Elsevier

Ophthalmology

Volume 119, Issue 7, July 2012, Pages 1388-1398
Ophthalmology

Original article
Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: Two-Year Results

https://doi.org/10.1016/j.ophtha.2012.03.053Get rights and content

Objective

To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.

Design

Multicenter, randomized clinical trial.

Participants

Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.

Interventions

At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.

Main Outcome Measures

Mean change in visual acuity.

Results

Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, −1.4 letters; 95% confidence interval [CI], −3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, −2.4 letters; 95% CI, −4.8 to −0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (−2.2 letters; P = 0.03) and a lower proportion without fluid (−19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07−1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).

Conclusions

Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Population

The design and methods for CATT have been published previously.4 Eligible eyes had active choroidal neovascularization secondary to AMD, no previous treatment, visual acuity between 20/25 and 20/320, and neovascularization, fluid, or hemorrhage under the fovea. The study was approved by an institutional review board associated with each center. The study adhered to the tenets of the Declaration of Helsinki and was performed in compliance with the Health Insurance Portability and Accountability

Patients and Treatment

At enrollment, there were no substantial imbalances in demographic or ocular characteristics among the 6 treatment groups (Table 1). Two years after enrollment, visual acuity scores were available for 1030 of 1107 patients (93.0%). Missed visit rates at 2 years were similar across treatment groups (3.0%−5.0%). Additional information about follow-up may be found in Appendix 2 (available at http://aaojournal.org).

Treatment decisions by ophthalmologists in year 2 were consistent with the

Discussion

At both 1 and 2 years, bevacizumab and ranibizumab had similar effects on visual acuity when the dosing regimen was the same (Fig 2; Table 2, Table 3). There was little difference in any visual metric evaluated, including mean gain in visual acuity, the proportion of patients who gained 3 lines, the proportion of patients who did not lose 3 lines, and the proportion of patients who achieved 20/40 or better visual acuity. Mean gains in visual acuity at 2 years were within 1.4 letters, and the

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Cited by (0)

Manuscript no. 2012-429.

The members of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group are listed in Appendix 1 (available at http://aaojournal.org).

Financial Disclosure(s): The author(s) have made the following disclosure(s):

Glenn J. Jaffe - Consultant - Heidelberg Engineering; Financial support - Regeneron

Cynthia Toth - Consultant - Physical Sciences Incorporated; Financial support - Genentech, Bioptigen, and Physical Sciences Incorporated; Patents pending - OCT analysis technology related to analysis for age-related macular degeneration; Royalties - Alcon Laboratories for ophthalmic surgical technologies

Dr. Jaffe's and Dr. Toth's institution receives money for these relationships. The other members of the writing committee have no financial relationships to declare.

Financial Support: Supported by cooperative agreements U10 EY017823, U10 EY017825, U10 EY017826, and U10 EY017828 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services. The funding organization participated in the design and conduct of the study, data analysis and interpretation, and review of the manuscript.

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Group members listed online in Appendix 1 (available at http://aaojournal.org).

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