Different aflibercept regimens for wet age-related macular degeneration: A systematic review and network meta-analysis

BACKGROUND: Intravitreal aflibercept injection for wet age-related macular degeneration (AMD) was initially approved with a regimen consisting of three monthly loading doses followed by maintenance doses every 8 weeks. Alternative regimens with a reduced treatment burden have been explored. The treat-and-extend (TAE) regimen involves gradually extending the treatment interval in accordance with disease activity, and the pro re nata (PRN) regimen involves administering injections only when signs of disease activity are observed during follow-up visits. This study evaluated these alternative regimens aimed at reducing treatment burden in real-world clinical practice. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs). A random-effects model was adopted for network meta-analysis. Results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Methodological quality of the included RCTs was assessed using the Cochrane risk-of-bias 2.0 tool. RESULTS: Seven RCTs (1,683 patients with wet AMD) were included in the network meta-analysis. No significant interregimen differences were observed in visual acuity or central retinal thickness. The TAE and PRN regimens required significantly fewer injections than did bimonthly and monthly regimens, respectively (TAE vs. bimonthly: SMD -1.091, 95% CI -2.030 to -0.153; TAE vs. monthly: SMD -3.024, 95% CI -4.584 to -1.465; PRN vs. Bimonthly: SMD -1.919, 95% CI -3.307 to -0.532; PRN vs. Monthly: SMD -3.852, 95% CI -5.717 to -1.988). However, injection count did not differ significantly between the TAE and PRN regimens (TAE vs. PRN: SMD 0.828, 95% CI -0.847 to 2.503). Nonetheless, the TAE regimen was associated with fewer clinic visits than the PRN regimen. CONCLUSION: The TAE regimen maintains efficacy while reducing treatment burden in patients with wet AMD receiving intravitreal aflibercept.