Ranibizumab or Bevacizumab in Patients With Neovascular AMD
Ranibizumab or Bevacizumab in Patients With Neovascular AMD
Aim The current accepted standard treatment for neovascular age-related macular degeneration (AMD) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab. The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity.
Methods In this prospective randomised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres. Patients were randomised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab. Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion. Re-treatment was scheduled as needed. Outcome measures were early treatment of diabetic retinopathy visual acuity, retinal thickness, lesion size and safety evaluation.
Results A total of 321 patients were recruited of which four had to be excluded due to different reasons. Of the 317 remaining patients 154 were randomised into the bevacizumab group and 163 into the ranibizumab group. At month 12, there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group (p=0.78). Furthermore, there were no significant differences in the decrease of retinal thickness, change of lesion size and number of adverse events between the groups.
Conclusions Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year. There was no significant difference of decrease of retinal thickness or number of adverse events.
The healthcare systems of the Western world are confronted with an increasing number of patients suffering from age-related macular degeneration (AMD). Friedman et al estimated an increase of 50% of the number of individuals suffering from AMD in the USA up to the year 2020. Although the neovascular form of AMD accounts for only 20% of the cases with AMD, it is responsible for 90% of the cases of legal blindness. In recent years, significant advances in the treatment of neovascular AMD have been achieved. In contrast to prior treatments such as argon laser photocoagulation and photodynamic therapy (PDT), modern approaches with inhibitors of anti-VEGF (vascular endothelial growth factor) are not limited by lesion composition and lesion size. Treatment with the anti-VEGF agents ranibizumab and bevacizumab has become the mainstay of the treatment of neovascular AMD. Ranibizumab (Lucentis) was approved in this indication by the Food and Drug Administration and by the European Medicines Agency. Bevacizumab (Avastin) was approved for the therapy of colorectal cancer but is frequently used off label for intravitreal injection. The active part of the antibody is similar in ranibizumab and bevacizumab. However, there are a series of differences with a possible impact on safety and effect of the treatment. The antibody fragment ranibizumab is smaller (48 kD) than the whole anti-VEGF bevacizumab (150 kD). In comparison with bevacizumab, ranibizumab provides a shorter half-lifetime, lower serum concentrations, a better penetration through the retina and a several-fold binding to VEGF-A. Furthermore, the costs of one injection of ranibizumab may reach 50 times that of bevacizumab.
Large multicentre studies have proven that monthly applied ranibizumab is effective and safe in the treatment of neovascular AMD. In clinical practice, frequently as needed regimen (pro re nata (PRN)) was applied, which has been proven to be effective. For bevacizumab, a series of smaller studies with a lower evidence level have shown the efficacy of the therapy, most commonly applied in a PRN regimen and two recent multicentre studies have shown non-inferiority over ranibizumab.
Abstract and Introduction
Abstract
Aim The current accepted standard treatment for neovascular age-related macular degeneration (AMD) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab. The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity.
Methods In this prospective randomised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres. Patients were randomised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab. Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion. Re-treatment was scheduled as needed. Outcome measures were early treatment of diabetic retinopathy visual acuity, retinal thickness, lesion size and safety evaluation.
Results A total of 321 patients were recruited of which four had to be excluded due to different reasons. Of the 317 remaining patients 154 were randomised into the bevacizumab group and 163 into the ranibizumab group. At month 12, there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group (p=0.78). Furthermore, there were no significant differences in the decrease of retinal thickness, change of lesion size and number of adverse events between the groups.
Conclusions Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year. There was no significant difference of decrease of retinal thickness or number of adverse events.
Introduction
The healthcare systems of the Western world are confronted with an increasing number of patients suffering from age-related macular degeneration (AMD). Friedman et al estimated an increase of 50% of the number of individuals suffering from AMD in the USA up to the year 2020. Although the neovascular form of AMD accounts for only 20% of the cases with AMD, it is responsible for 90% of the cases of legal blindness. In recent years, significant advances in the treatment of neovascular AMD have been achieved. In contrast to prior treatments such as argon laser photocoagulation and photodynamic therapy (PDT), modern approaches with inhibitors of anti-VEGF (vascular endothelial growth factor) are not limited by lesion composition and lesion size. Treatment with the anti-VEGF agents ranibizumab and bevacizumab has become the mainstay of the treatment of neovascular AMD. Ranibizumab (Lucentis) was approved in this indication by the Food and Drug Administration and by the European Medicines Agency. Bevacizumab (Avastin) was approved for the therapy of colorectal cancer but is frequently used off label for intravitreal injection. The active part of the antibody is similar in ranibizumab and bevacizumab. However, there are a series of differences with a possible impact on safety and effect of the treatment. The antibody fragment ranibizumab is smaller (48 kD) than the whole anti-VEGF bevacizumab (150 kD). In comparison with bevacizumab, ranibizumab provides a shorter half-lifetime, lower serum concentrations, a better penetration through the retina and a several-fold binding to VEGF-A. Furthermore, the costs of one injection of ranibizumab may reach 50 times that of bevacizumab.
Large multicentre studies have proven that monthly applied ranibizumab is effective and safe in the treatment of neovascular AMD. In clinical practice, frequently as needed regimen (pro re nata (PRN)) was applied, which has been proven to be effective. For bevacizumab, a series of smaller studies with a lower evidence level have shown the efficacy of the therapy, most commonly applied in a PRN regimen and two recent multicentre studies have shown non-inferiority over ranibizumab.