1 Sep 2011
An association between Pandemrix and narcolepsy among children and adolescents in Finland is confirmed
In its final report, the National Narcolepsy Task Force confirms the tentative conclusion published in its Interim Report last January that the Pandemrix vaccine used in the winter of 2009–2010 contributed to the increased incidence of narcolepsy observed among 4–19-year-olds in Finland. According to the report, the increased risk associated with vaccination amounted to six cases of narcolepsy per 100 000 persons vaccinated in the 4–19 age group during the eight months following vaccination. This was 12.7 times the risk of a person in the same age group who had not been vaccinated. No increased incidence of narcolepsy was observed among children under the age of four or among adults over the age of 19.
In all the cases examined, narcolepsy associated with Pandemrix vaccination has been identified in persons who carry a genetic risk factor for narcolepsy. Because of this very strong association with the genetic risk factor which regulates immune responses, narcolepsy is considered an immune-mediated disease.
In approximately one quarter of those who developed narcolepsy following Pandemrix vaccination, the THL Immunology laboratory found antibodies binding to the AS03 adjuvant component of the vaccine. Adjuvants containing squalene have not previously been reported to induce the production of antibodies. The significance of this preliminary observation will be the subject of further research.
Tests on viral antibodies indicated that less than 10 per cent of the children and adolescents who developed narcolepsy had been infected with swine flu. Swine flu infection thus does not appear to play a significant role or be in joint effect with the Pandemrix vaccine in the onset of narcolepsy.
In addition to Finland, Sweden is so far the only other country which by using epidemiological research has confirmed an increase in narcolepsy cases associated with pandemic vaccination. In Sweden, too, the increased risk of narcolepsy has been observed specifically in children and adolescents. The added risk associated with vaccination was about three cases of narcolepsy in every 100 000 persons vaccinated. Norway and France also report more than the number of expected cases of narcolepsy among children and adolescents who received the Pandemrix vaccine. However, in the absence of data on people who were not vaccinated, a reliable assessment on the possible link with the vaccine cannot be made in these countries. Several studies on the association between pandemic vaccine and narcolepsy are underway in countries where considerable numbers of Pandemrix or Arepanrix, a pandemic vaccine with a similar composition, were used.
By 25 August 2011, the National Vaccine Adverse Event Register maintained by THL had received notifications of 98 cases of narcolepsy subsequent to vaccination with Pandemrix; 79 of the subjects were between 4–19 years old at the time of vaccination. Narcolepsy was associated with cataplexy in 78 of the cases. Most of the persons affected developed symptoms within a couple of months after receiving the vaccination.
The evidence produced by the Task Force concerning the association between narcolepsy and Pandemrix vaccination observed in Finland played a crucial role in the European Medicines Agency’s assessment of the observation, which led to a recommendation for limiting the use of Pandemrix vaccine. The European Medicines Agency considered the epidemiological studies carried out in Finland and Sweden to be well planned, and considered that the results indicated an association between Pandemrix vaccine and the cases of narcolepsy affecting children and young people in those countries. The European Medicines Agency recommends that the use of Pandemrix among those below 20 years of age should be limited to situations where seasonal influenza vaccine is not available and if the person requires protection from the swine flu virus because of being at risk of developing a severe form of the disease or its complications.
The Pandemrix vaccine was used in the winter of 2009–2010 to prevent the swine flu epidemic. About half of the Finnish population chose to be vaccinated. In autumn 2009 at the peak of the epidemic, the daily number of people (mainly under the age of 65) in hospital care was 400, with more than 50 patients in intensive care. There were 44 deaths from swine flu confirmed by laboratory tests. A significant number of severe cases were prevented during the 2009–2010 season, even if vaccines were given at about the same time as the epidemic reached Finland. Vaccinations of the groups most at risk from swine flu were completed by the local authorities before the first wave of the epidemic struck.
During the influenza season 2010–2011, 52 persons were treated in intensive care, and 13 succumbed. Most of these were unvaccinated. Combining the data on morbidity and mortality with data on vaccinations in the 2009–2010 pandemic season indicate that a swine flu vaccination taken in the pandemic season had provided 75–88 per cent protection against the swine flu virus in winter 2010–2011. Based on these vaccine effectiveness figures, it has been estimated that during the first wave in 2009-2010, the swine flu vaccine prevented approximately 40 000 cases of swine flu, and during the second wave in 2010-2011, another 40 000 cases of swine flu.
The Task Force concurs with the European Medicines Agency’s estimate that, despite the unforeseen and deeply regrettable cases of narcolepsy, the overall benefit-risk balance remains positive.
Further research is needed to fully understand the association between narcolepsy and Pandemrix, in order to avoid similar adverse events in future. Different research teams in Finland and other countries continue with research on the immunogenetics, pathogenesis, and the development of the clinical course of narcolepsy.
In 2010, a sudden increase was observed in Finland in the incidence of narcolepsy among children and adolescents who had received pandemic vaccine. In September 2010, the Director General of THL appointed a National Narcolepsy Task Force to investigate the potential association between the pandemic vaccination and narcolepsy. At the same time, THL initiated immunogenetic and virological studies in order to gain a deeper understanding of the observation. In its Interim Report, published on 31 January 2011, the Task Force concluded that the risk of narcolepsy among those vaccinated with Pandemrix in the age group 4–19 years was several times that of unvaccinated children in the same age group.
European Medicines Agency press release, 21 July 2011 (pdf)
Director of Department
chair of National Narcolepsy Task Force
tel. 020 610 8678
Vaccine Safety Officer
secretary of National Narcolepsy Task Force
tel. 020 610 8246
Head of Immune Response Unit
tel. +358 20 610 8463
Short address: http://www4.thl.fi/doc/en/26352
Updated 1 Sep 2011