Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

BACKGROUND: Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. METHODS: This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. RESULTS: A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. CONCLUSION: In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01985997.