Bevacizumab (Avastin, Genentech) injections do not raise the risk for endophthalmitis compared with injections of its manufacturer's more costly counterpart, ranibizumab (Lucentis), according to a retrospective study published online August 13 in JAMA Ophthalmology.
The analysis, which was based on insurance claims, was conducted in response to case reports of bevacizumab-related endophthalmitis, which led the US Food and Drug Administration (FDA) to propose significant restrictions on the drug's use for retinal diseases.
"Our analysis of a national dataset shows that the risk for endophthalmitis is no higher with Avastin and hints that there may actually be a lower endophthalmitis risk compared to Lucentis, so the proposed FDA restrictions for Avastin might have the unintended consequence of increasing the infection risk for patients," said senior author Brian L. VanderBeek, MD, MPH, an assistant professor of ophthalmology at Perelman School of Medicine, University of Pennsylvania, Philadelphia, in a university media release.
After the antivascular endothelial growth factor (VEGF) drug was approved by the FDA in 2004 for inhibiting angiogenesis in colorectal cancers, ophthalmologists began using it off-label to treat VEGF-related eye conditions such as wet macular degeneration. Compounding pharmacies began repackaging the cancer drug into smaller doses suitable for intraocular injection at as little as $50 a dose.
Its manufacturer, Genentech, then developed an eye-specific anti-VEGF antibody, ranibizumab anti-VEGF, costing as much as $2000 a dose and moved to block the sale of bevacizumab to compounding pharmacies. It backtracked in response to protests from ophthalmologists, according to the Penn release.
The FDA's proposal to restrict bevacizumab’s ophthalmological use to within 5 days of repackaging would prevent most eye-related applications. "Compounding pharmacies require 14 days after repackaging just for sterility testing, and without this critical step, ophthalmologists will lack confidence in the safety of the repackaged Avastin and [be] unlikely to use it," said Dr VanderBeek.
Using a cohort from the claims data of a large national insurance company, the Penn researchers analyzed 296,565 intravitreal injections of bevacizumab in 51,116 patients and 87,245 injections of ranibizumab in 7496 patients from 2005 to 2012. They found a total of 71 cases of endophthalmitis (49 for bevacizumab and 22 for ranibizumab). The rate of the complication in this dataset was very low, at 0.017% for bevacizumab (95% confidence interval, 0.012% - 0.021%), and still low but slightly higher, at 0.025% (95% confidence interval, 0.015% - 0.036%) for ranibizumab.
After controlling for age, race, sex, injection-related diagnosis, and year of injection, the lack of significant association with endophthalmitis after bevacizumab injection remained (odds ratio, 0.66; 95% confidence interval, 0.39 - 1.09; P = .11).
The data suggest that on a nationwide basis, bevacizumab repackaged by compounding pharmacies involves no greater endophthalmitis risk than Lucentis packaged by its manufacturer, the authors state, adding that the findings support the American Academy of Ophthalmology's opposition to the proposed FDA regulations.
"Although contamination of compounded medications is an issue that needs constant vigilance, this study supports the idea that tight adherence to current compounding protocols and practice standards can ensure the safe use of bevacizumab in ophthalmic practice without additional regulation," they write.
This study was supported by the National Institutes of Health, Research to Prevent Blindness, and the Paul and Evanina Mackall Foundation. The authors have disclosed no relevant financial relationships.
JAMA Ophthalmol. Published online August 13, 2015. Full text
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Cite this: Endophthalmitis Risk No Greater With Avastin Than Lucentis - Medscape - Aug 17, 2015.