One-year study results from the treat-and-extend neovascular age-related macular degeneration (TREX-AMD) strategy resulted in visual and anatomic gains comparable with gains obtained with monthly dosing of intravitreal ranibizumab.
In this Phase IIIb multicenter, randomized clinical trial, 60 patients with treatment-naïve neovascular AMD and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity from 20/32 to 20/500 (Snellen equivalent) were randomized 1:2 to receive intravitreal 0.5-mg ranibizumab monthly or treat-and-extend (TREX) management. The TREX patients were treated monthly for at least three doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to strict prospective protocol. Outcomes were measured via mean ETDRS BCVA change from baseline.
At baseline, mean age was 77 years (range: 59 to 96 years), mean BCVA was 20/60 (Snellen equivalent) and mean central retinal thickness was 511 μm. Fifty-seven eyes (95 percent) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (p=0.60). The mean number of injections administered through month 12 was 13.0 for the monthly cohort and 10.1 for the TREX cohort (range: seven to 13; p<0.0001). Among TREX patients, seven (18 percent) were maximally extended, four (10 percent) demonstrated fluid at every visit and at month 12, 18 (45 percent) had achieved an extension interval of eight weeks or more; the mean maximum extension interval between injections after the first three monthly doses was 8.4 weeks (range: four to 12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24, 71 percent) were unable to extend beyond their initial maximum extension interval.
Wykoff C, Croft D, Brown D, Wang R.
Baseline VA and CRT After One Year of Anti-VEGF for DME
Comparisons of the relative effect of three anti-vascular endothelial growth factor drugs in treating diabetic macular edema suggests that for eyes with better initial visual acuity and thicker central subfield thickness, some VA outcomes may be worse in the bevacizumab group. Given small sample sizes and the exploratory nature of the analyses, the members of the Diabetic Retinopathy Clinical Research Network suggest caution is warranted when using data to guide treatment considerations for patients.
Researchers performed post hoc exploratory analyses of randomized trial data evaluating three anti-VEGF agents on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 2012 and August 2013. Treatment subgroups were based on baseline VA and CST as evaluated by OCT, with repeated 0.05 mL intravitreous injections of 2-mg aflibercept (224 eyes), 1.25 mg of bevaciumab (218 eyes) or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. Outcomes were measured at one year within the pre-specified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 μm) or thinner (250 to 399 μm) CST.
In the subgroup with the worse baseline VA (n=305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61 to 73 eyes across three treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4 and +7.6 letters in the aflibercept, bevacizumab and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31 to 42 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to one year was +9.5 letters for the aflibercept group, +5.4 letters for the bevacizumab group and +9.5 letters for the ranibizumab groups, and the VA letter score was greater than 84 (approximately 20/20) in 21 of 33 aflibercept eyes (64 percent), seven of 31 bevacizumab eyes (23 percent), and 21 of 43 ranibizumab eyes (49 percent). The adjusted differences and 95 percent confidence intervals were 39 percent (17 to 60 percent) for aflibercept vs. bevacizumab, 25 percent (5 to 46 percent) for ranibizumab vs. bevacizumab and 13 percent (-8 to 35 percent) for aflibercept vs. ranibizumab.
JAMA Ophthalmol 2016;134:2:127-134.
Wells J, Glassman A, Jampol L, Aiello L, Antoszyk A, et al.
A Cochrane Systematic Review of Avastin vs. Lucentis for Treatment of Neovascular AMD
Using results from a Cochrane Eyes and Vision Group systematic review, researchers found no important differences in effectiveness or safety between bevacizumab (Avastin) and ranibizumab (Lucentis) for neovascular age-related macular degeneration treatment, but did find a large difference in cost.
Utilizing Cochrane methods for trial selection, data extraction and data analyses, researchers included only randomized controlled trials in which the two anti-vascular endothelial growth factor agents had been compared directly; six eligible trials with 2,809 participants were identified. The primary outcome was one-year gain in best-corrected visual acuity of ≥15 letters.
The proportion of eyes that gained ≥15 letters of BCVA by one year was similar for the two agents when the same regimens were compared (risk ratio: 0.90; 95 percent confidence interval, 0.73 to 1.11). The mean change in BCVA from baseline also was similar (mean difference: -0.5 letter; 95 percent CI, -1.6 to +0.6). Other BCVA and quality of life outcomes were similar for the two agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost of bevacizumab in the two largest trials. Ocular adverse events were uncommon (<1 percent), and rates were similar for the two agents.
Solomon S, Lindsley K, Krzystolik M, Vedula S, et al.