TY - JOUR
T1 - Safety Implications of Vascular Endothelial Growth Factor Blockade for Subjects Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Therapies
AU - Csaky, Karl
AU - Do, Diana V.
N1 - Funding Information:
This study was supported by a research funding from Genentech Inc, South San Francisco, California (Dr Do). Dr Csaky is a consultant for Genentech Inc. Both authors were involved in design and conduct of study; collection of data; management, analysis, and interpretation of data; and preparation, review, and approval of manuscript.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/11
Y1 - 2009/11
N2 - Purpose: To evaluate potential safety risks associated with nonspecific inhibition of vascular endothelial growth factor (VEGF). Design: A perspective, reviewing the current literature. Methods: Herein, we discuss the systemic safety of VEGF-targeted therapies, address safety issues for VEGF-targeted therapies in neovascular age-related macular degeneration, and propose the consideration of methods for identifying low rate systemic safety signals from patients treated with these agents. Results: Several prospective, randomized clinical trials have demonstrated that intravitreal anti-VEGF therapies generally are well tolerated. However, within these trials, there is some circumstantial evidence that links systemic VEGF inhibition to systemic adverse events, particularly systemic thromboembolic events. Because all of the intravitreal anti-VEGF agents have been associated with detectable levels in the systemic circulation, there is a scientific rationale for the occurrence of potential systemic adverse events. However, if safety issues are present, they occur at very low rates and may go undetected in controlled clinical trials of premarketed drugs. Conclusions: We propose that highly sensitive methodologies be put into place for identifying low rate safety signals, including postmarketing clinical trials, chart reviews, electronic medical records, and various national and international registries and databases, to evaluate the systemic safety of antiangiogenic agents in ocular diseases such as neovascular age-related macular degeneration.
AB - Purpose: To evaluate potential safety risks associated with nonspecific inhibition of vascular endothelial growth factor (VEGF). Design: A perspective, reviewing the current literature. Methods: Herein, we discuss the systemic safety of VEGF-targeted therapies, address safety issues for VEGF-targeted therapies in neovascular age-related macular degeneration, and propose the consideration of methods for identifying low rate systemic safety signals from patients treated with these agents. Results: Several prospective, randomized clinical trials have demonstrated that intravitreal anti-VEGF therapies generally are well tolerated. However, within these trials, there is some circumstantial evidence that links systemic VEGF inhibition to systemic adverse events, particularly systemic thromboembolic events. Because all of the intravitreal anti-VEGF agents have been associated with detectable levels in the systemic circulation, there is a scientific rationale for the occurrence of potential systemic adverse events. However, if safety issues are present, they occur at very low rates and may go undetected in controlled clinical trials of premarketed drugs. Conclusions: We propose that highly sensitive methodologies be put into place for identifying low rate safety signals, including postmarketing clinical trials, chart reviews, electronic medical records, and various national and international registries and databases, to evaluate the systemic safety of antiangiogenic agents in ocular diseases such as neovascular age-related macular degeneration.
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U2 - 10.1016/j.ajo.2009.06.014
DO - 10.1016/j.ajo.2009.06.014
M3 - Article
C2 - 19712924
AN - SCOPUS:70350575734
SN - 0002-9394
VL - 148
SP - 647
EP - 656
JO - American journal of ophthalmology
JF - American journal of ophthalmology
IS - 5
ER -