Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec

Abstract

Main Outcome Measures: Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method. Context: An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe. Objective: To assess narcolepsy risk following administration of a similar vaccine in Quebec. Design: Retrospective population-based study. Setting: Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre. Population: Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry. Conclusions: Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out. Results: A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons ,20 years old and for cataplexy cases.