Research, led by scientists at the Department of Ophthalmology, Medical University Innsbruck, Austria, has demonstrated a significant increase in systemic levels of placental growth factor (PlGF) following intravitreal aflibercept (Eylea) treatment. If representative across larger numbers of patients the finding may have implications for optimizing clinical outcomes in age related macular degeneration. Although the total number of patients tested in the study was relatively small, no statistically significant increase in plasma PlGF levels was reported with injections of ranibizumab (Lucentis) or bevacizumab (Avastin). In a publication of the results (IOVS, DOI:10.1167/iovs.15-16686), the researchers highlighted that the work was not supported by any specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
The Austrian research had tested 19 patients treated with intravitreal aflibercept, 19 with ranibizumab, and 18 with bevacizumab, representing a total of 56 AMD patients, randomized to one or other treatment group. PlGF cytokine levels were measured by ELISA prior to anti-VEGF injections and then again 7 days and 1 month following drug administration. The results of the study showed that median PlGF plasma concentrations at baseline was <12.0 pg/mL in age and sex-matched controls as well as in each of the three anti-VEGF treatment arms prior to treatment. Following intravitreal aflibercept injection, an increase in systemic PlGF was recorded in all treated patients, 38.0 [31.0–44.0] pg/mL after 1 week [P<0.001] and 16.0 [0.0–19.0] pg/mL [P=0.005] after 4 weeks. In contrast, the researchers reported no significant effects on plasma PlGF concentrations in ranibizumab or bevacizumab treated patients.
In analyzing the results the researchers highlighted that aflibercept binds VEGF-A with approximately 100-fold higher binding affinity than either ranibizumab or bevacizumab, and, as a result, aflibercept is understood to neutralize VEGF-A with greater potency than other anti-VEGF compounds. The strength of such anti-angiogenic treatment however may promote a host counter-regulatory response that the authors believe “could be of translational relevance for the clinical outcomes in treatment of neovascular AMD”. The researchers concluded their study by commenting that, “the upregulation and increased secretion of PlGF into circulation upon intravitreal administration of aflibercept could potentially exert a countervailing trophic effect on neovascular tissue, and, thus, reduce the therapeutic effect of VEGF inhibition.”