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      Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration

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          Abstract

          Background/aims

          Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela.

          Methods

          Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011.

          Results

          2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity.

          Conclusions

          In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time.

          Trial registration number

          NCT01447043.

          Related collections

          Most cited references12

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          Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial.

          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. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study.

            To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Twelve-month, phase III, multicenter, open-label, single-arm study. A total of 513 ranibizumab-naïve SUSTAIN patients. Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe. Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed. A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity [VA], vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 μm from baseline to month 3 and -91.5 μm from baseline to month 12. The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies; individualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with individualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study.

              To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). 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, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly, -105.6 μm in 0.5 mg quarterly, and -105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Br J Ophthalmol
                Br J Ophthalmol
                bjophthalmol
                bjo
                The British Journal of Ophthalmology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0007-1161
                1468-2079
                February 2015
                5 September 2014
                : 99
                : 2
                : 220-226
                Affiliations
                [1 ]Department of Ophthalmology, University of Bonn , Bonn, Germany
                [2 ]Department of Ophthalmology, Hôpital Lariboisière, AP-HP, Université Paris 7—Sorbonne Paris Cité , France
                [3 ]Department of Ophthalmology, Institute of Eye Surgery , Waterford, Ireland
                [4 ]Department of Ophthalmology and Vision Sciences, University of Toronto, and St Michael's Hospital , Toronto, Canada
                [5 ]Department of Biomedical and Clinical Science Luigi Sacco, Luigi Sacco Hospital, University of Milan , Milan, Italy
                [6 ]Centro de Cirugia Oftalmologica , Caracas, Venezuela
                [7 ]Department of Ophthalmology, Radboud University Nijmegen Medical Centre , Nijmegen, The Netherlands
                [8 ]NIHR Biomedical Centre for Research in Ophthalmology, Moorfields Eye Hospital , London, UK
                [9 ]Bayer HealthCare Pharmaceuticals , Berlin, Germany
                [10 ]Bayer HealthCare Pharmaceuticals , Montville, New Jersey, USA
                [11 ]King's College Hospital , London, UK
                Author notes
                [Correspondence to ] Sobha Sivaprasad, King's College Hospital, Denmark Hill, London SE5 9RS, UK; senswathi@ 123456aol.com
                Article
                bjophthalmol-2014-305327
                10.1136/bjophthalmol-2014-305327
                4316940
                25193672
                59e4ff54-b698-4d71-8855-3b54ee634bc7
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 31 March 2014
                : 9 July 2014
                : 16 August 2014
                Categories
                1506
                1507
                Clinical Science
                Custom metadata
                unlocked
                editors-choice

                Ophthalmology & Optometry
                degeneration,macula,treatment medical
                Ophthalmology & Optometry
                degeneration, macula, treatment medical

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