Aflibercept for Age-Related Macular Degeneration and Central Retinal Vein Occlusion

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPONI, A; ROMANO, M

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Age-Related Macular Degeneration (AMD) is one of the most common causes ofblindness in subjects over 50 years of age. It affects 4% of subjects over 55 years old andits incidence increases with age, so that over 75 years old its prevalence is 8%. Its wetform (neovascularization) represents 10% of all the cases, although it accounts for 90% ofsevere vision loss. Laser photocoagulation therapy is useful only when the fovea is notinvolved (20% of the cases). For the remaining 80%, first line treatment includesangiogenesis inhibitors such as ranibizumab. There are other drugs from the same classsuch as bevacizumab, and aflibercept which are considered potential alternatives.Venous retinal occlusion is the second most common cause of retinal diseases. It isestimated that prevalence of retinal venous occlusion is 1-2% in subjects over 40 years oldand it would affect about 16 million people worldwide. Macular edema is the most commoncause of vision loss therefore angiogenesis inhibitors are proposed as potentialtreatments.TechnologyAflibercept is a potent and specific blocker of human 1 and 2 VEGF receptors. Anti-VEGFtreatment could prevent the inappropriate growth of new vessels in the retina anddecrease vascular patency thus reducing macular edema. In 2011, the FDA approved it forneovascular AMD (wet type) treatment. The recommended dose is 2 mg (0.05 mL) and itis administered through intravitreal injection every 4 weeks during the first 3 months andlater every 8 weeks. EMA approved its use for wet AMD treatment in adult patients inNovember 2012.PurposeTo assess the available evidence on the efficacy, safety and coverage policy relatedaspects on the use of aflibercept in patients with age-related macular degeneration andcentral retinal artery thrombosis.MethodsA bibliographic search was carried out on the main literature databases: DARE, NHS EED,on Internet general search engines, in health technology evaluation agencies and healthsponsors. Priority was given to the inclusion of systematic reviews; controlled, randomizedclinical trials (RCTs); health technology assessments and economic evaluations; clinicalpractice guidelines and coverage policies of other health systems.ResultsAge-Related Macular DegenerationTwo randomized clinical trials (RCTs), a clinical practice guideline (CPG) and twocoverage policies were found.The two RCTs were multicenter, double blind and had a non-inferiority design: VIEW 1(N=1,217) and VIEW 2 (N=1,240). The mean age of the patients enrolled was 76 yearsold. Both studies included patients with wet AMD who were randomized to intravitrealaflibercept 0.5 mg monthly, 2 mg monthly, or 2 mg every 2 months, and who had beenpretreated with a monthly loading dose of Lucentis® (ranibizumab) for 3 months orintravitreal treatment with 0.5 mg monthly for 12 months (standard treatment for thiscondition). The primary outcome for both studies was the number of patients who retainedvision at 12 months, defined as vision loss of less than 15 letters measured in the EarlyTreatment Diabetic Retinopathy Study Chart. In Study VIEW 1, aflibercept 0.5 mg monthly,2 mg monthly and 2 mg every 2 months showed no inferiority compared to ranibizumab inthe number of patients who retained vision (95.9; 95.1 and 95.1 versus 94.4%,respectively. P was not reported). Similar results were described for VIEW 2 betweenaflibercept and ranibizumab (96.3; 95.6 and 95.6 versus 94.4%, respectively. P was notreported). Also all the aflibercept schemes studied resulted in similar improvements in eyefundoscopy. The incidence of adverse effects was similar for both treated groups. Duringthe second year of treatment, effectiveness continued.Central Retinal Vein OcclusionNo clinical trials, clinical practice guidelines or coverage policies for aflibercept were foundfor this indication.The CPG published by the U.S. agency Blue Cross Blue Shield from North Caroline statesthat aflibercept intravitreal injection might be useful for wet AMD treatment. It is notrecommended for macular edema due to the occlusion of the central retinal artery or itsbranches.Medicare, the U.S. agency, intravitreal aflibercept for wet AMD treatment.ConclusionsThe evidence found for wet AMD was of very high methodological quality. All theaflibercept doses and schemes evaluated were as effective as ranibizumab (standardtreatment) for the treatment of wet AMD patients.No evidence was found supporting aflibercept in patients with central retinal veinocclusion.