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Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema
Authors
Lloyd Paul Aiello
Andrew N. Antoszyk
+31 more
Uma M. Balasubramaniam
Swann J. Bojaj
Neil M. Bressler
David Browning
Loraine M. Clark
Elia J. Duh
Matt Dunlap
Sarah A. Ennis
Christina J. Fleming
Sherry L. Fredenberg
Kelly R. Gallagher
Adam R. Glassman
Autumn C. Grupp
Susannah J. Held
Jenna T. Herby
Lisa A. Jackson
Lee M. Jampol
Angella S. Karow
Kathryn Kimrey
Jeff A. Kuopus
Danni Liu
Ashley A. McClain
Donna McClain
Michael D. McOwen
Angela K. Price
Danielle Puskas
Susan Quaggin
Donna R. Styles
Lynn Watson
John A. Wells
Charles C. Wykoff
Publication date
1 July 2018
Publisher
Health Sciences Research Commons
Abstract
© 2018 American Academy of Ophthalmology Purpose: To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. Design: Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. Participants: Participants with available plasma samples (N = 436). Methods: Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. Main Outcome Measures: Changes in the natural log (ln) of plasma VEGF levels. Results: Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P \u3c 0.001), and −0.30 (−0.43 to −0.18; P \u3c 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P \u3c 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar. Conclusions: These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay\u27s ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted
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Last time updated on 17/03/2021