Vascular endothelial growth factor plasma levels before and after treatment of neovascular age‐related macular degeneration with bevacizumab or ranibizumab

Abstract

. Purpose: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age‐related macular degeneration (AMD). Methods: Forty‐three patients with exudative AMD and 19 age‐ and sex‐matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4‐weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. Results: At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty‐eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab‐treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab‐treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. Conclusions: Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time‐point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.

Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

“…However, by measuring serum rather than plasma VEGF, a significant portion of the VEGF measured would include VEGF released by platelets, which artificially increases systemic levels of VEGF measured and may mask subtle changes in VEGF levels. 7,18 Subsequent studies measuring plasma VEGF have also reported significant decreases in plasma VEGF following intravitreal bevacizumab, and non-statistically significant decreases in plasma VEGF following intravitreal ranibizumab, [5][6][7][8][9] which supports the IVAN findings, but remains at odds with data from the oncology literature.…”

“…1 Different anti-VEGF agents also have different molecular structures, different transmissibility across the blood-retinal barrier, and different systemic half-lives, so could potentially have different effects on systemic VEGF levels. 1,[6][7][8][9] Ranibizumab is a recombinantly produced, humanized monoclonal antibody fragment (Fab) designed for intraocular use that binds and inhibits all biologically active isoforms of human VEGF. 10 Its transmissibility across the blood-retinal barrier is lower than that of fulllength molecules, but systemic bioavailability of ranibizumab has been reported post intravitreal injections.…”

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

“…Aflibercept, similar to bevacizumab induces a significant reduction of VEGF in the blood plasma persisting throughout the entire observational period of our study (Matsuyama et al 2010;Carneiro et al 2012;Zehetner et al 2013;Wang et al 2014). VEGF is a multifunctional cytokine that regulates biological functions in endothelial cells in adult vasculature.…”

“…It has been shown that bevacizumab significantly reduces systemic VEGF levels after intravitreal injection (Matsuyama et al 2010;Carneiro et al 2012;Chakravarthy et al 2012;Zehetner et al 2013). Aflibercept contains a Fc fragment like bevacizumab and therefore interacts with the neonatal Fc receptor (FcRn).…”

Evaluation of the clinical effectiveness of fluocinolone acetonide 190 µg intravitreal implant in diabetic macular edema: a comparison between study and fellow eyes

“…Due to the low level of systemic absorption, the effect of the FAc implant on the fellow eye is thought to be low. However, bevacizumab has been reported to significantly reduce the level of VEGF in the blood plasma for up to 28 days post injection in people with DME and age-related macular degeneration 28,29 . Furthermore, studies have shown that anti-VEGF therapy administered unilaterally can have beneficial effects in the contralateral eye of people with bilateral DME 30 , age-related diabetic macular degeneration 31 , proliferative diabetic retinopathy 32 , or uveitis-related cystoid macular edema 33 .…”