title: Efficacy and adverse events of aflibercept, ranibizumab and bevacizumab in age-related macular degeneration: a trade-off analysis.
abstract: OBJECTIVE
  To quantify the gain in visual acuity and serious side effects of ranibizumab, bevacizumab and aflibercept in age-related macular degeneration (AMD).
  
  
  CONCLUSIONS
  There is an ongoing debate about the optimal treatment of AMD with these three antivascular endothelial growth factor (anti-VEGF) treatments.
  
  
  METHODS
  Network meta-analyses. (Pre)Medline, EMBASE, SCOPUS, Cochrane Library (until April 2013), Science Citation Index and reference lists were searched for placebo-controlled randomised trials or head-to-head comparisons. Outcomes were 1-year follow-up data of visual acuity (letters gained) and serious (vascular death, any death, stroke, myocardial infarction, transient ischaemic attack) and thrombotic events. Two investigators independently assessed eligibility and quality of included studies and extracted data.
  
  
  RESULTS
  11 trials (enrolling 8341 patients) assessing five active treatments were included. Compared with placebo, all anti-VEGF treatments had a significantly higher percentage of letters gained: ranibizumab 0.3 mg 2.39% (95% CI 1.59 to 3.19; p<0.001), ranibizumab 0.5 mg 3.56% (95% CI 2.58 to 4.13; p<0.001), bevacizumab 1.25 mg 2.14% (95% CI 0.47 to 3.82; p=0.012), aflibercept 0.5 mg 2.91% (95% CI 0.99 to 4.82; p=0.003) and aflibercept 2 mg 3.44% (95% CI 1.73 to 5.14; p<0.001). Compared with placebo, serious side effects were higher in all other treatments: ranibizumab 0.3 mg 4.41% (95% CI 3.42 to 5.40; p<0.001), ranibizumab 0.5 mg 5.33% (95% CI 4.37 to 6.30; p<0.001), bevacizumab 1.25 mg 5.58% (95% CI 3.567 to 7.60; p<0.001), aflibercept 0.5 mg 5.65% (95% CI (3.28 to 8.02; p<0.001) and aflibercept 2 mg 5.29% (95% CI 3.18 to 7.39; p<0.001). Compared with placebo, systemic thrombotic events also occurred more often in all other treatments.
  
  
  CONCLUSIONS
  The study revealed only a modest superiority of aflibercept 2 mg and ranibizumab 0.5 mg over other formulations and dosages.
authors.affiliation: Eye Clinic, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schmid
authors.affiliation: Medignition Inc. Research Consultants, Zug, Switzerland.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Bachmann
authors.affiliation: Medignition Inc. Research Consultants, Zug, Switzerland.
authors.forename: Livia
authors.initials: L
authors.lastname: Fäs
authors.affiliation: Department of Clinical Epidemiology and Medical, Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Alfons G
authors.initials: AG
authors.lastname: Kessels
authors.affiliation: Eye Clinic, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Job
authors.affiliation: Eye Clinic, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thiel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016208:Databases, Factual; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Macula; Treatment Medical