Global Vaccine Safety

Statement on narcolepsy and vaccination

21 April 2011

Since August 2010, following widespread use of vaccines against influenza (H1N1) 2009, cases of narcolepsy, especially in children and adolescents, have been reported. Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. The rates reported from Sweden, Finland and Iceland have been notably higher than those from other countries. Swedish and Finnish authorities have presented preliminary statements on their investigations in the first quarter of 2011.

On 1 February 2011, the National Institute for Health and Welfare of Finland issued a preliminary statement following an investigation into the cases of narcolepsy in Finland1 . A systematic retrospective registry-based review was conducted of all new narcolepsy cases diagnosed during 2006-2010. Cases from 2009-2010, who were born in 1990 or later, were reviewed using newly developed Brighton collaboration criteria for the disease. During 2009-2010 they found that the risk of narcolepsy among people aged 4-19 years old who had received pandemic influenza vaccine was nine times higher than that among those who had not been vaccinated. This corresponds to a risk of about 1 case of narcolepsy per 12,000 vaccinated in this age group. No increased risk has been seen in younger or older age groups.

The Swedish Medical Products Agency issued a preliminary report on 28 March 2011 following an investigation on pandemic influenza vaccination using data drawn from regional vaccination registries of four Swedish counties2. Covering a population of 5.3 million, the risk of narcolepsy was compared in vaccinated and unvaccinated individuals from October 2009 to December 2010. The Agency reported that the relative risk of narcolepsy was four times higher in vaccinated children and adolescents (born from 1990) compared to unvaccinated individuals. The relative risk estimate translates into an absolute risk of about 3 cases of narcolepsy in 100,000 vaccinated adolescents/children. The incidence rates for narcolepsy in adults irrespective of vaccination status were similar to historical national registry- based rates during the years before the pandemic period (i.e. about 1/100,000).

The only pandemic influenza vaccine used in Finland and Sweden was Pandemrix, an adjuvanted influenza A (H1N1) 2009 monovalent vaccine manufactured by GlaxoSmithKline.

Narcolepsy is a condition that has a strong genetic linkage, being almost uniquely seen in persons who have the (HLA) DQB1*0602 genotype. Of the cases of narcolepsy tested so far in Finland (n=29), diagnosed during 2009-2010, all have that genotype. The National Institute for Health and Welfare of Finland considers it probable that the Pandemrix vaccine was a contributing factor to this observed increase, and has called for further investigation of other co-factors that may be associated with the increased risk. They consider it most likely that the vaccine increased the risk of narcolepsy in a joint effect in those genetically disposed with some other, still unknown, genetic and/or environmental factors. The final report from the Finnish National Narcolepsy Task Force is expected by 31 August 2011.

The Swedish Medical Products Agency recognizes that further work is needed with respect to the findings in their preliminary report - particularly with regards to the verification of the diagnoses of the cases ascertained from the county health care databases. Also, in the report there is no assessment as to whether publicity about the purported association influenced rates in vaccinated compared to unvaccinated persons. Further investigations include a review by the European Medicines Agency (EMA) on the benefit-risk balance of Pandemrix, which is expected by July 2011. At their meeting in April 2011, the EMA Committee for Medicinal Products for Human Use (CHMP) agreed an interim recommendation for prescribers to take into account preliminary results from epidemiological studies on Pandemrix and narcolepsy, and to perform an individual benefit-risk assessment when considering the use of Pandemrix in children and adolescents3. Results from an epidemiological study of narcolepsy and pandemic vaccines in nine EU States by the VAESCO project are expected by June 20114.

WHO's Global Advisory Committee on Vaccine Safety (GACVS) reviewed the available data from Finland on 4 February 2011 and the new data from Sweden on 18 April 2011. GACVS agrees that further investigation is warranted concerning narcolepsy and vaccination against influenza (H1N1) 2009 with Pandemrix and other pandemic H1N1 vaccines. An increased risk of narcolepsy has not been observed in association with the use of any vaccines whether against influenza or other diseases in the past. Even at this stage, it does not appear that narcolepsy following vaccination against pandemic influenza is a general worldwide phenomenon, as no excess of narcolepsy has been reported from several other European states where Pandemrix was used, or from Canada where a pandemic vaccine similar to pandemrix was used. This complicates interpretation of the findings in Finland and Sweden. It seems likely that some as yet unidentified additional factor was operating in Sweden and Finland. The findings from the VAESCO project and further investigations in Finland and Sweden, may help clarify the determinants of any increased risk of narcolepsy, which currently appears to be restricted to the months following vaccination and by age group and country.

GACVS will continue to monitor the situation closely and updates will be provided as further information becomes available and is assessed.

1. Statement from the National Institute for Health and Welfare of Finland of 1 February 2011

2. Statement from the Swedish Medical Products Agency of 28 March 2011

3. Recommended interim measures for Pandemrix from the European Medicines Agency 15 April 2011

4. ECDC – VAESCO investigation into narcolepsy 2 February 2011