title: Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study.
abstract: OBJECTIVE
  To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME).
  
  
  METHODS
  Twenty-four-month, open-label, multicenter, Phase IIIb extension study.
  
  
  METHODS
  Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension.
  
  
  METHODS
  All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension.
  
  
  METHODS
  Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA.
  
  
  RESULTS
  Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 μm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 μm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 μm, and 4.3, respectively), with an average of 4.1 ranibizumab injections.
  
  
  CONCLUSIONS
  Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Division of Medical Retina and Laser Surgery, Department of Ophthalmology, University of Ulm, Ulm, Germany. Electronic address: gabriele.lang@uniklinik-ulm.de.
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Lang
authors.forename: András
authors.initials: A
authors.lastname: Berta
authors.forename: Bora M
authors.initials: BM
authors.lastname: Eldem
authors.forename: Christian
authors.initials: C
authors.lastname: Simader
authors.forename: Dianne
authors.initials: D
authors.lastname: Sharp
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.forename: Florian
authors.initials: F
authors.lastname: Sutter
authors.forename: Ortrud
authors.initials: O
authors.lastname: Gerstner
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy*; D008297:Male; D000069579:Ranibizumab; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab