Effectiveness of Continued Ranibizumab Therapy in Neovascular Age-Related Macular Degeneration versus Switch to Aflibercept: Real World Evidence

Ophthalmol Retina. 2019 Jan;3(1):8-15.e1. doi: 10.1016/j.oret.2018.09.001. Epub 2018 Sep 15.

Abstract

Purpose: To assess the long-term comparative effectiveness of ranibizumab versus switching to aflibercept in neovascular age-related macular degeneration (nAMD).

Design: A 24-month, retrospective, comparative, nonrandomized, matched cohort study.

Participants: Patients with nAMD initiated on ranibizumab who remained (nonswitchers) or who switched to aflibercept (switchers) captured from a United States electronic medical records database between July 1, 2011 and October 12, 2014.

Methods: Patient eyes were matched for baseline age, baseline visual acuity (VA), VA at month 3, and duration of follow-up. Matching ratio was 1:2 (switchers: nonswitchers) where possible and 1:1 otherwise.

Main outcome measures: The primary outcome was VA change from baseline (first injection of ranibizumab) to month 24. Secondary end points were standardized area under the curve of VA change; patient eyes (%) gaining or losing ≥5, ≥10, or ≥15 letters, or with VA of >73 letters at month 24; number of injections and monitoring visits; and analysis of preswitch characteristics.

Results: A total of 454 switchers and 750 matched nonswitchers were included. The adjusted difference in mean VA change from baseline to month 24 for switchers to nonswitchers was 0.02 letters (95% confidence interval [CI], -1.63 to 1.68). The upper bound 95% CI (1.68) was below the predefined noninferiority margin of 5 letters. Switchers had a significantly higher annualized number of mean total visits compared with nonswitchers (10.0 vs. 9.0 for year 1; 8.7 vs. 7.4 for year 2), a higher number of injection visits (8.4 vs. 6.7 for year 1; 7.0 vs. 5.1 for year 2), but a lower number of monitoring-only visits (1.6 vs. 2.3 for year 1; 1.7 vs. 2.3 for year 2). During the preswitch period, switchers had a higher number of injection visits (7.6 vs. 6.5), fewer monitoring-only visits (1.5 vs. 2.2), and comparable total visits (9.1 vs. 8.7). Visual acuity change from baseline to switch was similar between switchers and nonswitchers (adjusted least squares mean difference, -1.36 letters; 95% CI, -2.76 to 0.05).

Conclusions: Switching patients from ranibizumab to aflibercept resulted in no difference in VA change compared with those maintained on ranibizumab only. The lower retreatment rate in nonswitchers compared with switchers post switch does not support the view of a longer treatment efficacy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Substitution
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Male
  • Ranibizumab / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Recombinant Fusion Proteins / administration & dosage*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Visual Acuity*
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*

Substances

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