Fran Lowry

May 08, 2012

May 8, 2012 (Fort Lauderdale, Florida) — Bevacizumab (Avastin, Genentech) is just as effective as ranibizumab (Lucentis, Genentech) for the treatment of neovascular age-related macular degeneration (AMD) when using similar dosing regimens, researchers reported here at the Association for Research in Vision and Ophthalmology (ARVO) 2012 Annual Meeting.

The results of the second year of the Comparison of Age-related macular degeneration Treatment Trials (CATT) were presented by Daniel F. Martin, MD, of the Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Full results were also published in the May issue of Ophthalmology.

Bevacizumab is not only just as effective but also far less costly. This fact will make it the drug of choice for many clinicians and their patients, Dr. Martin said.

"I would choose Avastin because it is so much cheaper and we are in times where every penny, every pound, counts. There would be no question," Usha Chakravarthy, MD, from Queens University, Belfast, Ireland, told reporters at a press conference.

Dr. Chakravarthy was not part of CATT. However, she headed a similar trial in the United Kingdom, the IVAN trial, that also found equal efficacy of the 2 drugs at 12 months.

Clinical trials established that ranibizumab was highly effective treatment for neovascular, or wet, AMD. It was specifically designed to treat AMD and received approval by the US Food and Drug Administration (FDA) in 2006.

While waiting for the FDA to approve ranibizumab, ophthalmologists began using bevacizumab off-label because its method of action was similar to that of ranibizumab. In addition, it was available at relatively low cost, Dr. Martin said.

Bevacizumab consequently became the most commonly used drug for the treatment of neovascular AMD, but there were no data from randomized clinical trials to support its use.

Accordingly, the CATT researchers set out to compare the efficacy of the 2 agents.

The 1-year results of the comparison, which were reported in May 2011, showed that both drugs had nearly identical effects on visual acuity and that less than monthly, or as-needed, dosing regimens did not adversely affect vision.

The 1-year results also showed that both drugs reduced retinal and subretinal fluid but that ranibizumab eliminated fluid more often.

However, although rates of death and atherothrombotic events did not differ between the drugs, bevacizumab was associated with more serious adverse events, including gastrointestinal disorders and endophthalmitis.

Patients Randomly Assigned to 4 Different Treatment Regimens

CATT investigators assigned 1185 patients to 1 of 4 treatment groups: ranibizumab monthly (every 4 weeks) or as needed, or bevacizumab monthly or as needed (patients were evaluated every 4 weeks and treated when fluid was present on optical coherence tomography [OCT] or when new or persistent hemorrhage, decreased visual acuity relative to the previous visit, or dye leakage on fluorescein angiography was present.

At the end of the first year, patients who were assigned to monthly treatment were randomly assigned to continue monthly treatment or switch to as-needed treatment. Patients initially assigned to as-needed treatment continued that regimen.

The dose per intravitreal injection was 0.50 mg ranibizumab in 0.05-mL solution or 1.25 mg bevacizumab in 0.05-mL solution.

At 2 years, the mean gain in visual acuity was similar for both ranibizumab and bevacizumab in the 1030 patients who had visual acuity scores available for analysis.

The difference in mean improvement for patients treated with bevacizumab relative to those treated with ranibizumab was a nonsignificant -1.4 letters (95% confidence interval [CI], -3.7 to 0.8 letters; P = .21).

The mean gain was greater for patients treated monthly than for those treated as needed (difference, -2.4 letters; 95% CI, -4.8 to -0.1 letters; P = .046).

The proportions of patients without a decrease in vision of 15 letters or more were similar and ranged from 88.4% of those treated with bevacizumab as needed to 93.3% of those treated with ranibizumab monthly.

Additionally, the proportion of patients without fluid ranged from 13.9% in the bevacizumab-as-needed patients to 45.5% in the ranibizumab-monthly patients (P = .0003 for drug; P = .0001 for regimen).

The study also found that switching from monthly to as-needed treatment resulted in a greater mean decrease in vision during year 2 (-2.2 letters; P = .03) and a lower proportion of patients without fluid (-19%; P < .0001).

As in the first-year results, rates of death and atherothrombotic events were similar for both drugs (P > .60). However, bevacizumab continued to be associated with higher rates of systemic serious adverse events. The proportion of patients with 1 or more systemic serious adverse events was 39.9%, compared with 31.7% for patients treated with ranibizumab (adjusted risk ratio, 1.30; 95% CI, 1.07 - 1.57; P = .009).

CATT Investigators Puzzled About Serious Adverse Events With Bevacizumab

"It's a shame that we have to use the words 'serious adverse events' because a lot of reasons why people go to the hospital, at least in the US, are not serious. If you show up in the emergency room with dehydration, or a hernia, or a urinary tract infection, that will be reported as an SAE," Dr. Martin told Medscape Medical News.

"We exhaustively looked at this and at the end of the day, we had to say we don't know the reason. But there is a concern. However, the majority of SAEs have never been described as being VEGF [vascular endothelial growth factor]-related, and that's important," he said.

In addition, the patients in the bevacizumab group were sicker at baseline, Dr. Martin said.

"The Avastin patients were a year older, had more hypertension, diabetes, history of stroke, more congestive heart failure, more Plavix and Coumadin use, so when you look numerically you get the impression that this group might have been sicker. You have to be careful not to become biased when you look at these numbers, but there are imbalances at baseline, and it is possible that this might account for the increased SAEs, but it also may be possible that it does not."

With these results, Dr. Martin said he would leave the choice of drug up to the patient, but his preference would be to start with bevacizumab as needed and see how the patient responds.

"If there is a problem you can then move on to the more expensive drug," he said.

Dr. Chakravarthy told Medscape Medical News that patients who have gastrointestinal problems might be "safer" with ranibizumab, but that is difficult to say with certainty. "In terms of safety one could envisage a scenario where such patients might be safer, but we don't have that information yet with patient subtypes."

The study was funded by the National Eye Institute, National Institutes of Health, Department of Health and Human Services. Dr. Martin and Dr. Chakravarthy have disclosed no relevant financial relationships.

The Association for Research in Vision and Ophthalmology (ARVO) 12th Annual Meeting. Presented May 6, 2012.


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