Allen C Ho1, Brandon G Busbee2, Carl D Regillo3, Mark R Wieland4, Sherri A Van Everen5, Zhengrong Li5, Roman G Rubio5, Phillip Lai5. 1. Mid Atlantic Retina, Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address: acho@att.net. 2. Tennessee Retina, Nashville, Tennessee. 3. Mid Atlantic Retina, Wills Eye Hospital, Philadelphia, Pennsylvania. 4. Northern California Retina Vitreous Associates, Mountain View, California. 5. Genentech, Inc., South San Francisco, California.
Abstract
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.
RCT Entities:
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.
Authors: Kunny C Dans; Sarah R Freeman; Tiezhu Lin; Amit Meshi; Sergio Olivas; Lingyun Cheng; Manuel J Amador-Patarroyo; William R Freeman Journal: Graefes Arch Clin Exp Ophthalmol Date: 2019-02-26 Impact factor: 3.117