title: Ranibizumab vs. aflibercept for wet age-related macular degeneration: network meta-analysis to understand the value of reduced frequency dosing.
abstract: OBJECTIVE
  Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare the efficacy and safety of reduced frequency dosing for aflibercept, relative to other approved and marketed vascular endothelial growth factor inhibitors for wet AMD, over 12 months.
  
  
  METHODS
  Based on a systematic literature review performed according to a pre-specified protocol, a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5 mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard NMA models were used to analyze change at 3 months, and fractional polynomial regression over 12 months. Safety data were analyzed using binomial models with a logistic link function.
  
  
  RESULTS
  Five trials formed a complete evidence network. At 3 months, all posologies of aflibercept and ranibizumab resulted in similar changes in BCVA. Over 12 months, approved posologies of aflibercept and ranibizumab resulted in similar changes from baseline, between 6.7 (95% credible interval [CrI], 5.5, 7.8) and 9.1 (8.1, 10.1) ETDRS letters; however, reduced frequency aflibercept was associated with a smaller change (1.8 letters, [-25.9, 29.2]). There was a trend towards a greater change in BCVA, with increasing frequency of dosing. All posologies performed similarly with respect to safety, and CrIs were wide.
  
  
  CONCLUSIONS
  Approved posologies of ranibizumab and aflibercept are similarly effective treatments for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.
authors: a a Redwood Outcomes , Vancouver , Canada.
authors: Shelagh M
authors: SM
authors: Szabo
authors: b b Novartis Healthcare , Copenhagen , Denmark.
authors: Morten
authors: M
authors: Hedegaard
authors: a a Redwood Outcomes , Vancouver , Canada.
authors: Keith
authors: K
authors: Chan
authors: a a Redwood Outcomes , Vancouver , Canada.
authors: Kristian
authors: K
authors: Thorlund
authors: c c The Parker Institute, Department of Rheumatology, Copenhagen University Hospital , Copenhagen , Denmark.
authors: Robin
authors: R
authors: Christensen
authors: d d Department of Ophthalmology , Aalborg University Hospital , Aalborg , Denmark.
authors: Henrik
authors: H
authors: Vorum
authors: e e Redwood Outcomes , San Francisco , USA.
authors: Jeroen P
authors: JP
authors: Jansen
mesh_terms: D001499:Bayes Theorem; D006801:Humans; D000069579:Ranibizumab / Q000008:administration & dosage*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy*
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Age-related macular degeneration; Network meta-analysis; Systematic review; Vascular endothelial growth factor inhibitors