Ranibizumab and bevacizumab for neovascular age-related macular degeneration

Abstract

Background: Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.

Methods: In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.

Results: Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.

Conclusions: At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

Figure 1. Findings on Optical Coherence Tomography

Panel A shows an optical coherence tomogram of a normal retina, with a multilayered neurosensory retina, normal central foveal depression, and retinal pigment epithelial (RPE) cell layer. Panel B shows the results for a typical study patient at baseline, with a marked increase in retinal thickness caused by intraretinal fluid, subretinal fluid, and sub-RPE fluid. Panel C shows a small area of intraretinal fluid, approximately equal to the median amount of fluid that was present in patients assigned to treatment as needed who did not receive treatment even though the reading-center graders identified fluid. Panel D shows the retinal thickness at 12 months in a patient treated with ranibizumab monthly. The retinal thickness, approximately equal to the mean thickness in the ranibizumab-monthly group, and the morphologic features of the retina are similar to normal retinal anatomy. Panel E shows the 12-month results for a patient who was treated with bevacizumab monthly. The retinal thickness, approximately equal to the mean for the bevacizumab-monthly group, and the morphologic features of the retina are also similar to normal retinal anatomy. Panel F shows the mean change in total retinal thickness at the fovea during the first year of follow-up.

Figure 2. Change in Visual-Acuity Score from Baseline to 1 Year

Panel A shows the mean change in the visual-acuity score during the first year of follow-up. Panel B shows differences between pairs of study groups in the mean change from baseline to 1 year in the visual-acuity score. The red vertical lines indicate means, and the gray bars 99.2% confidence intervals. Negative values reflect a greater mean increase in group 2. Confidence intervals within −5 and +5 letters (dashed vertical lines) indicate that the two groups are equivalent. Confidence intervals extending beyond the noninferiority limit of −5 letters indicate that the comparison of the two groups is inconclusive with respect to noninferiority. Panel C shows the proportions of patients in each group with a decrease of 15 letters or more, a change within 14 letters, or an increase of 15 letters or more from baseline values during the first study year.