PHILADELPHIA - Two drugs commonly used to treat age-related macular degeneration (AMD) yield similar improvements in vision for patients receiving treatments on a monthly or as-needed basis, according to a study from researchers at the Center for Preventive Ophthalmology and Biostatistics (CPOB) at the Perelman School of Medicine at the University of Pennsylvania. The year-two results of the Comparison of AMD Treatment Trials (CATT) support the findings from the first year of the study that evaluated the effects of Avastin ® (bevacizumab) - the off-label drug most frequently used to treat AMD - and Lucentis® (ranibizumab), a drug approved by the FDA in 2006 for the treatment of AMD. Full long-term results of the CATT, a two-year clinical trial, are published in the current issue of Ophthalmology.
"Regardless of which drug is used, treating AMD requires repeated treatment to prevent loss of vision. These year-two results show that long-term treatment with either Avastin or Lucentis results in similar levels of improvement for these patients suffering from AMD," said Maureen Maguire, PhD, corresponding author on the study and director, CPOB. "We knew these options were available and the drugs were effective in the short-term, but what's become more clear is that the differences between the two drugs over a longer period of time are still almost non-existent - the impact on vision is virtually the same, no matter which drug is used."
Improvement in visual clarity served as the primary outcome measure for the year-two results. AMD is the leading cause of vision loss and blindness in older Americans. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula - the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail - and obscure vision. Accumulation of fluid and blood damages the macula causing loss of central vision. Without treatment, most patients with AMD are unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.
Avastin - a drug approved for the treatment of some cancers but not AMD - and Lucentis block growth of abnormal blood vessels and leakage of fluid from the vessels. CATT was originally designed to compare the effectiveness of Avastin and Lucentis as a treatment for AMD. However, in the initial studies for AMD, Lucentis was administered monthly. For the year-two study, researchers focused on determining whether "as-needed" dosing would produce the same long-term visual improvements.
At enrollment, patients were assigned to one of four treatment groups defined by drug (Avastin or Lucentis) and dosing regimen (monthly or as-needed). Patients in the monthly dosing groups received a treatment injection every 28 days. Patients in the as-needed groups received a treatment at baseline and were then examined every 28 days to determine medical need for additional treatment. The original CATT study followed 1185 patients treated at 43 clinical centers in the United States. During year two, researchers examined the continued effects seen in 1107 patients.
"At two years, both drugs proved highly effective regardless of the dosing regimen. Clarity of vision in the patients who received monthly treatments was only slightly better than in those who received treatment as-needed, but all four groups exhibited significant improvement," said Juan Grunwald, MD, professor of Ophthalmology and Principal Investigator of the Photography Reading Center. "Additionally, the lasting improvement these patients experienced is remarkable. After two years, two-thirds of patients had driving vision (20/40 vision or better). In previous studies, only 15 percent of patients retained similar visual acuity.
When tested on a standard eye chart, patients who received monthly treatments experienced an average improvement of about half a line better than those in the as-needed group. Changes in retinal anatomy differed by drug and frequency of treatment, but did not have an impact on vision through 2 years. Though results showed slightly less vision gain with as-needed treatment, researchers say benefits and drawbacks to both regimens should be considered by patients and clinicians.
"Patients who want the small extra advantage afforded with the monthly treatment should also be aware of the additional risks and costs of the monthly injections," explains Maguire. "Those in the as-needed group ultimately required 10 fewer injections over the course of two years and experienced similar visual improvements."
Adverse events indicate development or worsening of a medical condition. They may or may not be causally associated with the clinical trial treatment, but they are always monitored and reported in any clinical trial. The median age of patients in CATT was over 80 years, and a high rate of hospitalizations would be anticipated as a result of chronic or acute medical conditions more common to older populations.
Serious adverse events (SAEs) occurred at a 40 percent rate for patients receiving Avastin and a 32 percent rate for patients receiving Lucentis. Although Avastin had a higher rate of SAEs, they were distributed across many different conditions, most of which were not associated with Avastin when evaluated in cancer clinical trials where the drug was administered at 500 times the dose used for AMD. The number of deaths, heart attacks, and strokes were low and similar for both drugs during the study. Additional data from other clinical trials comparing Avastin and Lucentis may provide further information on the long-term safety profiles of these drugs when used to treat AMD.
This study was funded by the National Eye Institute, a part of the National Institutes of Health (5U10EY017828-08). First year results were published in the May 19th, 2011 issue of the New England Journal of Medicine.
Lucentis® and Avastin® are products of Genentech, Inc.
Drs. Maguire and Grunwald have no relevant disclosures.
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