Martin K Schmid1, Lucas M Bachmann2, Livia Fäs2, Alfons G Kessels3, Oliver M Job1, Michael A Thiel1. 1. Eye Clinic, Cantonal Hospital of Lucerne, Lucerne, Switzerland. 2. Medignition Inc. Research Consultants, Zug, Switzerland. 3. Department of Clinical Epidemiology and Medical, Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
Abstract
TOPIC: To quantify the gain in visual acuity and serious side effects of ranibizumab, bevacizumab and aflibercept in age-related macular degeneration (AMD). CLINICAL RELEVANCE: There is an ongoing debate about the optimal treatment of AMD with these three antivascular endothelial growth factor (anti-VEGF) treatments. METHODS: Network meta-analyses. (Pre)Medline, EMBASE, SCOPUS, Cochrane Library (until April 2013), Science Citation Index and reference lists were searched for placebo-controlled randomised trials or head-to-head comparisons. Outcomes were 1-year follow-up data of visual acuity (letters gained) and serious (vascular death, any death, stroke, myocardial infarction, transient ischaemic attack) and thrombotic events. Two investigators independently assessed eligibility and quality of included studies and extracted data. RESULTS: 11 trials (enrolling 8341 patients) assessing five active treatments were included. Compared with placebo, all anti-VEGF treatments had a significantly higher percentage of letters gained: ranibizumab 0.3 mg 2.39% (95% CI 1.59 to 3.19; p<0.001), ranibizumab 0.5 mg 3.56% (95% CI 2.58 to 4.13; p<0.001), bevacizumab 1.25 mg 2.14% (95% CI 0.47 to 3.82; p=0.012), aflibercept 0.5 mg 2.91% (95% CI 0.99 to 4.82; p=0.003) and aflibercept 2 mg 3.44% (95% CI 1.73 to 5.14; p<0.001). Compared with placebo, serious side effects were higher in all other treatments: ranibizumab 0.3 mg 4.41% (95% CI 3.42 to 5.40; p<0.001), ranibizumab 0.5 mg 5.33% (95% CI 4.37 to 6.30; p<0.001), bevacizumab 1.25 mg 5.58% (95% CI 3.567 to 7.60; p<0.001), aflibercept 0.5 mg 5.65% (95% CI (3.28 to 8.02; p<0.001) and aflibercept 2 mg 5.29% (95% CI 3.18 to 7.39; p<0.001). Compared with placebo, systemic thrombotic events also occurred more often in all other treatments. CONCLUSIONS: The study revealed only a modest superiority of aflibercept 2 mg and ranibizumab 0.5 mg over other formulations and dosages. 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.
TOPIC: To quantify the gain in visual acuity and serious side effects of ranibizumab, bevacizumab and aflibercept in age-related macular degeneration (AMD). CLINICAL RELEVANCE: There is an ongoing debate about the optimal treatment of AMD with these three antivascular endothelial growth factor (anti-VEGF) treatments. METHODS: Network meta-analyses. (Pre)Medline, EMBASE, SCOPUS, Cochrane Library (until April 2013), Science Citation Index and reference lists were searched for placebo-controlled randomised trials or head-to-head comparisons. Outcomes were 1-year follow-up data of visual acuity (letters gained) and serious (vascular death, any death, stroke, myocardial infarction, transient ischaemic attack) and thrombotic events. Two investigators independently assessed eligibility and quality of included studies and extracted data. RESULTS: 11 trials (enrolling 8341 patients) assessing five active treatments were included. Compared with placebo, all anti-VEGF treatments had a significantly higher percentage of letters gained: ranibizumab 0.3 mg 2.39% (95% CI 1.59 to 3.19; p<0.001), ranibizumab 0.5 mg 3.56% (95% CI 2.58 to 4.13; p<0.001), bevacizumab 1.25 mg 2.14% (95% CI 0.47 to 3.82; p=0.012), aflibercept 0.5 mg 2.91% (95% CI 0.99 to 4.82; p=0.003) and aflibercept 2 mg 3.44% (95% CI 1.73 to 5.14; p<0.001). Compared with placebo, serious side effects were higher in all other treatments: ranibizumab 0.3 mg 4.41% (95% CI 3.42 to 5.40; p<0.001), ranibizumab 0.5 mg 5.33% (95% CI 4.37 to 6.30; p<0.001), bevacizumab 1.25 mg 5.58% (95% CI 3.567 to 7.60; p<0.001), aflibercept 0.5 mg 5.65% (95% CI (3.28 to 8.02; p<0.001) and aflibercept 2 mg 5.29% (95% CI 3.18 to 7.39; p<0.001). Compared with placebo, systemic thrombotic events also occurred more often in all other treatments. CONCLUSIONS: The study revealed only a modest superiority of aflibercept 2 mg and ranibizumab 0.5 mg over other formulations and dosages. 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.