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Bevacizumab, Ranibizumab Equally Improve Age-Related Macular Degeneration

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Study Supports Common Clinical Practice

The researchers have provided the evidence of equal efficacy between bevacizumab and ranibizumab that had been lacking, Dr. Philip J. Rosenfeld wrote in an accompanying editorial (N. Engl. J. Med. 2011 April 28 [doi: 10.1056/NEJMe1103334]).

In addition, the findings support the validity of an as-needed treatment regimen with either drug. "Critics will argue that the OCT [optical coherence tomography] outcomes suggest differences between these two drugs," he said. "Although the OCT retinal thickness measurements favor ranibizumab, this difference is not reflected in any of the visual-acuity or angiographic outcomes," said Dr. Rosenfeld. "Whether this difference is associated with changes in vision should become clear during the second year of follow-up," he added.

Dr. Philip J. Rosenfeld is an ophthalmologist at Bascom Palmer Eye Institute in Miami. He has served as a consultant for Oraya, Novartis, Chengdu Kanghong Biotech, and GlaxoSmithKline. He has received grants or speaker’s payments from Carl Zeiss, Alexion Pharmaceuticals, Potentia, Comentis, Allergan, and Topcon.


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Age-related macular degeneration improved equally in patients treated with monthly bevacizumab or monthly ranibizumab, and as-needed dosing was almost as effective as monthly injections, according to data from 1-year results of a 2-year clinical trial. The findings were published online April 28 in the New England Journal of Medicine.

After 1 year of treatment, the two drugs were "equivalent for visual acuity at all time points when administered at the same dosing regimen," Dr. Daniel Martin of the Cleveland Clinic said in a teleconference.

Bevacizumab (Avastin) has been used off label for age-related macular degeneration (AMD), but formal efficacy data were lacking, said Dr. Paul Sieving, director of the National Eye Institute, which sponsored the study.

In addition, "both drugs produced an immediate and substantial decrease in the amount of fluid in the retina," Dr. Martin said.

As-needed dosing resulted in a lower treatment burden for patients, with "an average of 4 to 5 fewer injections over 1 year than patients assigned to monthly dosing," Dr. Martin noted. As-needed dosing yielded slightly less improvement, but "the results were still excellent," he said (N. Engl. J. Med. 2011 April 28 [doi: 10.1056/NEJM0a1102673]).

In the Comparison of AMD Treatments Trial (CATT), Dr. Martin and the CATT Research Group enrolled 1,208 adults aged 50 years or older with AMD at 44 clinical sites between February 2008 and December 2009. Patients were randomized into four groups: monthly ranibizumab, monthly bevacizumab, ranibizumab as needed, and bevacizumab as needed.

The ranibizumab dose was 0.50 mg in 0.05 mL of solution, and the bevacizumab dose was 1.25 mg in 0.50 mL of solution.

After 23 patients at one center were eliminated because of protocol noncompliance, 1-year results were available for 1,185 patients.

After 1 year of treatment, visual acuity (defined as number of letters the patients could read on an eye chart) improved across all four groups. The changes in visual acuity scores from baseline in the ranibizumab monthly, bevacizumab monthly, ranibizumab as needed, and bevacizumab as needed groups were 8.5, 8.0, 6.8, and 5.9, respectively. Ranibizumab was statistically equivalent to bevacizumab both when the drugs were given monthly and when they were given as needed.

In all four groups, the greatest improvements occurred during the first 3 months of treatment, the researchers noted.

In a longitudinal analysis, the mean increases in number of letters, compared with baseline in the four groups were 7.2, 7.3, 6.4, and 6.1, respectively.

The baseline demographics were similar across all four groups. The average age ranged from 78 to 80 years, approximately two-thirds of patients in each group were women, and at least 98% of each group was white.

The incidence of serious systemic adverse events was 18% in the ranibizumab monthly group, 22% in the bevacizumab monthly group, 21% in the ranibizumab as-needed group, and 26% in the bevacizumab as-needed group. These differences were not significant.

The difference in the cost of the two medications remains a factor in drug choice, the researchers noted. "A single dose of ranibizumab costs 40 times as much as a single dose of bevacizumab," they wrote. The average cost of the medications per patient for 1 year was $23,400 in the ranibizumab monthly group, $13,800 in the ranibizumab as-needed group, $595 in the bevacizumab monthly group, and $385 in the bevacizumab as-needed group.

Currently, most AMD patients in the United States receive bevacizumab, and the study "provides data to support what is the dominant practice pattern in the United States," said Dr. Martin. Both drugs could be considered standard of care, and both are viable options, he said. "Clinicians may choose one or the other, and this study has informed that choice," he added.

The CATT study is ongoing, and additional results will be published at the end of 2 years.

The study was funded by a grant from the National Eye Institute. Dr. Martin had no additional financial conflicts to disclose.

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