Session Title: Quick Fire Free Paper Session
Session Date/Time: Saturday 17/02/2018 | 11:45-13:00
Paper Time: 12:55
Venue: Ballroom II & III.
First Author: : M.Veselkova RUSSIAN FEDERATION
Co Author(s): : V. Zakharov N. Kislitsina S. Novikov S. Kolesnik A. Kolesnik
Polypoidal choroidal vasculopathy (PCV) is often considered to be a subtype of neovascular age-related macular degeneration. Currently, there are no long-term data available from large randomized controlled trials to evaluate the efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy (vPDT) in patients with PCV. The EVEREST II (NCT01846273) study was conducted to compare the efficacy and safety of ranibizumab combined with vPDT and ranibizumab monotherapy in patients with symptomatic macular PCV over 24 months.
EVEREST II was a 24-month, phase IV, randomized, double-masked, multicenter study, conducted in Asian patients with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography. A total of 322 patients were enrolled from seven Asian countries.
Treatment-naïve PCV patients (N=322) were randomized 1:1 to receive ranibizumab and vPDT (combination therapy arm; n=168) or ranibizumab and sham PDT (monotherapy arm; n=154). All enrolled patients received ranibizumab injections for three consecutive months (Day 1, Months 1 and 2) followed by a pro re nata (PRN) regimen according to the protocol-specific retreatment criteria, with at least 28 days between two ranibizumab injections. Patients also received vPDT/sham PDT on Day 1 followed by a PRN regimen based on the presence of active polypoidal lesions. Best-corrected visual acuity (BCVA) change at Months 12 (primary endpoint) and 24, complete polyp regression at Months 12 (primary endpoint) and 24, central sub field thickness (CSFT) change at Month 24, treatment exposure, and safety outcomes over 24 months were assessed. Following the results of the interim analysis at Month 12, 41 patients from the monotherapy arm at baseline were switched to combination therapy as pre-defined in the protocol. However, 113 patients from the monotherapy arm had already completed the study before the switch decision.
Overall, 85.1% (n = 274) of patients completed the 24-month study. At Month 12, combination therapy was superior to ranibizumab monotherapy in improving BCVA compared with baseline (+9.5 vs +5.7 letters; p=0.001) and achieving complete polyp regression (69.7% vs 33.8%; p<0.0001). The superiority of combination therapy over monotherapy, observed at Month 12, was maintained through Month 24, with respect to BCVA gains (+9.6 vs +5.5 letters; p=0.005) and complete polyp regression (56.6% vs 26.7%; p<0.0001). The mean reduction in CSFT from baseline at Month 3 was sustained over 24 months in both the arms, with a greater reduction in the combination therapy arm than the monotherapy arm (Month 24: 161.5 µm vs 125.0 µm; p<0.001). The mean number of ranibizumab injections prior to Months 12 and 24 in the combination arm was 5.1 and 8.1, respectively, in contrast to 7.4 and 12.3 injections, respectively, in the monotherapy arm. The mean number of vPDT treatments in the combination arm prior to Month 24 was 2.2, with 43.6% of patients requiring only the initial vPDT procedure. The safety profile was similar between both arms with no new safety signals.
The combination of ranibizumab and vPDT was superior to ranibizumab monotherapy in patients with symptomatic macular PCV, with respect to BCVA gains and complete polyp regression at Month 24, which is consistent with the Month 12 results. Treatment burden was reduced as these functional and anatomical outcomes were achieved with fewer ranibizumab injections in the combination therapy arm versus the monotherapy arm over 24 months. The safety profile was comparable between the combination therapy and monotherapy arms.