Comparing Ranibizumab with Bevacizumab

Abstract

We conducted a prospective randomized study at 2 tertiary centers in Kolkata, India to compare the efficacy and safety of ranibizumab and bevacizumab in treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration, from January 4, 2007 to January 4, 2009. Investigational review board approval was obtained.Sixty eyes of 60 patients fulfilling all the following inclusion criteria were randomized into 2 equal groups: age >50 years, best corrected visual acuity between 35-70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, classic/occult/subfoveal/juxtafoveal treatment naïve CNV, active leakage on flourescein angiography and central macular thickness (CMT) ≥250 μm (by calipers) as measured using Stratus OCT 3000. Exclusion criteria included 1-eyed patients, macular scar, co-existing ocular pathologies and history of cerebrovascular accident, myocardial infarction or ocular surgery within 6 months.Group A patients were given 3 monthly intravitreal injections of 0.5 mg (in 0.05 ml) ranibizumab and those in Group B received 3 monthly intravitreal injections of 1.25 mg bevacizumab in 0.05 ml. Patients were followed up monthly for 18 months.Repeat injections were given to patients who showed an increase in CMT of more than 100 μm or a decrease in visual acuity by more than 5 ETDRS letters. Eight patients were lost to follow up. Ultimately, Group A had 27 and Group B had 25 cases.The mean number of intravitreal injections required in the ranibizumab group (Group A) was 5.6 and in bevacizumab Group (Group B) was 4.3. Mean visual acuity in Group A increased from 58 ETDRS letters at baseline to 66 ETDRS letters after first 3 monthly ranibizumab injections (P<0.05). The visual acuity at the end of 18 months was 62 ETDRS letters (P = .048) (Figure 1; available at http://aaojournal.org).The mean visual acuity in Group B increased from 57 ETDRS letters at baseline to 64 ETDRS letters after first 3 monthly bevacizumab injections (P<0.05). The visual acuity at the end of 18 months was 61 ETDRS letters (P = .026) (Figure 1; available at http://aaojournal.org).At 18 months, 1 patient (3.7%) lost >15 ETDRS letters in Group A and none lost this many letters in Group B. Increase in visual acuity was recorded in 23 patients (85.2%) in Group A, and 21 patients (84%) in Group B at 18 months. Seven patients (25.9%) gained >15 letters in Group A and 3 (12%) in Group B at 18 months.The average CMT in Group A decreased from 289 μm at baseline to a low of 204 μm at the end of month 4 (P<0.05). The average CMT at the end of 18th month in this group was 244 μm (P<0.05). Similarly, the average CMT in Group B decreased from 284 μm at baseline to a low of 202 μm at month 4 (P<0.05). The average CMT at the end of 18th month was 246 μm (P<0.05). Thus, there was a statistically significant decrease in CMT in both the groups postinjection and the statistically significant decrease was maintained over 18 months (Figure 2; available at http://aaojournal.org).Landa et al1Landa G. Amde W. Doshi V. et al.Comparative study of intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) in the treatment of neovascular age-related macular degeneration.Ophthalmologica. 2009; 223: 370-375Crossref PubMed Scopus (56) Google Scholar and Rosenfeld et al2Stepien K.E. Rosenfeld P.J. Puliafito C.A. et al.Comparison of intravitreal bevacizumab followed by ranibizumab for the treatment of neovascular age-related macular degeneration.Retina. 2009; 29: 1067-1073Crossref PubMed Scopus (40) Google Scholar concluded that there is no significant difference in the efficacies of ranibizumab and bevacizumab. Chang et al,3Chang T.S. Kokame G. Casey R. et al.Short-term effectiveness of intravitreal bevacizumab versus ranibizumab 20 injections for patients with neovascular age-related macular degeneration.Retina. 2009; 29: 1235-1241Crossref PubMed Scopus (20) Google Scholar in their retrospective comparative study, concluded that short-term effectiveness of ranibizumab is significantly greater than bevacizumab. The complete results of Inhibit VEGF in Age-related choroidal Neovascularisation Trial, the Comparison of Age-Related Macular Degeneration Treatments Trials and other similar ongoing studies are awaited.In our prospective study, no statistically significant difference was found in terms of change in visual acuity or CMT (P>0.05) between ranibizumab or bevacizumab groups at the end of 3rd, 6th, 12th, and 18th months (Table 1, Table 2; available at http://aaojournal.org). Despite the relatively small sample size, the improvement in visual acuity and CMT appear strikingly similar in both groups. No significant safety concerns were identified with either drug. We conducted a prospective randomized study at 2 tertiary centers in Kolkata, India to compare the efficacy and safety of ranibizumab and bevacizumab in treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration, from January 4, 2007 to January 4, 2009. Investigational review board approval was obtained. Sixty eyes of 60 patients fulfilling all the following inclusion criteria were randomized into 2 equal groups: age >50 years, best corrected visual acuity between 35-70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, classic/occult/subfoveal/juxtafoveal treatment naïve CNV, active leakage on flourescein angiography and central macular thickness (CMT) ≥250 μm (by calipers) as measured using