Efficacy of intravitreal ranibizumab given bimonthly versus PRN in patients with neovascular age-related macular degeneration: 1 year results of a prospective, randomized clinical trial.

Abstract

Purpose: To compare the efficacy of intravitreal ranibizumab using bimonthly or as-needed (PRN) dosing in patients with neovascular age-related macular degeneration (AMD).

Methods: Prospective, singlecenter, randomized, investigator-initiated clinical trial (IIT). Patients with treatment-naïve, subfoveal choroidal neovascularization secondary to AMD received 3 initial monthly injections of 0.5mg ranibizumab followed by (a) bimonthly or (b) PRN dosing of 0.5mg ranibzumab. Primary endpoint was non-inferiority of the bimonthly regime to PRN regarding change in best-corrected visual acuity from baseline to week 52 (losing <12 letters on Early Treatment Diabetic Retinopathy (ETDRS) charts). Secondary endpoints were number of injections and changes in retinal thickness. Retreatment criteria were loss of >5 letters or increase in retinal thickness >100µm as compared to the data from the reference visit 4 (RV4) 2 weeks after the upload phase.

Results: 40 (20/20) patients were included and analyzed. Ranibizumab given bimonthly was non-inferior (p<0.0001, t-test) but not superior (p=0.2868) to PRN for the primary endpoint. Baseline visual acuity was between 57 and 58 letters in both groups. Visual acuity improved significantly by 7.15 letters in the PRN group (95%-CI: [2.05; 12.25]) and 10.65 letters in the bimonthly-injected group ([6.18; 15.12]) (difference between both groups 3.5 letters). The mean difference in change from RV4 to week 52 between the groups was 1.05 letters (non-inferiority: p<0.0001, superiority: 0.6711, t-test). The proportion of patients gaining ≥15 letters was 40% (PRN) and 30% (bimonthly). Median retinal thickness decreased by 198µm (PRN) and 123.5 µm (bimonthly). The median numbers of injections were 4 (PRN) and 8 (bimonthly). 8 PRN patients (40%) were adequately treated with 3 injections up to week 52.

Conclusions: Intravitreal ranibizumab dosed every 2 months or PRN produced similar efficacy with half as many injections in the PRN arm. In both treatment groups visual gain after 3 initial monthly injections could be maintained up to week 52. Provided monthly visits take place, the risk-benefit assessment favors PRN dosing in terms of similar visual results and less number of injections.

Keywords: 412 age-related macular degeneration • 688 retina • 748 vascular endothelial growth factor