平均BCVA较基线变化值分别为+14.0、+3.9个字母;第52周时,两组患者BCVA较基线变化值分别为+15.2、+8.9个字母,差异为+6.2个字母(95％ CI 2.6～9.9,P=0.000 9).第52周时,两组患者平均中心凹视网膜厚度分别下降-189.6、-170.0 μm.IAI组中BCVA提高最为显著者为年龄＜65岁、活动性CNV面积＜总病灶面积50％者.IAI组、PDT→IAI组患者眼部最常见TEAEs为黄斑纤维化[1 1.8％(27/228)、6.6％(5/76)]、BCVA下降[6.6％(15/228)、21.1％(16/76)].抗血小板研究合作组定义的动脉血栓栓塞事件3例,但均被认为与药物无关.结论 中国nAMD患者阿柏西普治疗效果优于PDT.阿柏西普疗效在全部患者中均可持续至第52周.不良事件的发生率与已知的阿柏西普安全性数据一致.%Objective To assess the efficacy and safety ofintravitreal 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).Methods A randomized,double-blind,multi-center phase-3 clinical trial lasting for 52weeks (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).Results Among 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.Conclusions The 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.