Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration.

OBJECTIVE: To evaluate the 24-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly or as needed (pro re nata [PRN]) in patients with neovascular age-related macular degeneration (wet AMD).

DESIGN: Twenty-four-month, multicenter, randomized, double-masked, active treatment-controlled phase 3 trial.

PARTICIPANTS: Patients (n = 1098) ≥ 50 years of age with treatment-naïve subfoveal wet AMD.

METHODS: Patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or 2.0 mg monthly or PRN after 3 monthly loading doses.

MAIN OUTCOME MEASURES: The primary efficacy end point was the mean change in best-corrected visual acuity (BCVA) from baseline at month 12. Key secondary end points included mean change in BCVA from baseline at month 24, proportion of patients who gained ≥ 15 letters in BCVA, mean number of ranibizumab injections, and mean change in central foveal thickness from baseline over time by spectral-domain optical coherence tomography. Ocular and systemic safety events also were evaluated through month 24.

RESULTS: 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). 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 at month 24 was 34.5%, 33.1%, 37.6%, and 34.8%, respectively. The mean number of ranibizumab injections through month 24 was 21.4, 13.3, 21.6, and 11.2, respectively; 5.6 and 4.3 mean injections were required in year 2 in the 0.5 mg and 2.0 mg PRN groups, respectively. The average treatment interval in the 0.5 mg PRN group was 9.9 weeks after 3 monthly loading doses, and 93% of these patients did not require monthly dosing. Ocular and systemic safety profiles over 2 years were similar among all 4 treatment groups and were consistent with previous ranibizumab trials in AMD.

CONCLUSIONS: At month 24, mean BCVA improvements were clinically meaningful and similar among all 4 ranibizumab treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 13.3 injections (5.6 injections in year 2). No new safety events were identified over 24 months.