Five years of safety profile of bevacizumab: an analysis of real-world pharmacovigilance and randomized clinical trials

Abstract

Abstract Objective Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It has a wide range of clinical applications in various cancers and retinal diseases. The drugs entered the Chinese market by a large margin in 2017, and the user population changed to some extent. This study reevaluated the safety of bevacizumab through an analysis of the World Pharmacovigilance database (Food and Drug Administration Open Vigil 2.1) in conjunction with a comprehensive meta-analysis of RCTs. Methods Real-world pharmacovigilance data originating from case reports were mined using Open Vigil and coded at the preferred term (PT) level using the Standardized MedDRA Query. Proportional reporting ratios (PRR) and reporting odds ratios (ROR) were used to detect safety signals. Eligible items were screened by searching PubMed, Wanfang, and Web of Science, and data were extracted for systematic review and meta-analysis using RevMan 5.4 software. Results Analysis of the drug pharmacovigilance database revealed that the most significant PRRs were limb decortication syndrome (PRR = 2926), stomal varices (PRR = 549), anastomotic (PRR = 457) and ureteral fistula (PRR = 406). Most safety signals at the PT level emerged as various types of injuries, toxicities, operational complications, systemic diseases, various reactions at the administration site, hematological and lymphatic disorders, and gastrointestinal disorders. Adverse reactions such as nasal septal perforation (PRR = 47.502), necrotizing fasciitis (PRR = 20.261), and hypertensive encephalopathy (PRR = 18.288) listed as rare in drug specifications should not be ignored with a high signal in the real world. A total of 8 randomized controlled trials (RCTs) were included in the meta-analysis, and the overall risk of adverse reactions following bevacizumab administration was relatively low, indicating a good safety profile (HR = 1.19, 95% CI:0.85 ~ 1.65, p = 0.32). Conclusion The frequent adverse reactions of bevacizumab occurring in the real world are consistent with the data provided in RCTs and drug specifications. However, adverse reactions such as nasal septum perforation, necrotizing fasciitis, hypertensive encephalopathy and so on, listed as rare in drug specifications, may have a high signal of correlation in the real world, which all requires active monitoring and timely adjustment of bevacizumab posology during its clinical use.

Keywords

• Bevacizumab
• Safety
• FDA adverse event reporting system
• Pharmacovigilance
• Meta-analysis