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Abstract
Objective Explore relationships between systemic exposure to intravitreal aflibercept injection (IAI) and systemic pharmacodynamic effects via post hoc analyses of clinical trials of IAI for neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DME).
Methods and analysis Adults from VGFT-OD-0702.PK (n=6), VGFT-OD-0512 (n= 5), VIEW 2 (n=1204) and VIVID-DME (n=404) studies were included. Validated ELISAs were used to measure concentrations of free and bound aflibercept (reported as adjusted bound) in plasma at predefined time points in each study. Non-compartmental analysis of concentration–time data was obtained with dense sampling in VGFT-OD-0702.PK and VGFT-OD-0512. Sparse sampling was used in VIEW 2 and VIVID-DME. Blood pressure or intrarenal function changes were also investigated.
Results Following intravitreal administration, free aflibercept plasma concentrations quickly decreased once maximum concentrations were achieved at 1–3 days postdose; pharmacologically inactive adjusted bound aflibercept concentrations increased over a longer period and reached plateau 7 days postdose. Ratios of free and adjusted bound aflibercept decreased over time. There were no meaningful changes in systolic/diastolic blood pressure over the duration of each study at all systemic aflibercept exposure levels. For all treatment arms in VIEW 2, there was no clinically relevant change in mean intrarenal function from baseline at week 52. Overall, incidence of systemic adverse events in VIEW 2 and VIVID-DME was low and consistent with the known safety profile of IAI.
Conclusion IAI administration was not associated with systemic effects in patients with nAMD or DME as measured by blood pressure or intrarenal function, two known pharmacologically relevant effects of anti-vascular endothelial growth factor.
- drugs
- pharmacology
- retina
- treatment medical
- vision
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Footnotes
Contributors All authors (PKK, LK, JFK, JW, AT, OZ, RV, CA, TZ, ATD and JH) had full access to the data in the study, contributed to the concept and design of the analysis, participated in the acquisition, analysis or interpretation of the data, drafted and provided critical revision of the manuscript for intellectual content and confirmed submission of the manuscript for publication. PKK, CA, OZ, TZ, ATD and JH contributed to and provided input to the statistical analysis. PKK and JH are responsible for the overall content as guarantors of the information presented. The sponsor Bayer was involved in study design, collection, analysis and interpretation of data, writing the report and in the decision to submit the article for publication.
Funding The publication of this article was supported by Bayer.
Competing interests PKK is a consultant to Bayer and Regeneron. LK is a principal investigator for trials sponsored by Alcon, Bayer and Novartis; has also sat on advisory boards for Alcon, Allergan, Bayer, Krys, Novartis and Théa; and has received lecture fees from Alcon, Allergan, Bayer, Novartis, Théa and Zeiss. JFK is a consultant for Alcon, Alimera, Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche, Thea and Zeiss. JW is a consultant to Bayer. AT, RV and ATD are employees of Regeneron. OZ, CA, TZ and JH are employees of Bayer.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.