Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

ABSTRACT

PURPOSE: 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.