Efficacy of Conversion to Aflibercept for Diabetic Macular Edema Previously Refractory to Bevacizumab or Ranibizumab: A Meta-analysis of High-Quality Nonrandomized Studies

Ann Pharmacother. 2020 Aug;54(8):750-756. doi: 10.1177/1060028020904358. Epub 2020 Jan 31.

Abstract

Background: Aflibercept has been widely used in treating diabetic macular edema (DME). However, the effect of aflibercept in treating DME refractory to bevacizumab or ranibizumab has not been well established. Objective: To assess the therapeutic effect of switching from bevacizumab or ranibizumab to aflibercept in the treatment of refractory DME. Methods: Relevant studies were searched from 3 databases: the Cochrane Library, PubMed, and Web of Science. Data on changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events within the follow-up period were collected and pooled using weighted mean differences (WMDs) with corresponding 95% CIs in a random effects model. The between-study heterogeneity was tested using the χ2 test and the I2 statistic, and funnel plots were used to evaluate the publication bias. Results: A total of 11 nonrandomized trials met the inclusion criteria and were included in the meta-analysis. Our studies showed significant improvements in the BCVA (WMD = 100.55; 95% CI = 68.46 to 132.63; P < 0.01) and reduction in CMT (WMD = 0.09; 95% CI = 0.03 to 0.14; P < 0.01) after switching to aflibercept. Although a large amount of heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed the reliability and stability of our results. Conclusion and Relevance: There were significant improvements in both visual and anatomical outcomes after switching from bevacizumab or ranibizumab to aflibercept, without risk of adverse events. Thus, switching therapy may be a safe and effective treatment for patients with refractory DME.

Keywords: aflibercept; conversion; diabetic macular edema; meta-analysis.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use
  • Diabetes Mellitus / drug therapy*
  • Diabetic Retinopathy / drug therapy*
  • Drug Substitution*
  • Humans
  • Intravitreal Injections
  • Macular Edema / drug therapy*
  • Qualitative Research
  • 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*
  • Reproducibility of Results
  • Treatment Outcome
  • Visual Acuity

Substances

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