Abstract
Purpose:
A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intraocular ranibizumab and aflibercept concentration and free vascular endothelial growth factor (VEGF) proportion.
Methods:
A time-dependent mathematical model using Wolfram Mathematica software was developed on the 12-month data from PIER, MONT BLANC, CATT, VIEW. Pharmacokinetic and affinity data for ranibizumab and aflibercept were obtained from published reports. Two alternative regimens with bimonthly ranibizumab and quarterly aflibercept were simulated.
Results:
The mathematical model showed good correlation between clinical trial data and intraocular VEGF proportion. In the fixed monthly 0.5 mg ranibizumab regimen that has been evaluated in MARINA, ANCHOR and CATT trials highest free VEGF levels stay below 1/100,000 of total VEGF. Following the quarterly administration of 0.5 mg ranibizumab (PIER study), highest free VEGF levels reach the 60% of total VEGF. In the individualized regimen studied in the MONT BLANC trial free VEGF proportion reaches 100% during the maintenance phase. The aggressive individualized regimen with 0.5 mg ranibizumab studied in the CATT trial with a simulated even distribution of injections maintains free VEGF levels constantly below 0.5% of total VEGF. Simulations of the two alternative regimens suggest that such treatment approaches maintain the free VEGF proportion under threshold levels. Free VEGF proportion remains stably below 0.5% and 0.1% with bimonthly ranibizumab and quarterly aflibercept respectively.
Conclusions:
Fixed bimonthly ranibizumab or quarterly aflibercept regimens may result in visual acuity improvement with reduced burden over treatment strategies applied in clinical trials.
Keywords: 412 age-related macular degeneration •
453 choroid: neovascularization •
561 injection