Ranibizumab vs Bevacizumab: Findings From the IVAN Trial

Aarika L. Menees, MD; Sophie J. Bakri, MD


December 17, 2012

Ranibizumab Versus Bevacizumab to Treat Neovascular Age-Related Macular Degeneration: One-Year Findings From the IVAN Randomized Trial

IVAN Study Investigators, Chakravarthy U, Harding SP, Rogers CA, et al
Ophthalmology. 2012;119:1399-1411

Study Summary

The Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN) trial, performed in the United Kingdom, was a multicenter randomized noninferiority factorial trial with equal allocation of participants to 4 groups and the noninferiority limit set to 3.5 letters. Participants (610 patients) were older than 50 years of age and had untreated neovascular age-related macular degeneration (nAMD) confirmed by fluorescein angiography. One eye was used per patient and the study eye read 25 or more letters on the Early Treatment Diabetic Retinopathy Study chart.

Interventions for the study were 0.5 mg ranibizumab or 1.25 mg bevacizumab. Patients received a monthly clinical examination, optical coherence tomography, and fundus photographs. After a set of 3 injections, the patients were divided into continuous therapy (monthly) or discontinuous therapy (as needed with monthly review) groups for each intervention. The primary efficacy and safety outcome measures were distance visual acuity, arteriothrombotic events, and heart failure. The study found that the mean difference in visual acuities favored ranibizumab by 2 letters, but the difference was not clinically significant. In addition, continuous treatment was found to be equivalent to discontinuous treatment in regard to visual acuity. Fewer patients in the bevacizumab group experienced arteriothrombotic events or heart failure compared with the ranibizumab group (0.7% vs 2.9%; odds ratio, 0.23; 95% confidence interval, 0.05-1.07; P =.03). No differences were found between continuous and discontinuous regimens.

A unique secondary measure in this study was assessment of median serum vascular endothelial growth factor (VEGF) concentrations. At 1 year, patients in all groups had a lower median serum VEGF concentration compared with baseline values. Of note, serum concentrations of VEGF were lower for bevacizumab than for ranibizumab and were higher for discontinuous than continuous treatment.

Cost analysis was performed for annual costs per patient, which included testing, drug costs, and treatments for adverse events. Not surprisingly, the continuous ranibizumab treatment was found to be most expensive, followed by discontinuous ranibizumab, then continuous bevacizumab, and finally discontinuous bevacizumab. The difference between continuous and discontinuous bevacizumab was not clinically significant.


The strengths of this study include a multicenter randomized clinical design, a large sample size, and 1-year follow-up. The study attempted to help to further delineate the differences among ranibizumab, bevacizumab, continuous, and discontinuous treatment of nAMD. The data at 1 year did not establish which treatment modality is superior because no clinically significant difference in visual outcome was found. Further data at 2 years may help to determine whether one treatment modality is superior to the other over a longer treatment period. The results at 2 years may offer a correlation among treatment modalities, serum VEGF concentrations, and adverse events. Furthermore, they may provide insight into the long-term effects of these modalities, which are currently unknown.