title: The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model.
abstract: OBJECTIVE
  Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression.
  
  
  METHODS
  For visual acuity (VA), a model was developed on the 12-month data from ANCHOR, MARINA, and PIER. Data from untreated patients were used to model patient-specific disease progression in terms of VA loss. Data from treated patients from the period after the three initial injections were used to model the effect of predicted ranibizumab vitreous concentration on VA loss. The model was checked by comparing simulations of VA outcomes after monthly and quarterly injections during this period with trial data. A flexible VA-guided regimen (after the three initial injections) in which treatment is initiated by loss of >5 letters from best previously observed VA scores was simulated.
  
  
  RESULTS
  Simulated monthly and quarterly VA-guided regimens showed good agreement with trial data. Simulation of VA-driven individualized treatment suggests that this regimen, on average, sustains the initial gains in VA seen in clinical trials at month 3. The model predicted that, on average, to maintain initial VA gains, an estimated 5.1 ranibizumab injections are needed during the 9 months after the three initial monthly injections, which amounts to a total of 8.1 injections during the first year.
  
  
  CONCLUSIONS
  A flexible, individualized VA-guided regimen after the three initial injections may sustain vision improvement with ranibizumab and could improve cost-effectiveness and convenience and reduce drug administration-associated risks.
authors: Department of Ophthalmology, University of Bonn, Bonn, Germany. frank.holz@ukb.uni-bonn.de
authors: Frank G
authors: FG
authors: Holz
authors: Jean-François
authors: JF
authors: Korobelnik
authors: Paolo
authors: P
authors: Lanzetta
authors: Paul
authors: P
authors: Mitchell
authors: Ursula
authors: U
authors: Schmidt-Erfurth
authors: Sebastian
authors: S
authors: Wolf
authors: Sabri
authors: S
authors: Markabi
authors: Heinz
authors: H
authors: Schmidli
authors: Andreas
authors: A
authors: Weichselberger
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D018450:Disease Progression; D005260:Female; D006801:Humans; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological; D016032:Randomized Controlled Trials as Topic; D000069579:Ranibizumab; D019233:Retreatment; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology*; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab