Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema. Ophthalmology 2018 Jul;125(7):1054-1063
Date
03/12/2018Pubmed ID
29525602Pubmed Central ID
PMC6568257DOI
10.1016/j.ophtha.2018.01.019Scopus ID
2-s2.0-85042941882 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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 < 0.001), and -0.30 (-0.43 to -0.18; P < 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 < 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's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.
Author List
Jampol LM, Glassman AR, Liu D, Aiello LP, Bressler NM, Duh EJ, Quaggin S, Wells JA, Wykoff CC, Diabetic Retinopathy Clinical Research NetworkAuthors
Baseer Ahmad MD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinThomas B. Connor MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsBevacizumab
Diabetic Retinopathy
Enzyme-Linked Immunosorbent Assay
Female
Follow-Up Studies
Humans
Intravitreal Injections
Macular Edema
Male
Middle Aged
Ranibizumab
Receptors, Vascular Endothelial Growth Factor
Recombinant Fusion Proteins
Retreatment
Tomography, Optical Coherence
Treatment Outcome
Vascular Endothelial Growth Factor A
Visual Acuity
