title: Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines.
abstract: BACKGROUND
  A recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection.
  
  
  METHODS
  The original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6-8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1-Rate Ratio)×100.
  
  
  RESULTS
  31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6-27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3-55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5-12.8%).
  
  
  CONCLUSIONS
  Compared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults.
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: carlos.diazgranados@sanofipasteur.com.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: DiazGranados
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA.
authors.forename: Corwin A
authors.initials: CA
authors.lastname: Robertson
authors.affiliation: Vanderbilt University Medical Center, A2200 MCN 1161 21st Ave S, Nashville, TN 37212, USA.
authors.forename: H Keipp
authors.initials: HK
authors.lastname: Talbot
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Landolfi
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dunning
authors.affiliation: Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006760:Hospitalization; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Aged; Aged, 80 and over; Clinical trial, phase III; Influenza vaccines, human; Vaccines, inactivated