Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines - Multi-country assessment.
BACKGROUND
In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines.


METHODS
We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009.


RESULTS
No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03.


CONCLUSIONS
Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study.
['Weibel|Daniel|D|', 'Sturkenboom|Miriam|M|', 'Black|Steven|S|', 'de Ridder|Maria|M|', 'Dodd|Caitlin|C|', 'Bonhoeffer|Jan|J|', 'Vanrolleghem|Ann|A|', 'van der Maas|Nicoline|N|', 'Lammers|Gert Jan|GJ|', 'Overeem|Sebastiaan|S|', 'Gentile|Angela|A|', 'Giglio|Norberto|N|', 'Castellano|Vanesa|V|', 'Kwong|Jeffrey C|JC|', 'Murray|Brian J|BJ|', 'Cauch-Dudek|Karen|K|', 'Juhasz|Diana|D|', 'Campitelli|Michael|M|', 'Datta|Alexandre N|AN|', 'Kallweit|Ulf|U|', 'Huang|Wan-Ting|WT|', 'Huang|Yu-Shu|YS|', 'Hsu|Chung-Yao|CY|', 'Chen|Hsi-Chung|HC|', 'Giner-Soriano|Maria|M|', 'Morros|Rosa|R|', 'Gaig|Carles|C|', 'Tió|Ester|E|', 'Perez-Vilar|Silvia|S|', 'Diez-Domingo|Javier|J|', 'Puertas|Francisco Javier|FJ|', 'Svenson|Lawrence W|LW|', 'Mahmud|Salaheddin M|SM|', 'Carleton|Bruce|B|', 'Naus|Monika|M|', 'Arnheim-Dahlström|Lisen|L|', 'Pedersen|Lars|L|', 'DeStefano|Frank|F|', 'Shimabukuro|Tom T|TT|']
D000276:Adjuvants, Immunologic D016022:Case-Control Studies D006801:Humans D053118:Influenza A Virus, H1N1 Subtype D007252:Influenza Vaccines D007251:Influenza, Human D009290:Narcolepsy D012189:Retrospective Studies D014611:Vaccination
Narcolepsy Adjuvant Pandemic H1N1 influenza AS03 MF59