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Original ArticleFree Preview

Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema

List of authors.
  • Chirag D. Jhaveri, M.D.,
  • Adam R. Glassman, M.S.,
  • Frederick L. Ferris, III, M.D.,
  • Danni Liu, M.S.P.H.,
  • Maureen G. Maguire, Ph.D.,
  • John B. Allen, M.D.,
  • Carl W. Baker, M.D.,
  • David Browning, M.D., Ph.D.,
  • Matthew A. Cunningham, M.D.,
  • Scott M. Friedman, M.D.,
  • Lee M. Jampol, M.D.,
  • Dennis M. Marcus, M.D.,
  • Daniel F. Martin, M.D.,
  • Carin M. Preston, M.P.H.,
  • Cynthia R. Stockdale, M.S.P.H.,
  • and Jennifer K. Sun, M.D., M.P.H.
  • for the DRCR Retina Network*

Abstract

Background

In eyes with diabetic macular edema, the relative efficacy of administering aflibercept monotherapy as compared with bevacizumab first with a switch to aflibercept if the eye condition does not improve sufficiently (a form of step therapy) is unclear.

Methods

Download a PDF of the Research Summary.

At 54 clinical sites, we randomly assigned eyes in adults who had diabetic macular edema involving the macular center and a visual-acuity letter score of 24 to 69 (on a scale from 0 to 100, with higher scores indicating better visual acuity; Snellen equivalent, 20/320 to 20/50) to receive either 2.0 mg of intravitreous aflibercept or 1.25 mg of intravitreous bevacizumab. The drug was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met. The primary outcome was the mean change in visual acuity over the 2-year trial period. Retinal central subfield thickness and visual acuity at 2 years and safety were also assessed.

Results

A total of 312 eyes (in 270 adults) underwent randomization; 158 eyes were assigned to receive aflibercept monotherapy and 154 to receive bevacizumab first. Over the 2-year period, 70% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. The mean improvement in visual acuity was 15.0 letters in the aflibercept-monotherapy group and 14.0 letters in the bevacizumab-first group (adjusted difference, 0.8 letters; 95% confidence interval, −0.9 to 2.5; P=0.37). At 2 years, the mean changes in visual acuity and retinal central subfield thickness were similar in the two groups. Serious adverse events (in 52% of the patients in the aflibercept-monotherapy group and in 36% of those in the bevacizumab-first group) and hospitalizations for adverse events (in 48% and 32%, respectively) were more common in the aflibercept-monotherapy group.

Conclusions

In this trial of treatment of moderate vision loss due to diabetic macular edema involving the center of the macula, we found no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response. (Funded by the National Institutes of Health; Protocol AC ClinicalTrials.gov number, NCT03321513.)

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Aflibercept or Bevacizumab First for Diabetic Macular Edema
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Funding and Disclosures

Supported by a grant (UG1EY014231) from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

This article was published on July 14, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Author Affiliations

From the Retina Consultants of Austin and the Austin Research Center for Retina — both in Austin, TX (C.D.J.); the Jaeb Center for Health Research, Tampa (A.R.G., D.L., M.G.M., C.M.P., C.R.S.), the Florida Retina Institute, Orlando (M.A.C.), and Florida Retina Consultants, Lakeland (S.M.F.) — all in Florida; Ophthalmic Research Consultants, Waxhaw (F.L.F.), and Southeast Clinical Research Associates (J.B.A.) and Charlotte Eye, Ear, Nose, and Throat Associates (D.B.), Charlotte — all in North Carolina; the Ophthalmology Group, Paducah, KY (C.W.B.); the Feinberg School of Medicine, Northwestern University, Chicago (L.M.J.); the Southeast Retina Center, Augusta, GA (D.M.M.); Cole Eye Institute, Cleveland Clinic, Cleveland (D.F.M.); and the Joslin Diabetes Center, Beetham Eye Institute, and the Department of Ophthalmology, Harvard Medical School, Boston (J.K.S.).

Mr. Glassman can be contacted at or at the Jaeb Center for Health Research, 15310 Amberly Dr., Suite 350, Tampa, FL 33647.

A list of the members of the DRCR Retina Network is provided in the Supplementary Appendix, available at NEJM.org.

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