Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol.

ABSTRACT

PURPOSE: To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat-and-extend protocol for the treatment of neovascular age-related macular degeneration (AMD). DESIGN: Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters. PARTICIPANTS: Patients aged ≥ 50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity (BCVA) between 20/25 and 20/320. METHODS: Patients were randomly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections. Monthly injections were given until inactive disease was achieved. The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks. If signs of recurrent disease appeared, the treatment interval was shortened by 2 weeks at a time. MAIN OUTCOME MEASURES: Change in visual acuity at 1 year. RESULTS: Between March 2009 and July 2012, 441 patients were randomized at 10 ophthalmological centers in Norway. The 1-year visit was completed by 371 patients. In the per protocol analysis at 1 year, bevacizumab was equivalent to ranibizumab, with 7.9 and 8.2 mean letters gained, respectively (95% confidence interval [CI] of mean difference, -2.4 to 2.9; P = 0.845). The intention-to-treat analysis was concordant. There was no significant difference in measured central retinal thickness (CRT), with a mean decrease of -112 µm for bevacizumab and -120 µm for ranibizumab (95% CI of mean difference, -13 to 28; P = 0.460). There was a statistically significant difference (P = 0.001) between the drugs regarding the number of treatments 8.9 for bevacizumab and 8.0 for ranibizumab. There were fewer arteriothrombotic events in the bevacizumab group (1.4%) than in the ranibizumab group (4.5%) (P = 0.050) and significantly more cardiac events in the ranibizumab group (P = 0.036). However, patients treated with ranibizumab more often had a history of myocardial infarction (P = 0.021). CONCLUSIONS: Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat-and-extend protocol. The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment. The numbers of serious adverse events were small.