Original article
Intravitreal Aflibercept Injection for Macular Edema Secondary to Central Retinal Vein Occlusion: 1-Year Results From the Phase 3 COPERNICUS Study

https://doi.org/10.1016/j.ajo.2012.09.026Get rights and content

Purpose

To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO).

Methods

This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52.

Results

At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure.

Conclusions

Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated.

Section snippets

Methods

The COPERNICUS study is an ongoing 2-year, phase 3, prospective, randomized, double-masked trial. This multicenter study was conducted across 70 sites in the United States, Canada, Colombia, India, and Israel. The study protocol of the COPERNICUS trial was approved by the institutional review board or ethics committee at each participating clinical center before the start of the study. This trial was registered with ClinicalTrials.gov (identifier #NCT00943072). All patients signed a written

Patient Disposition

A total of 189 patients were randomized to intravitreal aflibercept 2Q4 + PRN (n = 115) and sham + IAI PRN (n = 74). With the exception of 1 patient in the IAI 2Q4 + PRN group, all randomized patients received study drugs. The majority of patients (57/74, 77.0% sham + IAI PRN and 107/115, 93.0% IAI 2Q4 + PRN) completed the first 52 weeks of the study (Supplemental Figure 2, available at AJO.com). The primary reasons for premature discontinuation from the study before week 52 were withdrawal of

Discussion

The COPERNICUS study results from week 24 through week 52 demonstrate that the robust elimination of retinal edema on OCT and the concomitant BCVA gains achieved after 6 monthly intravitreal aflibercept injections in the IAI 2Q4group can be largely maintained with less frequent dosing of a mean 2.7 injections. It must be noted that patients continued to be evaluated monthly during the PRN phase. Careful monitoring in clinical practice may be critical to achieve this result in a reactive PRN

David M. Brown, a graduate of Baylor College of Medicine, is a retina specialist in Retina Consultants of Houston, Texas, and directs one of the largest clinical trial centers for retinal disease in the United States. His research and clinical interests are focused on macular surgery, AMD, and diabetic retinopathy. Dr Brown has published and written over 150 national meeting presentations, abstracts, and scientific papers, including many of the primary papers on anti-VEGF agents.

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David M. Brown, a graduate of Baylor College of Medicine, is a retina specialist in Retina Consultants of Houston, Texas, and directs one of the largest clinical trial centers for retinal disease in the United States. His research and clinical interests are focused on macular surgery, AMD, and diabetic retinopathy. Dr Brown has published and written over 150 national meeting presentations, abstracts, and scientific papers, including many of the primary papers on anti-VEGF agents.

Julia Haller, MD, is Ophthalmologist-in-Chief and the William Tasman, Endowed Chair in Ophthalmology at Wills Eye Institute, Philadelphia, Pennsylvania. She also serves as Professor and Chair of the Department of Ophthalmology at Jefferson Medical College of Thomas Jefferson University. Her primary research interests are retinal detachments, macular surgery, RVO, AMD, posterior segment inflammatory diseases, and diabetic retinopathy. Dr Haller has published over 250 peer-reviewed articles and is on the editorial board of 8 journals.

Supplemental Material available at AJO.com

See Accompanying Editorial on page 415.

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