title: The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in nAMD: Systematic Review and Network Meta-Analysis.
abstract: Neovascular age-related macular degeneration (nAMD) is a chronic eye condition that causes severe deterioration of vision and ultimately blindness. Two vascular endothelial growth factor inhibitors are approved for nAMD treatment in Europe: ranibizumab and aflibercept. The European license for ranibizumab was updated with an individualized "treat and extend" (T&E) regimen, which involves more proactive treatment based on changes in best corrected visual acuity (BCVA) and/or anatomical outcomes. The aim of this publication is to compare the efficacy of the ranibizumab T&E regimen with other approved dosing regimens for nAMD on the basis of outcomes identified from a systematic review and subsequent NMA.
  
  
  
  Following a systematic search of publications, to identify relevant studies, a repeated-measures network meta-analysis (NMA) was performed to estimate the relative effectiveness of ranibizumab T&E versus approved dosing regimens of ranibizumab and aflibercept. The analysis focused on licensed treatment regimens for nAMD. We examined mean change from baseline in BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.
  
  
  
  The systematic literature review identified 22,949 records, of which 23 studies were included in the NMA. At 12 months, the ranibizumab T&E dosing regimen vs ranibizumab pro re nata (PRN) was associated with small differences in change in BCVA, between 1.86 letter gain at 12 months and 2.35 letter gain at 24 months. A similar difference was observed in the aflibercept dosing regimen versus ranibizumab T&E ; 1.94 letter gain at 12 months and 3.31 letter gain at 24 months. All doses of ranibizumab and aflibercept showed similar effectiveness, and the differences between treatment options were not significant.
  
  
  
  This study used novel repeated-measures NMA to synthesize efficacy results when treatment effects were reported at multiple follow-up times. This repeated-measures NMA suggests that treating patients with the ranibizumab T&E regimen yields similar effectiveness compared to other approved ranibizumab and aflibercept dosing regimens for nAMD treatment.
  
  
  
  Novartis Pharmaceuticals UK Ltd, Surrey, UK.
authors.affiliation: Novartis Ireland Limited, Dublin, Ireland. andrii.danyliv@novartis.com.
authors.forename: Andriy
authors.identifier: 0000-0002-1542-6499
authors.initials: A
authors.lastname: Danyliv
authors.affiliation: York Health Economics Consortium, University of York, York, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Glanville
authors.affiliation: York Health Economics Consortium, University of York, York, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: McCool
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferreira
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Skelly
authors.affiliation: Novartis Pharmaceuticals UK Limited, Surrey, UK.
authors.forename: Ruth Pulikottil
authors.initials: RP
authors.lastname: Jacob
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods; D005060:Europe; D006801:Humans; D000069579:Ranibizumab / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000187:drug effects; D057135:Wet Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Aflibercept; Neovascular age-related macular degeneration; Network meta-analysis; Ophthalmology; Ranibizumab; Systematic review; Treat and extend; Vascular endothelial growth factor inhibitors