Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration

• Published in: Cochrane database of systematic reviews 2014-09, Vol.9 (9), p.CD011230-CD011230
• Main Authors: Moja, Lorenzo, Lucenteforte, Ersilia, Kwag, Koren H, Bertele, Vittorio, Campomori, Annalisa, Chakravarthy, Usha, D'Amico, Roberto, Dickersin, Kay, Kodjikian, Laurent, Lindsley, Kristina, Loke, Yoon, Maguire, Maureen, Martin, Daniel F, Mugelli, Alessandro, Mühlbauer, Bernd, Püntmann, Isabel, Reeves, Barnaby, Rogers, Chris, Schmucker, Christine, Subramanian, Manju L, Virgili, Gianni
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Bevacizumab; Humans; Intravitreal Injections; Macular Degeneration - drug therapy; Macular Degeneration - mortality; Middle Aged; Ranibizumab; Vascular Endothelial Growth Factor A - antagonists & inhibitors
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD011230.pub2

Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD. To assess the systemic safety of intravitreal bevacizumab (brand name Avastin®; Genentech/Roche) compared with intravitreal ranibizumab (brand name Lucentis®; Novartis/Genentech) in people with neovascular AMD. Primary outcomes were death and All serious systemic adverse events (All SSAEs), the latter as a composite outcome in accordance with the International Conference on Harmonisation Good Clinical Practice. Secondary outcomes examined specific SSAEs: fatal and non-fatal myocardial infarctions, strokes, arteriothrombotic events, serious infections, and events grouped in some Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC). We assessed the safety at the longest available follow-up to a maximum of two years. We searched CENTRAL, MEDLINE, EMBASE and other online databases up to 27 March 2014. We also searched abstracts and clinical study presentations at meetings, trial registries, and contacted authors of included studies when we had questions. Randomised controlled trials (RCTs) directly comparing intravitreal bevacizumab (1.25 mg) and ranibizumab (0.5 mg) in people with neovascular AMD, regardless of publication status, drug dose, treatment regimen, or follow-up length, and whether the SSAEs of interest were reported in the trial report. Two authors independently selected studies and assessed the risk of bias for each study. Three authors independently extracted data.We conducted random-effects meta-analyses for the primary and secondary outcomes. We planned a pre-specified analysis to explore deaths and All SSAEs at the one-year follow-up. We included data from nine studies (3665 participants), including six published (2745 participants) and three unpublished (920 participants) RCTs, none supported by industry. Three studies excluded participants at high ca