title: Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.
abstract: OBJECTIVE
  The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials.
  
  
  METHODS
  ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used.
  
  
  RESULTS
  The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001).
  
  
  CONCLUSIONS
  Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Biagi
authors.forename: V
authors.initials: V
authors.lastname: Conti
authors.forename: N
authors.initials: N
authors.lastname: Montanaro
authors.forename: M
authors.initials: M
authors.lastname: Melis
authors.forename: E
authors.initials: E
authors.lastname: Buccellato
authors.forename: M
authors.initials: M
authors.lastname: Donati
authors.forename: A
authors.initials: A
authors.lastname: Covezzoli
authors.forename: R
authors.initials: R
authors.lastname: Amato
authors.forename: L
authors.initials: L
authors.lastname: Pazzi
authors.forename: M
authors.initials: M
authors.lastname: Venegoni
authors.forename: A
authors.initials: A
authors.lastname: Vaccheri
authors.forename: D
authors.initials: D
authors.lastname: Motola
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D052157:Aptamers, Nucleotide / Q000009:adverse effects*; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy; D008297:Male; D000069579:Ranibizumab; D014944:World Health Organization
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; C495058:pegaptanib; D000068258:Bevacizumab; D000069579:Ranibizumab