4CPS-233 Effect of high-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration: comparison of real-world outcomes with pharmacokinetic model

<h3>Background and Importance</h3> Aflibercept (AFLI) is indicated for the treatment of exudative neovascular age macular degeneration (nAMD), by intravitreal injection (IVI). The intraocular bioavailability of AFLI follows a logarithmic distribution, and it will be effective as long as its ocular concentration saturates VEGF receptors. Below this threshold, free VEGF promotes exudation and irreversible tissue damage. Recently, a higher dose of AFLI (8mg/0.07mL, AFLI8) was approved compared to 2mg/0.05mL (AFLI2). <h3>Aim and Objectives</h3> To evaluate the correlation between the theoretical pharmacokinetic rationale for the high-dose AFLI8 regimen and its effectiveness in patients with nAMD. <h3>Material and Methods</h3> Retrospective study of patients with nAMD with subfoveal type 1 macular neovascularisation who were switched from AFLI2 to AFLI8. Inclusion criteria were long-term treatment (≥6 months) with persistence of retinal fluid detected 4 weeks after the last AFLI2 IVI and one response assessment 2 weeks after AFLI8 IVI. Best corrected visual acuity (BCVA) was measured using Snellen chart and all patients were imaged with spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT-Angiography (OCTA). A time-dependent mathematical model was developed, using Python, to calculate AFLI concentrations with AFLI2 and AFLI8, and compared with clinical outcomes. <h3>Results</h3> 20 eyes, from 20 patients, were analysed. Before switch, median number of IVIs was eight, mean BCVA was 0.22 logMAR and mean Central Retinal Thickness (CRT)=283.5µm. Comparison between absolute intravitreal theoretical values (AFLI2 vs AFLI8) showed a difference of 18 days (p=0.042), i.e. the estimated intravitreal dosage at 14 days of AFLI2 was expected to be the same at 32 days after AFLI8. Comparison of clinical outcomes between 2 week/AFLI2 vs 4 week/AFLI8 interval showed absence of differences between BCVA (p=0.317) and CRT (p=0.779). Although no significant differences were found, clinically there was a reduction in CRT (p=0.128) between the 1st IVI (283 µm) and the 3rd IVI (255 µm) of ALFI8. <h3>Conclusion and Relevance</h3> Understanding of the ocular pharmacokinetics of AFLI may facilitate the identification of patients who can benefit from a transition to a higher dose and predict the feasibility of extending the dosing interval. A theoretical increment of 18 days predicted by the pharmacokinetic model seemed to correspond to clinical outcomes evaluated in this study. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest