Intravitreal ranibizumab (Lucentis®) and conbercept (Langmu®) in regulation of plasma vascular endothelial growth factor levels for neovascular age-related macular degeneration: a pilot phase IV, randomized, open label, controlled trial

Poster Details

First Author: M.Zhang CHINA

Co Author(s):    X. Tan   Y. Gao   J. Zhang   S. Lv                    

Abstract Details


Anti-vascular endothelial growth factor (anti-VEGF) agents are the first effective treatments for neovascular age-related macular degeneration (nAMD). Ranibizumab and conbercept were approved by China Food and Drug Administration (CFDA) for nAMD treatment, but there is no head to head study to show their effects on systemic VEGF suppression during 3 loading doses. As systemic VEGF suppression may cause some systemic adverse effects, such as cerebrovascular events. The purpose of the study is to evaluate plasma VEGF levels after intravitreal injections of ranibizumab and conbercept in nAMD patients, and intend to provide more safety relevant data for clinical medicine postmarket.


West China Hospital, Chengdu, Sichuan, China


This is a pilot phase IV, prospective, open label study. Patients aged >50 years old with subfoveal or juxtafoveal CNV secondary to nAMD and with a best corrected visual acuity (BCVA) score between 24—73 letters as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart were enrolled. Twelve patients were randomized into the ranibizumab group (n=6) or the conbercept group (n=6). Patients received 0.5mg ranibizumab and 0.5mg conbercept intravitreal injections once per month for three consecutive months in the ranibizumab group and the conbercept group, respectively. Plasma VEGF levels were measured at pre-dose, 3 hours post-injections and days 1, 3, 7 and 28 following doses 1 and 3. Plasma VEGF concentrations were measured by a blinded laboratory using Quantikine® ELISA kits. Descriptive statistics were used to summarize the results.


The baseline plasma VEGF level of the ranibizumab group was 31.40 ± 6.38 pg/mL, whereas the conbercept group was 44.92 ± 21.18 pg/mL. In the conbercept group, VEGF levels decreased to 16.32 ± 11.69 pg/mL 3 hours after the first injection, and stayed below baseline until 4 weeks when it returned to 24.59 ± 13.60 pg/mL. In comparison, in the ranibizumab VEGF levels slightly decreased to 30.96 ± 19.98 pg/mL and remained relatively constant through the treatment period, and VEGF level was 27.09 ± 13.24 pg/mL at 4 week. Similar change of VEGF levels occurred after the third dose of injection, plasma VEGF decreased from 35.52±19.23pg/mL to 5.72±2.17pg/mL 3 hours after third injection in conbercept group, while 36.25±11.86pg/mL to 34.38±12.77pg/mL in ranibizumab group.


Intravitreal conbercept caused rapid reduction in plasma VEGF but gradually returned to baseline until 4 week, while plasma VEGF levels appeared more stable with ranibizumab treatment. A larger sample size is needed to further characterize the change of systemic VEGF change after conbercept and ranibizumab intravitreal treatment, and the relevance of these findings to systemic safety.

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