title: Explorations of clinical trials and pharmacovigilance databases of MF59®-adjuvanted influenza vaccines for associated cases of narcolepsy.
abstract: BACKGROUND
  A potential association between the new onset of narcolepsy accompanied by cataplexy - a putative autoimmune disorder, and vaccination with an AS03-adjuvanted A(H1N1) pandemic influenza vaccine is under investigation. We sought cases of narcolepsy from the pharmacovigilance database of a pandemic vaccine adjuvanted with another emulsion adjuvant, MF59(®), and a pooled clinical trials database of MF59-adjuvanted and non-adjuvanted influenza vaccine recipients.
  
  
  METHODS
  Using 6 narrowly restrictive and 24 broad sleep disturbance-related MedDRA preferred search terms (PT), we analysed spontaneous adverse events (AEs) reports received through July 31, 2010 and adjudicated suspected cases with onset 1 week-3 months after vaccination, against standardized clinical criteria defining narcolepsy. A pooled clinical trials database of 115 trials comprising 79,004 subjects receiving various MF59-adjuvanted and non-adjuvanted influenza vaccines in controlled and uncontrolled trials was analysed for cases with a narrow PT that had onset 1 week after vaccination.
  
  
  RESULTS
  Five thousand three hundred and five spontaneous AE reports were received from an estimated 23.26 million MF59-adjuvanted pandemic vaccine doses that had been administered. No case meeting the clinical definition of narcolepsy was discovered. In the pooled database of controlled clinical trials, no cases were discovered using the narrow PT, and rates and adjusted odds ratio for broad search terms for all temporal windows showed no significant difference between subjects receiving MF59-adjuvanted or non-adjuvanted vaccine.
  
  
  CONCLUSIONS
  No case of narcolepsy and no evidence of an increased risk of sleep-related AEs were discovered in recipients of MF59-adjuvanted A(H1N1) pandemic and other MF59-adjuvanted influenza vaccine.
authors.affiliation: Novartis Vaccines and Diagnostics Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, USA. theodore.tsai@novartis.com
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Tsai
authors.forename: Antonio
authors.initials: A
authors.lastname: Crucitti
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Nacci
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
authors.forename: John
authors.initials: J
authors.lastname: Ferguson
authors.forename: Ralf
authors.initials: R
authors.lastname: Clemens
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D009290:Narcolepsy / Q000139:chemically induced* / Q000453:epidemiology* / Q000209:etiology; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene