Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration

Institute of Clinical Science, The Queen's University of Belfast, Belfast, Ireland.
Ophthalmology (Impact Factor: 6.14). 05/2012; 119(7):1399-411. DOI: 10.1016/j.ophtha.2012.04.015
Source: PubMed


To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).
Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).
People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart.
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.
Proprietary or commercial disclosures may be found after the references.

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Available from: Barnaby Reeves, Dec 13, 2013
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    • "To date, only limited experimental data and studies comparing the effects of bevacizumab and ranibizumab have been published. The comparative trials CATT and IVAN evaluated the therapeutic efficacy of bevacizumab compared with ranibizumab, concluding that the former was not inferior to the latter [12, 13]. "
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    ABSTRACT: Background Ranibizumab (Lucentis®) is a Fab-antibody fragment developed from Bevacizumab, a full-length anti-VEGF antibody. Both compounds are used for treating age-related macular degeneration (AMD). The influence of bevacizumab and ranibizumab on genes involved in signal transduction and cell signaling downstream of VEGF were compared in order to detect possible differences in their mode of action, which are not related to their Fab-antibody fragments. Methods Human umbilical vein cell lines (EA.hy926) and retinal pigment epithelial cells (ARP-19) were exposed to oxidative stress. The cells were treated with therapeutic concentrations of bevacizumab (0.25 mg/mL) and ranibizumab (125 mg/mL) for 24 hours prior to all experiments, and their effects on gene expressions were determined by RT- PCR. Results After exposure to bevacizumab, more genes in the endothelial cells were up-regulated (KDR, NFATc2) and down-regulated (Pla2g12a, Rac2, HgdC, PRKCG) compared to non-treated controls. After exposure to ranibizumab, fewer genes were up-regulated (PTGS2) and down-regulated (NOS3) compared to controls. In comparison between drugs, more genes were up-regulated (NFATc2 and KDR) and more were down-regulated (Pla2g12a, Pla2g1b, Ppp3r2, Rac2) by bevacizumab than by ranibizumab. In RPE cells, NOS3 and PGF were up-regulated and Pla2g12b was down-regulated after exposure to ranibizumab, while PIK3CG was up-regulated and FIGF was down-regulated after exposure to bevacizumab, but the differences in gene expression were minor between drugs (PIK3CGand PGF were down-regulated more by ranibizumab than by bevacizumab). Conclusions The different gene expressions after exposure to ranibizumab and bevacizumab in endothelial and RPE cells may indicate a somewhat different biological activity of the two compounds.
    Full-text · Article · Sep 2014 · BMC Research Notes
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    • "In the IVAN study, 610 patients were assigned randomly to ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with three consecutive injection series and monthly review. One year after randomisation, the comparison between bevacizumab and ranibizumab was inconclusive and bevacizumab did not meet the NI criteria (bevacizumab minus ranibizumab −1.99 letters, 95% CI −4.04 to 0.06)74. Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous −0.35 letters; 95% CI −2.40 to 1.70). "
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    ABSTRACT: Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. Trial registration number NCT01318941.
    Full-text · Article · Sep 2014 · British Journal of Ophthalmology
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    • "Efficacy was studied in only one of them. Chakravarthy et al. confirmed the functional equivalence of the two drugs (visual acuity) [3]. Retinal thickness at fovea was the only anatomical efficacy criterion analysed, with more favourable results for ranibizumab. "
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    ABSTRACT: Purpose Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. Methods A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed- and random-effects models. Heterogeneity was assessed using the Q statistic and I2. Results Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, −1.80 to 0.66, p = 0.37, I2 = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I2 = 0 %). Conclusions The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events.
    Full-text · Article · Aug 2014 · Albrecht von Graæes Archiv für Ophthalmologie
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