While several treatment modalities exist for macular degeneration—such as
photocoagulation, photodynamic therapy, and Macugen® (pegaptanib sodium, Eyetech Inc.)—they have been almost completely replaced by anti-vascular endothelial growth factor (VEGF) therapies. Lucentis® (ranibizumab, Genentech) has been touted as having tremendous success for wet age-related macular degeneration (AMD); however, prior to its approval, many physicians grew accustomed to using Avastin® (bevacizumab, Genentech) in an off-label format. Once Lucentis became FDA approved, many questions arose, such as: Is Lucentis more effective than Avastin? If so, is the additional cost worth the benefit? Does one medication have more risks than the other? The Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT) were initiated to answer many of these questions.
For this multicenter study, patients were randomly selected to receive either Lucentis or Avastin as either monthly or "as-needed" injections. Inclusion criteria were: age >50, prior untreated choroidal neovascularization due to AMD, and visual acuity between 20/25 and 20/320. To establish the presence of active choroidal neovascularization, fluorescein angiography and optical coherence tomography (OCT) were performed. Monthly injection patients were evaluated and treated every 28 days, while as-needed treatment patients were injected only if signs of active neovascularization were present. Time-domain optical coherence tomography was performed with the use of macular thickness maps and fast macular thickness maps. Signs of active neovascularization were defined as fluid on OCT, new or persistent hemorrhage, decreased visual acuity compared to the previous examination, or dye leakage. Patients in the Lucentis group received 0.50 mg (in 0.05 ml solution), while those in the Avastin group were administered 1.25 mg (in 0.05 ml solution).
In brief, patients who received Avastin had visual improvement equal to those who were given Lucentis, and patients who received as-needed therapy seemed to do as well as those given monthly injections. There are, of course, several caveats: While visual acuity was equal between groups, Lucentis patients had a greater overall decrease in central retinal thickness. Also, there appeared to be a higher incidence of hospitalizations for Avastin patients. While risk such as hemorrhagic stroke may be somewhat higher for patients receiving Avastin, it is important to note that the Avastin patients appeared slightly older than the Lucentis patients, and this may have been a confounding variable. Nevertheless, there seems to be good evidence that for the majority of patients, as-needed dosing of Avastin may be equally efficacious as monthly Lucentis. Of course, longer-term data are needed.
What does this mean for patients, physicians, and health care as a whole? Simply put, access to AMD therapy and overall financial burden to society may be greatly improved by off-label use of a medication. Considering the difference between a $2000/injection Lucentis (monthly) and $50/injection Avastin (as needed), the savings are staggering, particularly in light of the epidemic of macular degeneration that will occur with the aging of the Baby Boom Generation. For now, ophthalmologists can take comfort in the fact that they are providing quality care to their patients because the less expensive, alternative medication is by no means inferior.