Stratus OCT 3000. Exclusion criteria included 1-eyed patients, macular scar, co-existing ocular pathologies and history of cerebrovascular accident, myocardial infarction or ocular surgery within 6 months. Group A patients were given 3 monthly intravitreal injections of 0.5 mg (in 0.05 ml) ranibizumab and those in Group B received 3 monthly intravitreal injections of 1.25 mg bevacizumab in 0.05 ml. Patients were followed up monthly for 18 months. Repeat injections were given to patients who showed an increase in CMT of more than 100 μm or a decrease in visual acuity by more than 5 ETDRS letters. Eight patients were lost to follow up. Ultimately, Group A had 27 and Group B had 25 cases. The mean number of intravitreal injections required in the ranibizumab group (Group A) was 5.6 and in bevacizumab Group (Group B) was 4.3. Mean visual acuity in Group A increased from 58 ETDRS letters at baseline to 66 ETDRS letters after first 3 monthly ranibizumab injections (P<0.05). The visual acuity at the end of 18 months was 62 ETDRS letters (P = .048) (Figure 1; available at http://aaojournal.org). The mean visual acuity in Group B increased from 57 ETDRS letters at baseline to 64 ETDRS letters after first 3 monthly bevacizumab injections (P<0.05). The visual acuity at the end of 18 months was 61 ETDRS letters (P = .026) (Figure 1; available at http://aaojournal.org). At 18 months, 1 patient (3.7%) lost >15 ETDRS letters in Group A and none lost this many letters in Group B. Increase in visual acuity was recorded in 23 patients (85.2%) in Group A, and 21 patients (84%) in Group B at 18 months. Seven patients (25.9%) gained >15 letters in Group A and 3 (12%) in Group B at 18 months. The average CMT in Group A decreased from 289 μm at baseline to a low of 204 μm at the end of month 4 (P<0.05). The average CMT at the end of 18th month in this group was 244 μm (P<0.05). Similarly, the average CMT in Group B decreased from 284 μm at baseline to a low of 202 μm at month 4 (P<0.05). The average CMT at the end of 18th month was 246 μm (P<0.05). Thus, there was a statistically significant decrease in CMT in both the groups postinjection and the statistically significant decrease was maintained over 18 months (Figure 2; available at http://aaojournal.org). Landa et al1Landa G. Amde W. Doshi V. et al.Comparative study of intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) in the treatment of neovascular age-related macular degeneration.Ophthalmologica. 2009; 223: 370-375Crossref PubMed Scopus (56) Google Scholar and Rosenfeld et al2Stepien K.E. Rosenfeld P.J. Puliafito C.A. et al.Comparison of intravitreal bevacizumab followed by ranibizumab for the treatment of neovascular age-related macular degeneration.Retina. 2009; 29: 1067-1073Crossref PubMed Scopus (40) Google Scholar concluded that there is no significant difference in the efficacies of ranibizumab and bevacizumab. Chang et al,3Chang T.S. Kokame G. Casey R. et al.Short-term effectiveness of intravitreal bevacizumab versus ranibizumab 20 injections for patients with neovascular age-related macular degeneration.Retina. 2009; 29: 1235-1241Crossref PubMed Scopus (20) Google Scholar in their retrospective comparative study, concluded that short-term effectiveness of ranibizumab is significantly greater than bevacizumab. The complete results of Inhibit VEGF in Age-related choroidal Neovascularisation Trial, the Comparison of Age-Related Macular Degeneration Treatments Trials and other similar ongoing studies are awaited. In our prospective study, no statistically significant difference was found in terms of change in visual acuity or CMT (P>0.05) between ranibizumab or bevacizumab groups at the end of 3rd, 6th, 12th, and 18th months (Table 1, Table 2; available at http://aaojournal.org). Despite the relatively small sample size, the improvement in visual acuity and CMT appear strikingly similar in both groups. No significant safety concerns were identified with either drug. AppendixFigure 2Change in average central macular thickness (Microns) in Ranibizumab Group (Group A, n=27) and Bevacizumab Group (Group B, n=25).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 1Comparison of Change in Visual Acuity (VA in ETDRS Letters) RANIBIZUMAB Group (Group A) Vs. BEVACIZUMAB Group (Group B): Test of Significance: T-TestRANIBIZUMABBEVACIZUMABp-valueNMeanStandard DeviationNMeanStandard DeviationPair 1Mean Change in Visual Acuity at Month 3275.825.73254.925.720.76Pair 2Mean Change in Visual Acuity at Month 6275.749.01255.927.560.82Pair 3Mean Change in Visual Acuity at Month 12273.228.29250.5210.970.46Pair 4Mean Change in Visual Acuity at Month 18273.568.90253.968.360.56ETDRS - Early Treatment Diabetic Retinopathy Study. Open table in a new tab Table 2Comparison of Mean Change in Central Macular Thickness (CMT in microns) RANIBIZUMAB Group (Group A) Vs. BEVACIZUMAB Group (Group B): Test of Significance: T-TestRANIBIZUMABBEVACIZUMABp-valueNMeanStandard DeviationNMeanStandard DeviationPair 1Mean Change in CMT at Month 327−71.5627.7825−74.1621.740.35Pair 2Mean Change in CMT at Month 627−56.2647.6725−58.7234.550.16Pair 3Mean Change in CMT at Month 1227−27.5946.4525−26.4440.550.28Pair 4Mean Change in CMT at Month 1827−44.7066.5625−37.9655.330.28CMT-Central Macular Thickness (measured in microns). Open table in a new tab ETDRS - Early Treatment Diabetic Retinopathy Study. CMT-Central Macular Thickness (measured in microns).