Clinical Outcomes of a Treat and Extend Regimen with Intravitreal Aflibercept Injections in Patients with Diabetic Macular Edema: Experience in Clinical Practice

Abstract

Introduction

Treat-and-extend (T&E) and pro re nata (PRN; ‘as needed’) regimens of intravitreal anti-vascular endothelial growth factor (VEGF) treatment have been found to reduce the injection burden on patients and improve the cost effectiveness of the treatment of macular edema. The aim of this study was to assess the effectiveness of a T&E regimen of aflibercept, in a clinical setting, in patients with diabetic macular edema (DME) who were either intravitreal anti-VEGF therapy naive or with minimal exposure to anti-VEGF (≤ 6 treatments) in the previous 12 months.

Methods

This prospective, single arm, open label study recruited patients with DME (macular thickness of ≥ 300 µm) and best-corrected visual acuity (BCVA) between 28-78 ETDRS letters. Participants received five loading doses of intravitreal aflibercept at 4-weekly intervals. BCVA measurements and macular optical coherence tomography were performed at each visit. If no disease activity was detected, treatment intervals were increased by 2 weeks to a maximum of 12 weeks. Outcome measures included: changes in BCVA and retinal anatomical measures (central foveal thickness [CFT] and central macular volume within 6 mm of the fovea [CSVol]) between baseline and 2 years, patient treatment intervals; and adverse events.

Results

Of the 36 patients who provided informed consent to participate in the study and were screened, 26 patients (eyes) were eligible to participate in the study. After regression analysis, adjustment for repeated measures, and significant covariates, the mean BCVA increased by 3.8 letters (95% confidence interval [CI] 1.1, 6.4) and the CFT and CSVol decreased by 127.2 µm (95% CI 91.7, 162.5) and 1.6 mm3 (95% CI 1.2, 2.0), respectively, over the course of the study. In the second year, 16 of the 25 patients still participating had their treatment intervals extended to 12 weeks. There was no evidence of any new adverse events that would require changes to the aflibercept safety profile.

Conclusion

For the majority of patients presenting with DME, a T&E regimen of aflibercept in the first 2 years of therapy is a practical alternative to PRN treatment with regular review.

Trial Registration

Australian New Zealand Clinical Trials Registry number, ACTRN12618000428268.

Funding

This investigator-initiated study was supported by Bayer Australia Ltd. who provided the study treatment and some financial assistance.

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Acknowledgments

We are grateful to the patients who participated in this study. Thanks also to Dr Guy Bylsma and Dr Andrew Traill who, along with Clinical Professor Nitin Verma and Professor Alex Hewitt, were Clinical Investigators on this study and provided advice on the study protocol in addition to identifying and caring for study participants.

Funding

This investigator-initiated study was supported by Bayer Australia Ltd. who provided the study treatment and some financial assistance but did not contribute to the study design, analysis, or preparation of this manuscript. No funding was received for the publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors criteria for authorship of this article, take responsibility for the integrity of the work as a whole, and have given their approval for publication of this version.

Disclosures

Beverley A. Curry, Paul G. Sanfilippo, Sarah Chan, Alexander W. Hewitt, and Nitin Verma have nothing to declare.

Compliance with Ethics Guidelines

Institutional ethics approval was obtained from the Tasmanian Health and Medical Research Ethics Committee (THMREC) prior to study commencement, Protocol Ref No: H0014556 and registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12618000428268. Informed consent was obtained from all participants, prior to enrolment, in accordance with Springer’s ethical policies. The study adhered to the tenets of the 1964 Declaration of Helsinki, as revised in 2013, and to the protocol approved by THMREC.

Data Availability

The de-identified participant datasets analysed in preparation of this manuscript may be available from the corresponding author if a reasonable request is received and the research study proposed has ethical approval.

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Correspondence to Beverley A. Curry.

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Curry, B.A., Sanfilippo, P.G., Chan, S. et al. Clinical Outcomes of a Treat and Extend Regimen with Intravitreal Aflibercept Injections in Patients with Diabetic Macular Edema: Experience in Clinical Practice. Ophthalmol Ther 9, 87–101 (2020). https://doi.org/10.1007/s40123-019-00224-x

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Keywords

  • Aflibercept
  • Anti-vascular endothelial growth factor
  • Clinical setting
  • Diabetic macular oedema
  • Treat and extend