Elsevier

Ophthalmology

Volume 120, Issue 11, November 2013, Pages 2300-2309
Ophthalmology

Original article
Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial

The results of GEFAL study were presented at: the Association for Research and Ophthalmology meeting, May 7, 2013, Seattle, Washington, and the Société Française d'Ophtalmologie meeting, May 11, 2013, Paris, France.
https://doi.org/10.1016/j.ophtha.2013.06.020Get rights and content

Objective

To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD).

Design

Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters.

Participants

Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA).

Methods

Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up.

Main Outcome Measures

Mean change in visual acuity at 1 year.

Results

Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], −1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups.

Conclusions

Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Design

The GEFAL study is a prospective, noninferiority, double-masked, randomized clinical trial performed in public and private French ophthalmology centers.

Study Population

Patients aged >50 years were eligible if they met the following inclusion criteria for the study eye (1 eye per patient): (1) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) measured on Early Treatment of Diabetic Retinopathy Study (ETDRS) charts at a distance of 4 m; (2) active subfoveal neovascular AMD; and

Patients

Overall, 501 patients were enrolled in 38 French centers between June 24, 2009, and November 9, 2011. According to our population definition, 374 patients (75%) were available for the per protocol analysis (Fig 1): 191 treated with bevacizumab and 183 treated with ranibizumab.

The initial demographic, clinical, OCT, and angiographic characteristics were similar between the 2 groups except for history of hypertension (Table 1). Mean BCVA at baseline was 54.6 letters in the bevacizumab group and

Discussion

Bevacizumab was found to be noninferior to ranibizumab with a difference in mean change in BCVA (bevacizumab minus ranibizumab) of +1.89 letters (95% CI, −1.16 to +4.93), which was confirmed by the intention-to-treat analysis.

These findings point in the same direction as those of the CATT study, which demonstrated that bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year14 (and at 2 years15) whether administered monthly or as needed. The MANTA study also found similar

Acknowledgments

The authors thank Professor Michel Lièvre for methodological assistance.

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      Second, the follow-up of this study was only 12 months, which is relatively short in comparison with the natural history of the disease that develops over years. Third, most of the randomized controlled trials on neovascular AMD reported the number of patients who lost more than 15 letters during the follow-up period.3,4,9 However, we deliberately chose to use the threshold of a loss of 5 letters or more to include all the patients with a significant and clinical decrease in visual acuity from baseline.

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    Financial Disclosure(s): The author(s) have made the following disclosure(s): L.K. is the Principal Investigator for trials sponsored by Novartis, Bausch & Lomb, Théa, and Alcon; has sat on advisory boards for Alcon, Allergan, Bayer, Bausch & Lomb, Novartis, and Théa; and has received lecture fees from Alcon, Allergan, Bayer, Bausch & Lomb, the Krys group, Novartis, Théa, and Zeiss. E.H.S. has received honoraria from Novartis, Bayer, and Allergan; has sat on advisory boards for Bausch & Lomb and Théa; and has received lecture fees from Bausch & Lomb and consulting fees from Novartis, Bayer, and Allergan. G.M. has received lecture fees from Allergan and Novartis. M.M-F. has sat on advisory boards for Novartis and Bayer, and has received lecture fees from Théa and Heidelberg Engineering. F.B-C., E.D., L.H., and G.A. declared no conflicts of interest.

    Supported by a grant from the French Ministry of Health (“Programme Hospitalier de Recherche Clinique National 2008”). The French Health Insurance System co-financed the study and funded drugs. The funding organizations had no role in designing or carrying out this research.

    Group members listed in Appendix 1 (available at http://aaojournal.org).

    The GEFAL Study Group members are listed in Appendix 1 (available at http://aaojournal.org).

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