Pro re Nata versus Bimonthly Regimen in Exudative AMD Treated with Aflibercept: 1-year Results

Abstract

Age-Related Macular Degeneration (ANCHOR) (4), and A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or without Classic CNV Secondary to Age-Related Macular Degeneration (PIER) (5) have demonstrated the efficacy of monthly ranibizumab injections. Ophthalmologists have been able to reduce the number of injections based on the results of the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with Intraocular Ranibizumab (PRONTO) (6) study using a pro re nata (PRN) regimen. Pro re nata has been demonstrated to be as efficient as monthly injections in at least 2 randomized studies: Comparison of Age-related Macular Degeneration Treatment Trial (CATT) (7) and Alternative Treatments to Inhibit VEGF in Age-related Choroidal Neovascularization (IVAN) (8). In 2011, the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies (9) demonstrated that aflibercept could be injected bimonthly for 1 year with results as good as monthly ranibizumab injections. However, few studies have compared the PRN and the fixed bimonthly regimens. Only one recent study reported the effects of these 2 regimens in cases of a switch from ranibizumab to aflibercept in recurrent nAMD. In this study, the bimonthly protocol used after the switch seemed more efficient than PRN usage (10).

Pro re nata versus fixed aflibercept regimen for neovascular age-related macular degeneration: a systematic review and meta-analysis

“…Mori et al [13], Veritti et al [14], and Weber et al [12] does not report difference in mean participant age, while Keppi et al [11], although does not report any p-value, have slightly older mean age in the PRN group compared to the bimonthly group (85.27 (range: 62-93) vs 78.47 (range: 61-95)). There was no sensitivity analysis in all the studies for interaction with age.…”

“…The most common reason for study exclusion were wrong outcome measurement, comparisons, and intervention. The four selected articles for meta-analyses synthesis were consisted of 3 controlled trials [17,28,29] and one retrospective cohort study [11].…”

“…Study characteristics are summarized in Table 1. Two studies were conducted in France [11,12], one study was conducted in Japan [13], and one study was conducted in Italy [14]. Treatment groups were PRN or as needed aflibercept injection, whereas for the fixed group, all studies followed the dosage that is instructed on the label (one 2 mg aflibercept injection every 2 months).…”

“…We assessed high risk of bias on the selection domain in Veritti et al [14] and Weber et al [12] due to the absence of patient randomization and the concealment of patient allocation. As the only retrospective study in this review, Keppi et al [11] acquired 8 scores on the Newcastle-Ottawa Scale, which means low risk of bias.…”

“…The forest plot resulted in no heterogeneity between the included studies (I 2 = 0%, p < 0.00001). The first sensitivity analysis was conducted by excluding the only retrospective study in this review [11]. The adjusted pooled SMD was 0.52 (95% CI 0.32-0.72) (Additional file 1: Figure S1) which favored fixed aflibercept regimen.…”