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A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema

Graefe's Archive for Clinical and Experimental Ophthalmology volume 255, pages 463–473 (2017)Cite this article

Abstract

Purpose

To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME).

Methods

This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography.

Results

Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was −4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p < 0.001); the decrease in fluorescein leakage area was greater with DEX implant than ranibizumab at month 12 (p < 0.001). Ocular adverse events in the study eye were more frequent in the DEX implant group because of the occurrence of intraocular pressure (IOP) increases and cataract. IOP increases were transient and generally managed with topical medication.

Conclusions

Both DEX implant and ranibizumab were well tolerated and improved BCVA and anatomic outcomes in patients with DME. DEX implant met the a priori criterion for noninferiority to ranibizumab in average change from baseline BCVA over 12 months. Noninferiority was achieved with an average of 2.85 DEX implant injections and 8.70 ranibizumab injections per patient.

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Acknowledgments

Medical writing assistance was provided to the authors by Jamie L Weiss, PhD, Allergan plc, Bridgewater, NJ, USA and funded by Allergan plc. We thank Amelia Orejudos, MSc, Allergan plc, Bridgewater, NJ, USA for statistical consultation on the manuscript. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship.

Author information

Affiliations

  1. Texas Retina Associates, 801 W Randol Mill Rd, Suite 101, Arlington, TX, 76012, USA

    David G. Callanan

  2. Tel Aviv Medical Center, Tel Aviv, Israel

    Anat Loewenstein

  3. West Texas Retina, Abilene, TX, USA

    Sunil S. Patel

  4. Paris Diderot University, Lariboisière Hospital, Paris, France

    Pascale Massin

  5. Institute of Ocular Microsurgery, Barcelona, Spain

    Borja Corcóstegui

  6. Allergan plc, Irvine, CA, USA

    Xiao-Yan Li, Jenny Jiao & Yehia Hashad

  7. Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Scott M. Whitcup

Authors
  1. David G. Callanan
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  2. Anat Loewenstein
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  4. Pascale Massin
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  9. Scott M. Whitcup
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Corresponding author

Correspondence to David G. Callanan.

Ethics declarations

Funding and competing interests

This study was sponsored by Allergan plc (Dublin, Ireland).

David G. Callanan is a consultant to Alcon, Allergan, Regeneron, and Santen and is on the speakers’ bureau of Allergan.

Anat Loewenstein is a consultant to Alcon, Allergan, Bayer, Novartis, and Notal Vision.

Sunil S. Patel has received research grants from Alcon, Allegro, Allergan, Astellas, Genentech, Ophthotech, and Regeneron.

Pascale Massin is a consultant to Alimera, Allergan, Bayer, Novartis, and Sanofi.

Borja Corcóstegui has received speaker fees from Allergan, Bausch & Lomb, and Bayer.

Xiao-Yan Li, Jenny Jiao, and Yehia Hashad are employees of Allergan plc. Scott M. Whitcup is a consultant to Allergan and was formerly employed by Allergan. The authors have full control of all primary data, and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

The study is registered with the identifier NCT01492400 at ClinicalTrials.gov.

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Callanan, D.G., Loewenstein, A., Patel, S.S. et al. A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 255, 463–473 (2017). https://doi.org/10.1007/s00417-016-3472-1

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  • DOI: https://doi.org/10.1007/s00417-016-3472-1

Keywords

  • Dexamethasone
  • Diabetic macular edema
  • Intravitreal
  • Noninferiority
  • Randomized clinical trial
  • Ranibizumab