Session Title: AMD II
Session Date/Time: Friday 27/09/2013 | 08:00-10:00
Paper Time: 08:00
Venue: Hall 3 (Level 0)
First Author: P.Schlottmann ARGENTINA
Co Author(s): Z. Li L. Tuomi J. Nau
HARBOR evaluated the efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered on a monthly or as-needed (PRN) basis after 3 monthly loading doses in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD).
A 24-month, phase III, randomized, multicenter, double-masked, dose-response study with 100 investigator sites and 1098 randomized patients.
Patients aged ≥50 years were randomized in a 1:1:1:1 ratio to 1 of 4 ranibizumab treatment groups: 0.5 mg monthly (n=275); 0.5 mg PRN (n=275); 2.0 mg monthly (n=274) and 2.0 mg PRN (n=273). The primary efficacy endpoint was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary endpoints included the mean change from baseline in BCVA at month 24, the proportion of patients who gained ≥15 letters in BCVA, the mean number of ranibizumab injections, and the mean change from baseline in central foveal thickness (CFT) over time. Ocular and systemic safety events were also evaluated through month 24.
At month 24, the mean change from baseline in BCVA was (letters): +9.1 (0.5 mg monthly), +7.9 (0.5 mg PRN), +8.0 (2.0 mg monthly), and +7.6 (2.0 mg PRN), respectively. The change in mean BCVA from month 12 to 24 was (letters): −1.0, −0.3, −1.2, and −1.0, respectively. The proportion of patients who gained ≥15 letters from baseline in BCVA through month 24 was: 34.5% (0.5mg monthly), 33.1% (0.5 mg PRN), 37.6% (2.0 mg monthly), and 34.8% (2.0 mg PRN). The mean number of injections during year 2 was 5.6 (0.5 mg PRN) and 4.3 (2.0 mg PRN). For those that completed the 24-month study period in the 0.5 mg PRN group, the total injections needed per patient ranged from 3 to 24 over 2 years; the average injection frequency was 9.9 weeks after 3 monthly loading doses and 93% of patients did not require monthly dosing. Mean change from baseline in CFT at month 24 was (μm): -182.5 (0.5 mg monthly), -172.0 (0.5 mg PRN), -171.8 (2.0 mg monthly), and -181.0 (2.0 mg PRN). The ocular and systemic safety profile in year 2 was similar between all 4 treatment groups, and was consistent with previous ranibizumab trials in AMD.
At month 24, mean BCVA improvements were clinically significant and meaningful for all 4 treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 5.6 injections needed in year 2. The majority (93%) of these patients did not require monthly dosing over 2 years, indicating that an individualized treatment approach may be appropriate for most patients. The average treatment duration during the PRN period was 9.9 weeks.