title: Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study.
abstract: OBJECTIVE
  Because many patients with diabetic macular edema (DME) do not respond to focal/grid laser photocoagulation, the only currently approved treatment, alternatives are needed. Based on encouraging preliminary findings, we aimed to assess efficacy and safety of the anti-tumor necrosis factor (TNF) monoclonal antibody infliximab in this condition.
  
  
  METHODS
  This was a single-center, double-blind, randomized, placebo-controlled, crossover study. Eleven patients with sight-threatening DME persisting after two sessions of laser photocoagulation received infliximab (5 mg/kg) intravenously at weeks 0, 2, 6, and 14, followed by placebo at weeks 16, 18, 22, and 30, or vice versa. Blinding was maintained to week 32, when the final assessments were performed. Best corrected visual acuity evaluated by a mixed-models approach for imbalanced crossover design using the percentage difference as the outcome variable was the primary study end point. Data were analyzed on an intention-to-treat basis.
  
  
  RESULTS
  Early Treatment of Diabetic Retinopathy Study (ETDRS) scores dropped from 31.6 +/- 5.1 (mean +/- SD) letters read at baseline to 28.8 +/- 11.6 letters read at week 16 in six placebo-treated eyes and improved to 35.4 +/- 11.2 letters read after infliximab. In contrast, visual acuity improved from 23.5 +/- 10.3 at baseline to 30.4 +/- 13.4 letters read at week 16 in eight infliximab-treated eyes and was sustained at completion of placebo treatment (31.4 +/- 12.1 letters read). The excess visual acuity in infliximab-treated eyes was greater by 24.3% compared with that in placebo-treated eyes (95% CI 4.8-43.7; P = 0.017). Infliximab treatment was well tolerated.
  
  
  CONCLUSIONS
  The positive results of this small phase III study suggest that larger and longer term trials should be conducted to assess the efficacy of systemic or intravitreal anti-TNF agent administration for primary treatment of DME.
authors.affiliation: First Department of Propaedeutic and Internal Medicine, Laiko General Hospital, Athens, Greece. psfikakis@med.uoa.gr
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
authors.forename: Vlassis
authors.initials: V
authors.lastname: Grigoropoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Emfietzoglou
authors.forename: George
authors.initials: G
authors.lastname: Theodossiadis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tentolouris
authors.forename: Evi
authors.initials: E
authors.lastname: Delicha
authors.forename: Christina
authors.initials: C
authors.lastname: Katsiari
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Alexiadou
authors.forename: Erifili
authors.initials: E
authors.lastname: Hatziagelaki
authors.forename: Panayiotis G
authors.initials: PG
authors.lastname: Theodossiadis
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069285:Infliximab; D017075:Laser Coagulation; D008269:Macular Edema / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab