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.; CIAPPONI, 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 of blindness in subjects over 50 years of age. It affects 4% of subjects over 55 years old and its incidence increases with age, so that over 75 years old its prevalence is 8%. Its wet form (neovascularization) represents 10% of all the cases, although it accounts for 90% of severe vision loss. Laser photocoagulation therapy is useful only when the fovea is not involved (20% of the cases). For the remaining 80%, first line treatment includes angiogenesis inhibitors such as ranibizumab. There are other drugs from the same class such as bevacizumab, and aflibercept which are considered potential alternatives. Venous retinal occlusion is the second most common cause of retinal diseases. It is estimated that prevalence of retinal venous occlusion is 1-2% in subjects over 40 years old and it would affect about 16 million people worldwide. Macular edema is the most common cause of vision loss therefore angiogenesis inhibitors are proposed as potential treatments. Technology Aflibercept is a potent and specific blocker of human 1 and 2 VEGF receptors. Anti-VEGF treatment could prevent the inappropriate growth of new vessels in the retina and decrease vascular patency thus reducing macular edema. In 2011, the FDA approved it for neovascular AMD (wet type) treatment. The recommended dose is 2 mg (0.05 mL) and it is administered through intravitreal injection every 4 weeks during the first 3 months and later every 8 weeks. EMA approved its use for wet AMD treatment in adult patients in November 2012. Purpose To assess the available evidence on the efficacy, safety and coverage policy related aspects on the use of aflibercept in patients with age-related macular degeneration and central retinal artery thrombosis. Methods A bibliographic search was carried out on the main literature databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems. Results Age-Related Macular Degeneration Two randomized clinical trials (RCTs), a clinical practice guideline (CPG) and two coverage 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 years old. Both studies included patients with wet AMD who were randomized to intravitreal aflibercept 0.5 mg monthly, 2 mg monthly, or 2 mg every 2 months, and who had been pretreated with a monthly loading dose of Lucentis® (ranibizumab) for 3 months or intravitreal treatment with 0.5 mg monthly for 12 months (standard treatment for this condition). The primary outcome for both studies was the number of patients who retained vision at 12 months, defined as vision loss of less than 15 letters measured in the Early Treatment 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 in the 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 between aflibercept and ranibizumab (96.3; 95.6 and 95.6 versus 94.4%, respectively. P was not reported). Also all the aflibercept schemes studied resulted in similar improvements in eye fundoscopy. The incidence of adverse effects was similar for both treated groups. During the second year of treatment, effectiveness continued. Central Retinal Vein Occlusion No clinical trials, clinical practice guidelines or coverage policies for aflibercept were found for this indication. The CPG published by the U.S. agency Blue Cross Blue Shield from North Caroline states that aflibercept intravitreal injection might be useful for wet AMD treatment. It is not recommended for macular edema due to the occlusion of the central retinal artery or its branches. Medicare, the U.S. agency, intravitreal aflibercept for wet AMD treatment. Conclusions The evidence found for wet AMD was of very high methodological quality. All the aflibercept doses and schemes evaluated were as effective as ranibizumab (standard treatment) for the treatment of wet AMD patients. No evidence was found supporting aflibercept in patients with central retinal vein occlusion.