Aflibercept in Wet AMD Beyond the First Year of Treatment
Aflibercept in Wet AMD Beyond the First Year of Treatment
This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.
Neovascular or wet age-related macular degeneration (AMD) accounts for 10–15% of all cases of AMD. In the UK alone it was estimated that there were 263 000 cases of wet AMD in 2007–2009, with an annual incidence of 39 700 new cases. The prevalence of wet AMD is rising, and is expected to increase by one-third by 2020. Without treatment, wet AMD leads to severe central vision loss.
Wet AMD is typically characterised by the growth of abnormal blood vessels from the choroid into the space under the retinal pigment epithelium or the neurosensory retina. These new vessels can leak serous fluid and/or blood, leading to a reduction in central vision. Clinical features of active wet AMD can include one or more of the following: sub-retinal fluid, intra-retinal fluid, sub-retinal haemorrhage, retinal pigment epithelial detachment, and intra-retinal exudates within the macula.
Vascular endothelial growth factor (VEGF) plays a key role in intraocular neovascularisation in a number of conditions; it not only promotes angiogenesis (by stimulating vascular endothelial cell proliferation and migration) but also increases vascular permeability. VEGF-A, acting via the VEGF receptor 2, is thought to be the main stimulator of angiogenesis and vascular permeability in wet AMD.
Anti-VEGF agents such as aflibercept (EYLEA
; aflibercept solution for injection, Regeneron Pharmaceuticals, Inc, Tarrytown, NY and Bayer HealthCare Pharmaceuticals, Berlin, Germany) have become the mainstay of treatment for wet AMD. Aflibercept is a fusion protein, combining the key binding domains of VEGF receptors 1 and 2 and the Fc portion of immunoglobulin G. Dosing for aflibercept in wet AMD is initiated with one 2 mg injection per month for three consecutive doses followed by one 2 mg injection every 2 months during the first year. Monitoring between injections is not required. After 1 year of treatment, the treatment interval may be extended based on visual and anatomical outcomes ( Table 1). In this event, the schedule of monitoring visits is determined by the treating physician and may be more frequent than the schedule of injections.
Aflibercept was licensed in Europe for the treatment of wet AMD in November 2012, and approved by the National Institute for Health and Care Excellence (NICE) in July 2013. Given the 90-day commissioning rule, all ophthalmology units in the UK would already be expected (as of November 2014) to have some patients who have completed 1 year of treatment with aflibercept. A national roundtable was therefore convened to discuss UK experience with aflibercept to date, and to use this experience, together with expert opinion, to develop recommendations on the practical application of aflibercept in wet AMD after Year 1. In particular, the discussion was based around maintaining the visual acuity (VA) gains from Year 1 and reducing treatment burden where possible. This paper will review the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) study with aflibercept in wet AMD, and the recommendations developed by the panel.
Abstract and Introduction
Abstract
This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.
Introduction
Neovascular or wet age-related macular degeneration (AMD) accounts for 10–15% of all cases of AMD. In the UK alone it was estimated that there were 263 000 cases of wet AMD in 2007–2009, with an annual incidence of 39 700 new cases. The prevalence of wet AMD is rising, and is expected to increase by one-third by 2020. Without treatment, wet AMD leads to severe central vision loss.
Wet AMD is typically characterised by the growth of abnormal blood vessels from the choroid into the space under the retinal pigment epithelium or the neurosensory retina. These new vessels can leak serous fluid and/or blood, leading to a reduction in central vision. Clinical features of active wet AMD can include one or more of the following: sub-retinal fluid, intra-retinal fluid, sub-retinal haemorrhage, retinal pigment epithelial detachment, and intra-retinal exudates within the macula.
Vascular endothelial growth factor (VEGF) plays a key role in intraocular neovascularisation in a number of conditions; it not only promotes angiogenesis (by stimulating vascular endothelial cell proliferation and migration) but also increases vascular permeability. VEGF-A, acting via the VEGF receptor 2, is thought to be the main stimulator of angiogenesis and vascular permeability in wet AMD.
Anti-VEGF agents such as aflibercept (EYLEA
; aflibercept solution for injection, Regeneron Pharmaceuticals, Inc, Tarrytown, NY and Bayer HealthCare Pharmaceuticals, Berlin, Germany) have become the mainstay of treatment for wet AMD. Aflibercept is a fusion protein, combining the key binding domains of VEGF receptors 1 and 2 and the Fc portion of immunoglobulin G. Dosing for aflibercept in wet AMD is initiated with one 2 mg injection per month for three consecutive doses followed by one 2 mg injection every 2 months during the first year. Monitoring between injections is not required. After 1 year of treatment, the treatment interval may be extended based on visual and anatomical outcomes ( Table 1). In this event, the schedule of monitoring visits is determined by the treating physician and may be more frequent than the schedule of injections.
Aflibercept was licensed in Europe for the treatment of wet AMD in November 2012, and approved by the National Institute for Health and Care Excellence (NICE) in July 2013. Given the 90-day commissioning rule, all ophthalmology units in the UK would already be expected (as of November 2014) to have some patients who have completed 1 year of treatment with aflibercept. A national roundtable was therefore convened to discuss UK experience with aflibercept to date, and to use this experience, together with expert opinion, to develop recommendations on the practical application of aflibercept in wet AMD after Year 1. In particular, the discussion was based around maintaining the visual acuity (VA) gains from Year 1 and reducing treatment burden where possible. This paper will review the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) study with aflibercept in wet AMD, and the recommendations developed by the panel.