Session Title: AMD II
Session Date/Time: Friday 18/09/2015 | 14:30-16:00
Paper Time: 14:46
First Author: : X.Li CHINA
Co Author(s): : Y. Chen J. Zhang X. Xu H. Wu O. Sowade O. Zeitz
PURPOSE:The prevalence of wet age-related macular degeneration (wAMD) is growing at a faster rate in Asia compared with other regions which may due to a larger ageing population. Photodynamic therapy (PDT) is effective in the treatment of wAMD, but anti-vascular endothelial growth factor (VEGF) agents have been shown to be superior. However, there are no randomised studies comparing PDT with intravitreal aflibercept (IVT-AFL) in Asian patients. The aim of the SIGHT study was to assess the efficacy and safety of IVT-AFL versus PDT in Chinese patients with wAMD.
The study was conducted from December 2011 to August 2014 in 14 sites across China.
SIGHT was a 52-week, multicentre, double-masked, Phase 3 study in which patients with predominantly classic choroidal neovascularisation (CNV) secondary to wAMD were randomised 3:1 to IVT-AFL (2.0 mg every 8 weeks after 3 initial monthly injections)/sham PDT or active PDT/sham IVT-AFL. Patients treated with active PDT/sham IVT-AFL received IVT-AFL at Week 28 (PDT→ IVT-AFL). Primary endpoint was mean change in best-corrected visual acuity (BCVA) (ETDRS letters) from baseline to Week 28 and secondary (confirmatory) endpoint was loss of fewer than 15 letters at Week 28. We report the Week 52 results. Efficacy endpoints were performed using the full analysis set (randomised patients who received any study drug and had baseline and at least 1 post-baseline BCVA assessment). BCVA and central retinal thickness (CRT) were analysed using an analysis of covariance method, and binary endpoints were analysed using a Cochrane-Mantel-Haenszel method. A last observation carried forward approach was applied for imputing missing values. Week 52 analyses were exploratory and P-values are descriptive. 304 patients were randomised to IVT-AFL (n=228) or PDT→ IVT-AFL (n=76). Mean age was 65.1 years, mean CNV lesion size was 1.828 mm(2) and 34.9% had a CNV lesion less than 50% of the total lesion size at baseline.
Mean change in BCVA (IVT-AFL versus PDT→ IVT-AFL) was +14.0 vs +3.9 letters (Week 28) and +15.2 letters versus +8.9 letters (Week 52); between-group difference [95% confidence interval (CI)] was 6.2 [2.6 to 9.9] (P less than 0.001) (Week 52). Proportion of patients that lost fewer than 15 letters (IVT-AFL versus PDT→ IVT-AFL) was 98.7% versus 92.1% (Week 28) and 97.4% versus 90.8% (Week 52); between-group difference [95% CI] was 6.7 [-0.1 to 13.5] (P=0.052) (Week 52). Mean CRT reduction was -189.6 µm (IVT-AFL) versus -170.0 µm (PDT→ IVT-AFL) (Week 52); between-group difference [95% CI] was -27.0 [-45.9 to -8.2] (P less than 0.01). For patients entering the second half of the year, there was a clinically meaningful improvement from Weeks 28 to 52 after switching from PDT to IVT-AFL where the further mean improvement in BCVA was +5.4 letters and further mean reduction in CRT was -76.9 µm. The most common ocular treatment-emergent adverse events (AEs) (study eye) were macular fibrosis (10.5% [n=32]) and reduced visual acuity (10.2% [n=31]). There was no endophthalmitis reported. Only 3 treatment-emergent Antiplatelet Trialists’ Collaboration–defined arterial thromboembolic events (nonfatal stroke  and nonfatal myocardial infarction ) were observed but were considered not drug-related.
Results from the primary and confirmatory secondary efficacy endpoints showed that IVT-AFL (2 mg every 8 weeks after 3 initial monthly injections) was clinically and statistically superior to PDT treatment at Week 28 in Chinese patients with wAMD. Strong superiority was even shown in a population where PDT obviously worked much better than in most previous studies with PDT. The visual and morphological improvements in the IVT-AFL group were maintained with a trend of further improvement through week 52. Substantial visual and morphological improvements were also observed in the PDT→IVT-AFL group after initiating IVT-AFL at Week 28. IVT-AFL was well tolerated with a favourable safety profile. These findings are novel and clinically relevant in that this is the first study to demonstrate the 52-week benefits of IVT-AFL versus PDT in an Asian population, which was, in this case, a population with a lower mean age and smaller active component of the CNV lesion compared to previous anti-VEGF studies in wAMD patients. The results post-Week 28 indicate also that early use of IVT-AFL may convey greater benefits than later initiation.