Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study.
TL;DR: In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, and at month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens.
About: This article is published in Ophthalmology.The article was published on 2011-05-01. It has received 376 citations till now. The article focuses on the topics: Ranibizumab & Population.
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TL;DR: Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizuab administered monthly, although the comparison between bevacizumAB as needed and monthly bevicizumabs was inconclusive.
Abstract: Background Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. Methods In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Results Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. Conclusions At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).
2,425 citations
TL;DR: It is demonstrated that aflibercept is an effective treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring.
1,894 citations
TL;DR: VEGF Trap is differentiated in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGf-B and PlGF, a novel type of soluble decoy receptor with substantially higher affinity than conventional soluble V EGF receptors.
Abstract: Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.
858 citations
TL;DR: All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks, and the 2q8 a flibercept group was similar to ranibIZumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections.
688 citations
Cites methods from "Efficacy and safety of monthly vers..."
...To reduce the treatment burden and still conform to a structured regimen, treatment intervals were expanded in studies such as the Phase IIIB, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Patients with AMDRelated Subfoveal Choroidal Neovascularization (CNV), with or without Classic CNV(PIER), and the Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration (EXCITE).(7,8) However, the visual acuity benefit of ranibizumab therapy was reduced markedly when treatment intervals were increased up to 3 months....
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TL;DR: The discovery of V EGFA, the successes and challenges in the development of VEGFA inhibitors and the impact of these agents on the treatment of cancers and ophthalmic diseases are discussed.
Abstract: The targeting of vascular endothelial growth factor A (VEGFA), a crucial regulator of both normal and pathological angiogenesis, has revealed innovative therapeutic approaches in oncology and ophthalmology. The first VEGFA inhibitor, bevacizumab, was approved by the US Food and Drug Administration in 2004 for the first-line treatment of metastatic colorectal cancer, and the first VEGFA inhibitors in ophthalmology, pegaptanib and ranibizumab, were approved in 2004 and 2006, respectively. To mark this tenth anniversary of anti-VEGFA therapy, we discuss the discovery of VEGFA, the successes and challenges in the development of VEGFA inhibitors and the impact of these agents on the treatment of cancers and ophthalmic diseases.
672 citations
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TL;DR: Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration.
Abstract: Background Ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — has been evaluated for the treatment of neovascular age-related macular degeneration. Methods In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. Results We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab. Conclusions Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836.)
5,004 citations
TL;DR: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events and treatment improved visual acuity on average at 1 year.
Abstract: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). Conclusions Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials. gov number, NCT00061594.)
3,207 citations
TL;DR: A 2-year phase III trial designated ANCHOR as discussed by the authors compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV.
1,259 citations
TL;DR: The final antibody has improved affinity for several VEGF variants as compared with the parental antibody; however, some contact residues on V EGF differ in their contribution to the energetics of Fab binding.
1,241 citations
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