Effectiveness and Costs of Bevacizumab vs Ranibizumab in DME
Effectiveness and Costs of Bevacizumab vs Ranibizumab in DME
Diabetic retinopathy (DR) is the most important cause of blindness in the working age population in industrial countries. In patients with DR, diabetic macular edema (DME) is the main cause of permanent decrease of vision. Until recently, the treatment options were focal and grid laser photocoagulation and intra-vitreal injections with corticosteroids, but their efficacy is limited. The recent introduction of the anti-VEGF agent ranibizumab (Lucentis) represents an important improvement in the treatment of DME. Ranibizumab is a Fab fragment of a humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF), a major causal factor in DME.
In several large randomized clinical trials, patients treated with ranibizumab had a better visual outcome than those treated with sham injections and/or laser therapy. Ranibizumab given as monthly injections, or in an 'as needed' scheme, led to a 6–10 letters better mean visual acuity after 12 months compared to control groups. The maximum effect of ranibizumab was observed around 6 months, after which the effect stabilized. In addition to its effect on visual acuity, ranibizumab markedly decreased retinal thickness as measured by optical coherence tomography (OCT) and significantly improved patient reported quality of life parameters.
Bevacizumab (Avastin) is the full length anti-VEGF-A antibody from which ranibizumab is derived. Bevacizumab has been used off-label on a widespread scale by ophthalmologists in the US and Europe, and has gradually become standard care in the treatment of DME in The Netherlands, since the first results of the ranibizumab RCT's became available in 2009. The efficacy and safety of bevacizumab 1.25 mg in the treatment of DME have been demonstrated in a number of case series and two RCTs. Bevacizumab was found to improve visual acuity by approximately 8 letters at 3–12 months follow up. Bevacizumab markedly reduced retinal thickness on OCT, to a similar extent as reported for ranibizumab.
Conclusive evidence from randomized controlled trials (RCT) directly comparing bevacizumab and ranibizumab is lacking.
Nepomuceno et al. recently completed a head to head comparison in 63 eyes. Patients were treated monthly if the central retinal field thickness was more than 275 μm with either bevacizumab or ranizumab for one year. They observed a significant improvement in both groups at all study visits. The improvement was significantly greater in the ranibizumab group compared with the bevacizumab group at week 8 and 32. There was no significant difference in decrease in central retinal thickness. The mean number of injections was significantly higher in the bevacizumab group (9.84) than in the ranibizumab group (7.67).
At this moment two other trials are ongoing. NCT01627249 is a single blind study comparing the effectiveness of intravitreal aflibercept, bevacizumab and ranibizumaf for DME. Six hundred sixty patients will be treated over a one year time frame. The primary outcome is change in BCVA. The secondary outcome is the number of injections.
The other trial, NCT01610557 is a double blind comparison of ranibizumab as monotherapy and ranibizumab and bevacizumab consecutively.
Finally there was a double blind trial, NCT00545870, comparing bevacizumab to ranibizumab for diabetic retinopathy in 60 patients. However it has been suspended.
The costs of bevacizumab are 20 - to 40 fold lower than the costs of ranibizumab, and it has been estimated that in the Netherlands alone, the costs of ranibizumab treatment of DME would be around 10–15 million Euros higher than treatment with bevacizumab.
Background
Diabetic retinopathy (DR) is the most important cause of blindness in the working age population in industrial countries. In patients with DR, diabetic macular edema (DME) is the main cause of permanent decrease of vision. Until recently, the treatment options were focal and grid laser photocoagulation and intra-vitreal injections with corticosteroids, but their efficacy is limited. The recent introduction of the anti-VEGF agent ranibizumab (Lucentis) represents an important improvement in the treatment of DME. Ranibizumab is a Fab fragment of a humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF), a major causal factor in DME.
In several large randomized clinical trials, patients treated with ranibizumab had a better visual outcome than those treated with sham injections and/or laser therapy. Ranibizumab given as monthly injections, or in an 'as needed' scheme, led to a 6–10 letters better mean visual acuity after 12 months compared to control groups. The maximum effect of ranibizumab was observed around 6 months, after which the effect stabilized. In addition to its effect on visual acuity, ranibizumab markedly decreased retinal thickness as measured by optical coherence tomography (OCT) and significantly improved patient reported quality of life parameters.
Bevacizumab (Avastin) is the full length anti-VEGF-A antibody from which ranibizumab is derived. Bevacizumab has been used off-label on a widespread scale by ophthalmologists in the US and Europe, and has gradually become standard care in the treatment of DME in The Netherlands, since the first results of the ranibizumab RCT's became available in 2009. The efficacy and safety of bevacizumab 1.25 mg in the treatment of DME have been demonstrated in a number of case series and two RCTs. Bevacizumab was found to improve visual acuity by approximately 8 letters at 3–12 months follow up. Bevacizumab markedly reduced retinal thickness on OCT, to a similar extent as reported for ranibizumab.
Conclusive evidence from randomized controlled trials (RCT) directly comparing bevacizumab and ranibizumab is lacking.
Nepomuceno et al. recently completed a head to head comparison in 63 eyes. Patients were treated monthly if the central retinal field thickness was more than 275 μm with either bevacizumab or ranizumab for one year. They observed a significant improvement in both groups at all study visits. The improvement was significantly greater in the ranibizumab group compared with the bevacizumab group at week 8 and 32. There was no significant difference in decrease in central retinal thickness. The mean number of injections was significantly higher in the bevacizumab group (9.84) than in the ranibizumab group (7.67).
At this moment two other trials are ongoing. NCT01627249 is a single blind study comparing the effectiveness of intravitreal aflibercept, bevacizumab and ranibizumaf for DME. Six hundred sixty patients will be treated over a one year time frame. The primary outcome is change in BCVA. The secondary outcome is the number of injections.
The other trial, NCT01610557 is a double blind comparison of ranibizumab as monotherapy and ranibizumab and bevacizumab consecutively.
Finally there was a double blind trial, NCT00545870, comparing bevacizumab to ranibizumab for diabetic retinopathy in 60 patients. However it has been suspended.
The costs of bevacizumab are 20 - to 40 fold lower than the costs of ranibizumab, and it has been estimated that in the Netherlands alone, the costs of ranibizumab treatment of DME would be around 10–15 million Euros higher than treatment with bevacizumab.
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