title: Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration.
  
  
  METHODS
  Twelve-month, phase III, multicenter, open-label, single-arm study.
  
  
  METHODS
  A total of 513 ranibizumab-naïve SUSTAIN patients.
  
  
  METHODS
  Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe.
  
  
  METHODS
  Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed.
  
  
  RESULTS
  A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity [VA], vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 μm from baseline to month 3 and -91.5 μm from baseline to month 12.
  
  
  CONCLUSIONS
  The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies; individualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with individualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period.
authors: Department of Ophthalmology, University of Bonn, Bonn, Germany. Frank.Holz@ukb.uni-bonn.de
authors: Frank G
authors: FG
authors: Holz
authors: Winfried
authors: W
authors: Amoaku
authors: Juan
authors: J
authors: Donate
authors: Robyn H
authors: RH
authors: Guymer
authors: Ulrich
authors: U
authors: Kellner
authors: Reinier O
authors: RO
authors: Schlingemann
authors: Andreas
authors: A
authors: Weichselberger
authors: Giovanni
authors: G
authors: Staurenghi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D012160:Retina / Q000473:pathology; D019233:Retreatment; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab