Aflibercept for neovascular age-related macular degeneration

Abstract

Background Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. Objectives To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. Selection criteria We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive. Data collection and analysis We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors independently screened records, abstracted data, and assessed risk of bias of included studies; we resolved discrepancies by discussion or with the help of a third review author when needed. Main results We included two RCTs (total of 2457 participants, 2457 eyes). Trial participants had neovascular AMD with active subfoveal choroidal neovascular lesions. Both trials followed the same protocol and compared aflibercept at various doses versus ranibizumab, but they were carried out in different countries. One trial enrolled participants from the United States and Canada, and the second trial was conducted at 172 sites in Europe, Asia Pacific, Latin America, and the Middle East. The overall quality of the evidence was high, and included trials were at low risk for most bias domains assessed; however, both trials were funded by the manufacturers of aflibercept. For the purposes of analysis, we combined aflibercept groups regardless of dosing and analyzed them as a single group. Visual acuity outcomes were similar between aflibercept and ranibizumab groups...

Editing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation

“…13–15 Although these drugs can reduce vessel leakage and neovascularization, continuous intraocular injections are required, and multiple injections might cause some side effects such as development of geographic atrophy in the eye. 48–51 …”

Macular Edema of Choroidal Origin

“…However, the decrease of leakage of the choroidal new vessels requires multiple injections for a period of 12-24 months and regular follow-up later on. The effectiveness of aflibercept is comparable to ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD (Sarwar et al, 2016) 56 .…”

Calcitriol and Non-Calcemic Vitamin D Analogue, 22-Oxacalcitriol, Attenuate Developmental and Pathological Ocular Angiogenesis Ex Vivo and In Vivo

“…Worldwide 8.7% of blindness results from AMD. nAMD accounts for 10% of AMD cases but ˃80% of cases with poor visual acuity [1][2][3][4]. nAMD and rapid vision loss is driven by pathological choroidal vasculature angiogenesis.…”

“…Ranibizumab (LUCENTIS®), bevacizumab (Avastin®) and aflibercept (Eylea®) are utilised in the treatment of ocular neovascularisation [12]. These anti-VEGF therapies cause vessel regression and improve visual function [4]. Despite representing the standard of care, several treatment limitations exist.…”

“…This places a burden both on patients and clinicians, resulting in inadequate dosing, exemplified by the CATT/IVAN trial, where an average of 4-5 treatments were administered compared to the recommended 7-8 [7]. Secondly, repeat administrations are required: aflibercept has the greatest intravitreal half-life yet injections are required every 2 months [4,14]. Thirdly, anti-VEGF therapies are associated with a severe economic burden, with aflibercept costing approximately €1,000 per injection [15].…”