title: Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial.
abstract: 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).
  
  
  METHODS
  Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service d'ophtalmologie, Lyon, France; Université de Lyon, Lyon, France; CNRS UMR 5510 Mateis, Villeurbanne, France. Electronic address: laurent.kodjikian@chu-lyon.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjikian
authors.forename: Eric H
authors.initials: EH
authors.lastname: Souied
authors.forename: Gérard
authors.initials: G
authors.lastname: Mimoun
authors.forename: Martine
authors.initials: M
authors.lastname: Mauget-Faÿsse
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Evelyne
authors.initials: E
authors.lastname: Decullier
authors.forename: Laure
authors.initials: L
authors.lastname: Huot
authors.forename: Gilles
authors.initials: G
authors.lastname: Aulagner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069579:Ranibizumab; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab