Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis

BMJ Open. 2019 May 28;9(5):e022031. doi: 10.1136/bmjopen-2018-022031.

Abstract

Objectives: To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).

Design: Systematic review and random-effects meta-analysis.

Methods: Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.

Results: 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6-9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.

Conclusions: Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.

Prospero registration number: CRD42015022041.

Keywords: aflibercept; age-related macular degeneration; anti-vascular endothelial growth factor; bevacizumab; diabetic macular edema; myopic choroidal neovascularization; ranibizumab; retinal vein occlusion.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use*
  • Choroidal Neovascularization / drug therapy
  • Diabetic Retinopathy / drug therapy
  • Humans
  • Macular Degeneration / drug therapy
  • Macular Edema / drug therapy
  • Ranibizumab / administration & dosage
  • Ranibizumab / adverse effects
  • Ranibizumab / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Retinal Diseases / drug therapy*
  • Retinal Vein Occlusion / drug therapy
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab

Grants and funding