title: MF59-adjuvanted versus non-adjuvanted influenza vaccines: integrated analysis from a large safety database.
abstract: 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 pandemic influenza vaccines. Safety outcomes were analysed in the overall population and in subjects aged > or =65 years, in all clinical trials and in controlled trials only.
  
  
  RESULTS
  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 [ARR] 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Global Clinical Research & Development, Novartis Vaccines and Diagnostics, 53100 Siena, Italy. michele.pellegrini@novartis.com
authors.forename: Michele
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.forename: Kelly
authors.initials: K
authors.lastname: Lindert
authors.forename: Nicola
authors.initials: N
authors.lastname: Groth
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000009:adverse effects*; D018570:Risk Assessment; D013185:Squalene / Q000009:adverse effects*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene