The anti-vascular endothelial growth factor drugs ranibizumab and aflibercept, used to treat vision loss from diabetic macular edema (DME), and approximately 20 to 30 times more expensive than bevacizumab, are not cost-effective for treatment of DME compared to bevacizumab unless their prices decrease substantially, according to a study published online by JAMA Ophthalmology. Anti-vascular endothelial growth factor (VEGF) medicines have revolutionized DME treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year, aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. On the basis of 2015 costs, aflibercept was $1,850, ranibizumab, $1,170, and repackaged (compounded) bevacizumab, approximately $60 per dose. Considering that these medicines may be given 9 to 11 times in the first year of treatment and, on average, 17 times during 5 years, total costs can be substantial. In 2010, when these intravitreous agents were being used predominantly for age-related macular degeneration, ophthalmologic use of VEGF therapy cost approximately $2 billion or one-sixth of the entire Medicare Part B drug budget. In 2013, Medicare Part B expenditures for aflibercept and ranibizumab alone totaled $2.5 billion. “From a societal perspective, bevacizumab as first-line therapy for DME would confer the greatest value, along with substantial cost savings vs the other agents. One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10-year cost-effectiveness results. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results,” the researchers write.
JAMA Ophthalmol. Published online June 9, 2016.doi:10.1001/jamaophthalmol.2016.1669
Comment from Dr. Chous M.A., O.D. (advisory board): This issue has been brewing a long time, given the widespread use of these agents for both neovascular age-related macular degeneration (“wet” AMD) and now diabetes-related eye disease. Ranibizumab and aflibercept are the only two FDA drugs approved for diabetic macular edema (DME) and AMD, so many providers are reticent to use bevacizumab off-label out of liability concern. Two-year data from DRCR.net Protocol T, which compared all three agents head-to-head, showed no statistically significant difference in vision between aflibercept and ranibizumab, but aflibercept was statistically significantly better than bevacizumab (by a few letters on the eye chart). Two other things to note are that (1) there were more thromboembolic events (2.4 X APTC events) with ranibizumab, though events were few; (2) some patients who do not respond to Avastin (bevacizumab) do have a better response to one of the more expensive agents. My view is that patients should most often be started on the less expensive agent and switched to one of the more expensive agents only if there is demonstrated poor efficacy.