MF59-adjuvanted versus non-adjuvanted influenza vaccines: Integrated analysis from a large safety database

Background: Adding adjuvants such as MF59 (R) to influenza vaccines can enhance the immune response. This analysis evaluated the safety profile of MF59-adjuvanted [(+)MF59] compared with non adjuvanted [(-)MF59] vaccines in a large clinical database. Methods: Safety data were pooled from 64 clinical trials involving (+)MF59 seasonal and pandem ic influenza vaccines. Safety outcomes were analysed in the overall population and in subjects aged >= 65 years, in all clinical trials and in controlled trials only. Findings: Data from 20,447 (+)MF59 and 7526 (-)MF59 subjects were analysed. Overall, (+)MF59 subjects had lower risks than (-)MF59 subjects of experiencing any unsolicited adverse event (AE) (26.8% vs 39.2%; adjusted risk ratio JARRI 0.65; 95% CI 0.60-0.70), cardiovascular AEs (1.9% vs 5.6%: ARR 0.44: 95% CI 0.35-0.55), new onset chronic diseases (1.3% vs 1.9%; ARR 0.71: 95% CI 0.57-0.87) and death (0.8% vs 1.2%: ARR 0.67; 95% CI 0.51-0.87). Few AEs of potential autoimmune origin were reported: 0.71 and 0.67 per 1000 with (+)MF59 and (-)MF59, respectively. As expected, (+)MF59 subjects had a higher risk of solicited local or systemic reactions within 3 days of vaccination (58.5% vs 46.9%, weighted RR 1.34; 95% CI 1.28-1.40). Safety outcomes were consistent between total and elderly populations, and between all trials and controlled trials, although statistical significance was lost for some of the outcomes in the subgroups. Interpretation: This large-scale analysis supports the good safety profile of (+)MF59 seasonal and pandemic influenza vaccines and suggests a clinical benefit over (-)MF59 influenza vaccines. (C) 2009 Elsevier Ltd. All rights reserved.