Comparing Treatments for Wet Age-Related Macular Degeneration
Report from the annual ARVO (Association for Research in Vision and Ophthalmology) meeting
May 6, 2011 - Lucentis and Avastin are two drugs currently used to treat wet age-related macular degeneration (wet AMD). Both are injected into the eye. Lucentis (generic name: ranibizumab) was developed specifically to treat wet AMD, and has been studied in several major clinical trials for wet AMD with excellent results. Avastin (generic name: bevacizumab) was developed as a treatment for colorectal cancer, but is also frequently used “off-label” to treat wet AMD (see sidebar).
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What does off-label mean? To be approved and licensed in Canada, a pharmaceutical company must show that its product is effective in a series of carefully-regulated clinical trials. However, sometimes once a drug is in use, doctors will notice that it also has other benefits. For example, some anti-depressant drugs seem to relieve pain and are prescribed for that purpose. Another example is prescribing a drug for a child when it has only been tested in adults. In these situations, because the drug has been approved in Canada, the doctor can legally prescribe it. They have some information about its safety from the initial approval process, but usually only reports from other doctors about its benefits. This drug is not licensed for this new treatment purpose, instead it is used "off-label." In the case of Lucentis and Avastin, Lucentis is a drug licensed for wet AMD, while Avastin is used off-label. Most often drugs are used off-label because there are no other approved treatment options. However in the case of Lucentis and Avastin, cost is a consideration because Avastin is much less expensive. |
These two agents are being compared in the CATT study (Comparison of AMD Treatments Trial). Findings from the first year of the trial were published this month in the New England Journal of Medicine. These findings, as well as several studies presented at ARVO, have made the risks and benefits of these drugs a topic of renewed conversation in the medical community.
CATT is planned to run for two years and includes just over 1200 people receiving treatment for wet AMD. It is comparing the outcomes for people receiving monthly injections of Avastin to those receiving monthly injections of Lucentis. It is also looking at the outcomes for using both drugs prescribed as needed, rather than on a rigid monthly schedule. The recently released results show that after one year there is no difference in effectiveness between monthly Avastin and monthly Lucentis. Lucentis was also equally effective when used as needed, although Avastin was not as effective when used this way.
CATT may also offer some information about the relative safety of the two drugs, but at this point, the CATT investigators say these safety issues need further study. While there were no clear differences in the CATT study in deaths or in any particular type of illness between people receiving different treatments, people receiving Avastin were more likely to be hospitalized or have other serious illnesses than people taking Lucentis (24% versus 19% in this population of seniors). However, at the moment, there is no obvious causal link between Avastin treatment and these non-eye-related illnesses.
Other presentations made at ARVO looked further into the safety issues involved.
One of these, conducted by a team led by Dr. Emily Gower of John Hopkins University, involved a retrospective review of the records of nearly 78,000 Medicare patients in the United States. These patients were being treated for wet AMD with either Lucentis or Avastin. The research team found an 11% higher death rate from all causes, and a 47% higher risk of hemorrhagic stroke, amongst those taking Avastin compared to Lucentis. Hemorrhagic strokes occur because of a weakening of blood vessel walls; this might be associated with lower levels of VEGF growth factors in the body (both Lucentis and Avastin are anti-VEGF drugs), or unknown factors, unrelated to the treatment for AMD. There were no differences in the rates of heart attacks or other types of strokes between the two groups.
This study also found that people receiving Avastin were 80% more likely than people receiving Lucentis to have inflammation in the eye after treatment. This could happen because Avastin is sold in a single bottle; thus the physician must remove doses for each patient, one after another, increasing the risk of contamination. Lucentis, in contrast, is packaged in individual doses. (In the CATT study, individual doses of Avastin were made specifically for the trial.) Conversely, people receiving Lucentis were 19% more likely than people receiving Avastin to be diagnosed with glaucoma in the period after the trial, perhaps because the label on the Lucentis package specifically directed physicians to check the pressure in the eye after each injection.
It is often necessary to look at a very large group of people to observe differences in risks between two treatments. This study involved the largest group of AMD patients ever studied, but as Dr. Gower and her team note, this evidence comes from examining the past treatment records of unselected patients, not from comparing patient groups that have been carefully selected to be similar in medical history, treatment and follow-up. Other factors could be involved in these findings, such as different rates of smoking in the Avastin and Lucentis treatment groups. Additional trials now underway in Europe may help to clarify these issues. For now, however, individuals being treated for wet AMD may want to discuss the benefits and risks of their current treatments with their eye doctor.
ARVO Presentation
Adverse Event Rates Following Intravitreal Injection of Avastin or Lucentis for Treating Age-Related Macular Degeneration. Presented Tuesday May 3, 2011. Emily W. Gower, Sandra Cassard, Laura Chu, Rohit Varma, Ronald Klein.