Damian McNamara

May 09, 2013

SEATTLE, Washington — In patients with neovascular age-related macular degeneration, bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech) improve visual acuity to the same extent, according to 1-year results from a randomized trial.

"We're not saying bevacizumab is better; it's noninferior," said Laurent Kodjikian, MD, from Hopitaux de Lyon, in France. He presented the highly anticipated results to a packed room here at the Association for Research in Vision and Ophthalmology 2013 Annual Meeting.

The primary outcome of the prospective, double-blind, multicenter study, known as GEFAL (Groupe d'Evaluation Français Avastin vs Lucentis), was change in best-corrected visual acuity score between baseline and follow-up at least 10 months later.

A mean change in visual acuity of +1.89 letters favored bevacizumab, but both improvements fell within the 95% confidence interval range (–1.16 to +4.93), Dr. Kodjikian reported.

"There is no clinical relevance to a 1 or 2 letter difference." A prespecified difference of at least 5 letters was required to demonstrate superior visual acuity, he told Medscape Medical News.

The GEFAL study was conducted at 38 public and private clinic sites across France from June 2009 to November 2011.

Investigators randomized participants (mean age, 80 years) to 1 of the 2 vascular endothelial growth-factor inhibitors. A total of 191 patients received 1.25 mg bevacizumab and 183 received 0.5 mg ranibizumab intravitreal injections. A 3-month loading-dose period with monthly injections was followed by as-needed injections over the subsequent 9 months.

Table. One-Year GEFAL Outcomes

Outcome Bevacizumab Ranibizumab
Mean injections over 12 months (n) 6.8 6.5
Mean change visual acuity (letters) 5.36 3.63
Gain of 15 letters or more 20.4% 21.3%
Final visual acuity of 20/40 or better 41.4% 37.3%

 

There were no statistical differences in secondary anatomic outcomes between the bevacizumab and ranibizumab groups, including absence of intraretinal or subretinal fluid on optical coherence tomography (50.5% vs 58.2%; P = .1354), displayed presence of dye leakage on an angiogram (49.4% vs 41.3%; P = .1367), and mean change in subfoveal choroidal neovascularization from baseline (–0.27 vs –0.27).

In addition, changes in central subfield macular thickness at 12 months were similar in the bevacizumab and ranibizumab groups (–97.8 vs –109.9 µm).

There was no significant difference in adverse events, including death, serious infection, and serious gastrointestinal effects. "Although it's important to note that GEFAL was never powered for adverse events...we found no difference," Dr. Kodjikian said.

In addition to the GEFAL trial, Dr. Kodjikian and colleagues conducted a meta-analysis that combined findings from the Comparison of Age-related Macular Degeneration Treatment Trial (CATT) (Ophthalmology. 2012;119:1388-1398) and the IVAN trial (Ophthalmology. 2012;119:1399-411). "We found the same results — noninferiority of bevacizumab to ranibizumab for visual acuity at 1 year."

Unlike in the GEFAL trial, however, in the meta-analysis, bevacizumab was associated with more systemic serious adverse events than ranibizumab (odds ratio,1.24; 95% confidence interval, 0.70 - 2.20).

"But we have to be careful before drawing any conclusions," Dr. Kodjikian said. "When we looked at specific events, there were no statistical differences." Future study is warranted to evaluate each adverse event separately, relative to each drug, he added.

After the presentation, Paul Mitchell, MD, from the University of Sydney in Australia, asked about the 20% dropout rate in GEFAL.

Dr. Laure Huot, one of the GEFAL researchers, said that there was no significant difference in the rate of discontinuation between the groups.

Dr. Kodjikian explained that although the dropout rate is a potential limitation, it was anticipated and factored into the number of patients recruited for the study. He noted that the strengths of the study were its independence from industry funding, the double-blinding of vial contents for patients and ophthalmologists, and the real-life population treated at both public and private sites.

In the United States, ranibizumab is approved by the US Food and Drug Administration to treat wet age-related macular degeneration, but treatment with bevacizumab is considered off label.

This study was funded by the French Ministry of Health and the French Health Insurance System. Dr. Kodjikian reports receiving fees and being an advisory board member for Novartis, the manufacturer of ranibizumab in Europe. Dr. Mitchell reports that he is a researcher for Novartis.

Association for Research in Vision and Ophthalmology (ARVO) 2013 Annual Meeting. Presented May 7, 2013.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....