title: Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.
abstract: To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen.
  
  
  
  Randomized clinical trial.
  
  
  
  Six hundred sixty participants with visual acuity (VA) impairment from DME.
  
  
  
  Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable.
  
  
  
  Change in VA, adverse events, and retreatment frequency.
  
  
  
  Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders).
  
  
  
  All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.
authors.affiliation: Palmetto Retina Center, Columbia, South Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Wells
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Glassman
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida. Electronic address: drcrstat1@jaeb.org.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Ayala
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressler
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Brucker
authors.affiliation: National Eye Institutes, National Institutes of Health, Bethesda, Maryland.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Retina-Vitreous Surgeons of Central New York, PC, Syracuse, New York.
authors.forename: G Robert
authors.initials: GR
authors.lastname: Hampton
authors.affiliation: Retina Research Center, Austin, Texas.
authors.forename: Chirag
authors.initials: C
authors.lastname: Jhaveri
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Michele
authors.initials: M
authors.lastname: Melia
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; 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