- Email: [email protected]
Is intravitreal bevacizumab use safe for AMD?
MEDICAL ABSTRACTS Andrew S. Gurwood, O.D.
Is intravitreal bevacizumab use safe for AMD? Michels S. Is intravitreal bevacizumab (Avastin) safe? Br J Ophthalmol 2006;90:1333-4. The recent focus in the battle to arrest the visual devastation brought about by “wet” age-related macular degeneration (AMD) has been concentrated among newly developed compounds that inhibit vascular endothelial growth factors (VEGF). These naturally occurring chemical mediators, released under the stress of the AMD process, enable the production of subretinal neovascularization. The newest of the preparations developed to both prevent occurrences as well as rescue patients with preexisting lesions, is the offlabel use of intravitreal bevacizumab (Avastin Genentech, South San Francisco, California; Roche AG, Basle, Switzerland). However, the question is, is it safe? Michels, in a report published in the British Journal of Ophthalmology, documents a survey in which 70 centers from 12 countries voluntarily reported on more than 7,000 injections in more than 5,000 patients using an internet-based questionnaire within 6 months of its time of issue. The results of the safety survey found no evidence of drug-related adverse events for intravitreal bevacizumab beyond those seen in the control groups. Bevacizumab is a monoclonal antibody designed for binding all isoforms of VEGF. It has been developed primarily for cancer treatment. It is
currently approved for the treatment of metastatic colorectal cancer in combination with chemotherapy. In cancer patients, the medication is typically administered by systemic infusion at 5 mg/kg every 2 weeks serially for months. All Food and Drug Administration (FDA) warnings are relative to this patient population and this treatment regimen. The ophthalmic community commonly uses doses of 1 to 2.5 mg given intravitreally at a minimum interval of every 4 weeks. This dosage is many times less than the systemic dose required for patients with cancer. However, there are basically 3 areas of safety concerns when using intravitreal injections: 1) the route for delivering the drug, 2) the harmful intraocular effects caused by the intraocular drug dose, and 3) the potential for systemic adverse effects. Michels points out that the safety profile for the procedure of intravitreal injection itself has been well established. Further he notes that cell cultures of human retinal pigment epithelial, rat neurosensory retinal, or human microvascular endothelial cells showed no toxic effect at doses of bevacizumab above those in clinical use. He goes on to illustrate that the only dose-limiting effect reported in animals was some inflammatory reaction in the vitreous after intravitreal injections of bevacizumab reached 5 mg total. In humans, there has been no evidence of toxic ocular effects in the short term. Further, he points out that patients with neovascular AMD treated with intravitreal bevacizumab showed improved multifocal electroretinogram macular function responses and a reduction in anterior chamber cell and flare measurements,
1529-1839/07/$ -see front matter © 2007 American Optometric Association. All rights reserved.
Andrew S. Gurwood, O.D. indicating a potentially anti-inflammatory effect of the drug. Regarding the final aspect of safety, despite a drug dosage of 5 mg/kg, the only systemic adverse event reported, according to Michels, was a transient, well-controlled increase in blood pressure in some patients. Several retrospective clinical studies on intravitreal bevacizumab and a recent prospective study using 2.5 mg intravitreal bevacizumab showed no increased risk to either systemic or ocular health. Although long-term ophthalmic data are still being gathered, the international intravitreal bevacizumab safety survey has further strengthened the good short-term safety profile of off-label intravitreal bevacizumab, making its inclusion into the armamentarium of anti-VEGF agents deserving of consideration. Andrew S. Gurwood, O.D. doi:10.1016/j.optm.2006.11.004
Is intravitreal bevacizumab use safe for AMD? Michels S. Is intravitreal bevacizumab (Avastin) safe? Br J Ophthalmol 2006;90:1333-4. The recent focus in the battle to arrest the visual devastation brought about by “wet” age-related macular degeneration (AMD) has been concentrated among newly developed compounds that inhibit vascular endothelial growth factors (VEGF). These naturally occurring chemical mediators, released under the stress of the AMD process, enable the production of subretinal neovascularization. The newest of the preparations developed to both prevent occurrences as well as rescue patients with preexisting lesions, is the offlabel use of intravitreal bevacizumab (Avastin Genentech, South San Francisco, California; Roche AG, Basle, Switzerland). However, the question is, is it safe? Michels, in a report published in the British Journal of Ophthalmology, documents a survey in which 70 centers from 12 countries voluntarily reported on more than 7,000 injections in more than 5,000 patients using an internet-based questionnaire within 6 months of its time of issue. The results of the safety survey found no evidence of drug-related adverse events for intravitreal bevacizumab beyond those seen in the control groups. Bevacizumab is a monoclonal antibody designed for binding all isoforms of VEGF. It has been developed primarily for cancer treatment. It is
currently approved for the treatment of metastatic colorectal cancer in combination with chemotherapy. In cancer patients, the medication is typically administered by systemic infusion at 5 mg/kg every 2 weeks serially for months. All Food and Drug Administration (FDA) warnings are relative to this patient population and this treatment regimen. The ophthalmic community commonly uses doses of 1 to 2.5 mg given intravitreally at a minimum interval of every 4 weeks. This dosage is many times less than the systemic dose required for patients with cancer. However, there are basically 3 areas of safety concerns when using intravitreal injections: 1) the route for delivering the drug, 2) the harmful intraocular effects caused by the intraocular drug dose, and 3) the potential for systemic adverse effects. Michels points out that the safety profile for the procedure of intravitreal injection itself has been well established. Further he notes that cell cultures of human retinal pigment epithelial, rat neurosensory retinal, or human microvascular endothelial cells showed no toxic effect at doses of bevacizumab above those in clinical use. He goes on to illustrate that the only dose-limiting effect reported in animals was some inflammatory reaction in the vitreous after intravitreal injections of bevacizumab reached 5 mg total. In humans, there has been no evidence of toxic ocular effects in the short term. Further, he points out that patients with neovascular AMD treated with intravitreal bevacizumab showed improved multifocal electroretinogram macular function responses and a reduction in anterior chamber cell and flare measurements,
1529-1839/07/$ -see front matter © 2007 American Optometric Association. All rights reserved.
Andrew S. Gurwood, O.D. indicating a potentially anti-inflammatory effect of the drug. Regarding the final aspect of safety, despite a drug dosage of 5 mg/kg, the only systemic adverse event reported, according to Michels, was a transient, well-controlled increase in blood pressure in some patients. Several retrospective clinical studies on intravitreal bevacizumab and a recent prospective study using 2.5 mg intravitreal bevacizumab showed no increased risk to either systemic or ocular health. Although long-term ophthalmic data are still being gathered, the international intravitreal bevacizumab safety survey has further strengthened the good short-term safety profile of off-label intravitreal bevacizumab, making its inclusion into the armamentarium of anti-VEGF agents deserving of consideration. Andrew S. Gurwood, O.D. doi:10.1016/j.optm.2006.11.004