Real-World Dosing Intervals for Long-Acting Anti-VEGF Intravitreal Injection Therapies in nAMD and DME: Academy IRIS® Registry Analysis.

PURPOSE: To determine real-world dosing intervals for long-acting intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). METHODS: Retrospective observational cohort study in American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) patients with nAMD or DME treated with aflibercept 8 mg (aflibercept) or faricimab. Mean injection intervals during a ≤24-month period beginning 3 or 4 months after the initial injection were evaluated and descriptively contrasted with those in phase 3 clinical trials. RESULTS: The mean dosing interval was 5-8, 9-12, and ≥13 weeks in 27.5%, 45.6%, and 25.8% of aflibercept-treated patients with nAMD (n = 40,065); 27.0%, 43.4%, and 28.3% of aflibercept-treated patients with DME (n = 13,045); 40.5%, 36.1%, and 20.8% of faricimab-treated patients with nAMD (n = 132,697); and 42.2%, 31.7%, and 22.5% of faricimab-treated patients with DME (n = 39,849). Dosing intervals were consistent between treatment-naïve and previously treated patients. In aflibercept phase 3 studies, 77% (nAMD) and 89% (DME) of patients achieved a 16-week dosing interval. In faricimab phase 3 studies, 45% (nAMD) and 52% (DME) of patients achieved a 16-week dosing interval. CONCLUSION: Extension of injection intervals to 16 weeks is greatly reduced in real-world experience compared with phase 3 clinical studies. This discrepancy could be explained by protocol-mandated restrictive rescue criteria used in the registration studies, allowing injection only after vision loss and significant fluid recurrence. Current longer-acting anti-VEGF medications offer an extension to only 5-12 weeks for most patients in the real world.