Fran Lowry

June 07, 2012

June 7, 2012 (Fort Lauderdale, Florida) — Ranibizumab (Lucentis) and bevacizumab (Avastin) "confer equivalent visual function benefits," according to 1-year results from the Alternative Treatments to Inhibit VEGF in Age-Related Choroidal Neovascularization (IVAN) trial.

The drugs were equally effective clinically in this interim analysis (IVAN is due to run for 2 years); however, bevacizumab is a great deal less expensive, the IVAN researchers explained here at the Association for Research in Vision and Ophthalmology 2012 Annual Meeting.

Interim results from the IVAN trial were published online May 11 in Ophthalmology.

At the end of the first year, the IVAN trial showed that ranibizumab and bevacizumab have similar effectiveness. "Regardless of the drug received, or whether treatment was monthly or as needed, sight in the affected eye improved by 1 to 2 lines on a standard eye test," lead investigator Usha Chakravarthy, PhD, from Queen's University, Belfast, United Kingdom, told Medscape Medical News.

The IVAN trial is one of the largest ever conducted in the field of eye disease in the United Kingdom, and the results mirror those of the Comparison of AMD Treatments Trials (CATT) study conducted in the United States.

The IVAN trial is a multicenter noninferiority study that sought to compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections in the treatment of neovascular age-related macular degeneration (AMD).

The study involved 610 patients 50 years or older with previously untreated neovascular AMD in the study eye who were randomized, from March 2008 to October 2010, to receive ranibizumab or bevacizumab given either every month (continuous) or as needed (discontinuous), with monthly review.

Results Confirm Noninferiority

A year after randomization, the comparison of bevacizumab and ranibizumab was inconclusive, Dr. Chakravarthy said.

Mean acuities were 69.0 letters in the ranibizumab group and 66.1 letters in the bevacizumab group, and 66.8 letters with the continuous regimen and 68.4 letters with the discontinuous regimen. The difference between bevacizumab and ranibizumab was 1.99 letters (95% confidence interval [CI], –4.04 to 0.06). The difference between the discontinuous and continuous treatment regimens was 0.35 (95% CI, –2.40 to 1.70).

The interim results show that foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P =.005).

Dr. Chakravarthy reported that there were fewer arteriothrombotic events and heart failures with bevacizumab than with ranibizumab (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P =.03). "This was not observed in CATT," she noted.

Additionally, the proportion of patients experiencing a serious systemic adverse event was similar in the 2 groups (OR, 1.35; 95% CI, 0.80 to 2.27; P =.25).

Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P < .0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P =.004).

The National Health Service Could Save Millions

Although there was no functional difference between the 2 drugs, bevacizumab is considerably less expensive.

"The National Health Service could save £84.5 million a year, based on treating 17,295 eyes each year, by switching from [ranibizumab] to [bevacizumab] and administering the treatment on an as-needed basis," said coauthor Simon P. Harding, MD, from the University of Liverpool in the United Kingdom.

Currently, ranibizumab is the only agent licensed in the United Kingdom to treat neovascular AMD. Given the interim results of the IVAN trial and the 2-year results of the CATT study, Medscape Medical News asked Dr. Harding if there is a future for the considerably more costly ranibizumab.

"We have a decision to make about what happens next; until the IVAN trial produced its 12-month results, decision-makers were deferring the decision on whether to recommend the switch from [ranibizumab] to [bevacizumab]," he said.

In the United Kingdom, ranibizumab is licensed for wet AMD but bevacizumab is not. "A judgment has to be made as to whether we think that the saving in switching to [bevacizumab] is worth breaking the long-established dictum in the United Kingdom that you should only use a licensed drug when it is available. That debate is now going to start," he said.

Commenting on the IVAN trial for Medscape Medical News, Daniel F. Martin, MD, from the Cole Eye Institute, Cleveland Clinic in Ohio, who led the CATT study, said that given the results, he will begin treating patients with bevacizumab on an as-needed basis.

"There is a subset of patients who do not need monthly treatment, and there are some who only need 1, 2, or 3 injections in the course of a year. If a patient wants the more expensive ranibizumab, of course I'll give them what they want, but if it is up to me, I'll start with [bevacizumab]."

The IVAN trial was sponsored by Belfast Health and Social Care Trust. Dr. Chakravarthy reports financial relationships with Novartis, Allergan, Bausch & Lomb, and Bayer. Dr. Martin has disclosed no relevant financial relationships.

Ophthalmology. Published online May 11, 2012. Abstract

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


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