Eyeworld

EW NEWS & OPINION 21 P atients with age-related macular degeneration (ARMD) who are treated with newer medications such as bevacizumab (Avastin, Genentech, San Francisco, Calif.) or ranibizumab (Lucentis, Genentech) are at no greater in- creased risk of mortality, heart at- tack, stroke, or bleeding than those who receive photodynamic therapy (PDT) or pegaptanib (Macugen, Eyetech, Palm Beach Gardens, Fla.), according to Lesley H. Curtis, Ph.D., associate professor of medicine, Duke University School of Medicine, Durham, N.C. Study results on this appeared in the October 2010 issue of Archives of Ophthalmology. Investigators were spurred to look into possible associations be- tween different ARMD therapies and safety factors by the availability of new treatments. "In June 2006, the FDA approved ranibizumab for use in ARMD, but intravitreous injec- tions of bevacizumab, an anti-VEGF agent approved for systemic use in some cancers, was also being used off-label," Dr. Curtis said. "The rela- tive safety of the two therapies is un- known, although concerns had been raised about the safety of beva- cizumab when used in chemother- apy regimens." Included in the retrospective study were Medicare beneficiaries with ARMD claims. "We included Medicare fee-for-service beneficiaries with a diagnosis of ARMD from Jan- uary 1, 2005 to December 31, 2006, who received either PDT or intravit- reous injection of pegaptanib, beva- cizumab, or ranibizumab during that time period," Dr. Curtis said. "There were nearly 150,000 beneficiaries aged 65 and older in our analysis." Those included in the study were assigned to one of four groups. Patients who received PDT were put in the active control group. Those who received intravitreous medica- tion were grouped according to whether they were given pegaptanib octasodium, bevacizumab, or ranibizumab. Lower mortality risk One finding here was that mortality rates were significantly lower with ranibizumab therapy than with PDT or pegaptanib use. Likewise, there was less chance of myocardial infarc- tion for those treated with ranibizumab than with PDT. How- ever, Dr. Curtis attributes this to pa- tient-related factors rather than to the treatment given. "The fact that ranibizumab had lower risks than PDT, for which there is no evidence of adverse systemic effects, suggests that the individuals who received ranibizumab are healthier in ways that we couldn't measure," Dr. Cur- tis said. She theorizes that economic factors may be at play here. "There is a substantial cost difference between ranibizumab and bevacizumab and it's likely that higher income benefi- ciaries were more likely to receive ranibizumab," she said. "Higher in- come is often associated with better overall health." With this in mind, investigators performed a secondary analysis in which they limited the population to patients whose physicians pre- scribed bevacizumab or ranibizumab exclusively. This time the outcome was different. "We found that risks were not different between the groups," Dr. Curtis said. However, she acknowledged that the small sample size here leaves open the question of whether the results re- flect loss of statistical power or are reflective of what should have been the true outcome. Ultimately, investigators con- cluded that there was no increased risk for ARMD patients based upon the type of therapy selected. "The key finding was that bevacizumab and ranibizumab use wasn't associ- ated with increased risk of mortality, heart attack, bleeding, or stroke compared with PDT or pegaptanib," Dr. Curtis said. Clinical perspective From a clinical perspective Dr. Curtis sees the results as helping to sub- stantiate where things stand with the new medications. "The new data supports all three drugs' safety, but further analysis is needed to deter- mine if the drugs are safe for subsets of the macular degeneration popula- tion who have been identified as at high risk for cardiovascular events," Dr. Curtis said. Fellow investigator Scott W. Cousins, M.D., professor of ophthal- mology, Duke Eye Center, sees the study as bolstering confidence in the use of new medications for ARMD and helping to allay patients' fears. "Patients are always asking us about the side effects of the injection," he said. "Now I can tell them that these medications appear to be safe in the absence of high risk factors." He also sees this as important news for ophthalmologists who aren't in a position to observe the systemic impact associated with the drugs that they prescribe. "If the treatment creates a complication but you're not the doctor treating the complication, you may not notice that you're causing an adverse reac- tion," he said. "Therefore, as oph- thalmologists we may inadvertently miss some of these complications." In this study, however, he said that this fortunately did not appear to be the case for the majority of patients. Going forward, Dr. Curtis is al- ready planning to take another look at this for patients who are at high risk for complications. "We plan to examine the question again as addi- tive data accrue," she said. In partic- ular she hopes to assess relative risks in patients at high risk for cardiovas- cular events. EW Editors' note: The study was supported by a research agreement between Eyetech and Duke University. Contact information Cousins: scott.cousins@duke.edu Curtis: lesley.curtis@duke.edu January 2011 by Maxine Lipner Senior EyeWorld Contributing Editor Mortality, myocardial infarction, and more: Comparing risks of ARMD therapies The view of a patient with ARMD. Medications for ARMD pose no greater risk of mortality or cardiovascular events than PDT Source: National Eye Institute

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