title: Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol.
abstract: OBJECTIVE
  To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat-and-extend protocol for the treatment of neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters.
  
  
  METHODS
  Patients aged ≥ 50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity (BCVA) between 20/25 and 20/320.
  
  
  METHODS
  Patients were randomly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections. Monthly injections were given until inactive disease was achieved. The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks. If signs of recurrent disease appeared, the treatment interval was shortened by 2 weeks at a time.
  
  
  METHODS
  Change in visual acuity at 1 year.
  
  
  RESULTS
  Between March 2009 and July 2012, 441 patients were randomized at 10 ophthalmological centers in Norway. The 1-year visit was completed by 371 patients. In the per protocol analysis at 1 year, bevacizumab was equivalent to ranibizumab, with 7.9 and 8.2 mean letters gained, respectively (95% confidence interval [CI] of mean difference, -2.4 to 2.9; P = 0.845). The intention-to-treat analysis was concordant. There was no significant difference in measured central retinal thickness (CRT), with a mean decrease of -112 μm for bevacizumab and -120 μm for ranibizumab (95% CI of mean difference, -13 to 28; P = 0.460). There was a statistically significant difference (P = 0.001) between the drugs regarding the number of treatments: 8.9 for bevacizumab and 8.0 for ranibizumab. There were fewer arteriothrombotic events in the bevacizumab group (1.4%) than in the ranibizumab group (4.5%) (P = 0.050) and significantly more cardiac events in the ranibizumab group (P = 0.036). However, patients treated with ranibizumab more often had a history of myocardial infarction (P = 0.021).
  
  
  CONCLUSIONS
  Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat-and-extend protocol. The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment. The numbers of serious adverse events were small.
authors.affiliation: Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Karina
authors.initials: K
authors.lastname: Berg
authors.affiliation: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
authors.affiliation: Department of Statistics, Epidemiology and Health Economy, Oslo University Hospital, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.affiliation: Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: ragnheib@medisin.uio.no.
authors.forename: Ragnheiður
authors.initials: R
authors.lastname: Bragadóttir
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; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; 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