Anti-Vascular Endothelial Growth Factor Drugs for the Treatment of Retinal Conditions: A Review of the Safety [Internet]

Excerpt

Retinal conditions, such as age related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and choroidal neovascularization due to pathologic myopia (CNV due to PM) are an important public health concern that threatens the vision of millions of patients in Canada. The mechanism of these conditions involve the new formation of blood vessels in the retina that eventually leads to loss of vision. Anti-vascular endothelial growth factor (Anti-VEGF) inhibits this growth and allows the restoration of vision. Currently in Canada, two licensed anti-VEGF agents are available in the market; ranibizumab and aflibercept. Bevacizumab, on the other hand, has been developed as an anti-cancer drug. However, its close molecular resemblance to ranibizumab and identical mechanism of action has made it a widely used option, especially in environments that are strained on health resources.^,

However, despite the wide use of bevacizumab for retinal conditions, and the availability of several high-quality randomized controlled trials for its efficacy, Bevacizumab still lacks a Health Canada review for retinal indications. The bevacizumab product monograph carries a warning regarding the intravitreal use of bevacizumab, citing increased risk of ophthalmic complications. In addition, the intravenous use of bevacizumab in cancer patients is often associated with increased risk of thromboembolic events (e.g. stroke).

The CADTH therapeutic review titled “Anti–Vascular Endothelial Growth Factor Drugs for the Treatment of Retinal Conditions” established that the efficacy of bevacizumab is not different than ranibizumab or aflibercept, and did not observe any signals indicating issues regarding bevacizumab comparative safety. However, the CADTH recommendation report for the therapeutic review identifies the lack of large randomized trials powered to detect differences in harms outcomes as a research gap. The statistical power required to detect a difference in harms outcome can make a randomized clinical trial prohibitive. A review of available evidence regarding safety of bevacizumab from real-world evidence is of high clinical value, as it represents a useful tool for identifying any potential issues regarding the safety of bevacizumab for use in treating retinal conditions. A summary and critical appraisal of studies regarding bevacizumab safety, contrasted with those of ranibizumab and aflibercept, for the treatment of retinal conditions would allow for a more informed and evidence-based policy and clinical decision process.