Swine flu  Pandemrix  Narcolepsy  Sweden

A Swedish registry based cohort study provides strengthened evidence of an association between vaccination with Pandemrix and narcolepsy in children and adolescents

March 29, 2011

Results from a Swedish registry based cohort study indicate a 4-fold increased risk of narcolepsy in children and adolescents below the age of 20 vaccinated with Pandemrix, compared to children of the same age that were not vaccinated. The results are in line with those of a similar Finish registry study.

The Medical products Agency (MPA) has in co-operation with the healthcare regions of Skåne and Västra Götaland, the county councils of Östra Götaland and Stockholm and with the Karolinska Institutet performed a study of a possible relationship between vaccination with Pandemrix and the occurrence of narcolepsy.

All cases of diagnosed narcolepsy reported to the healthcare databases in these four regions between October 1st  2009 and December 31st  2010 have been linked to information in the regional vaccination databases. These four regions have around 5.3 million inhabitants, which corresponds roughly to 57 percent of the Swedish population. The vaccination coverage was on average 67 % for children and adolescents under the age of 20 and 51 % for adults.

The study shows a 4-fold increased risk for children and adolescents vaccinated with Pandemrix to be diagnosed with narcolepsy as compared with unvaccinated subjects (4,06 cases per 100 000 person years in vaccinated children/adolescents compared with 0,97 cases per 100 000 person years in unvaccinated). This risk would translate into an absolute risk of three cases of narcolepsy in 100 000 vaccinated children/adolescents. No increased risk was seen in adults.

There is still some uncertainty regarding the magnitude of the increased risk. The study does not take into consideration whether individuals with an increased risk of narcolepsy also to a greater extent were vaccinated compared to individuals without risk factors. The fact that a similar increase in risk is not seen in adults contradicts the presence of important differences in risk factors between the groups. Neither has it been possible to relate the occurrence of the first symptoms of narcolepsy to the time for vaccination. The MPA is however of the opinion that even if the estimated magnitude of the increased risk can change after further analyses it is not plausible that the differences in risk will disappear.

The results of this Swedish study are in line with those recently reported from from the registry study in Finland. The Finnish study showed a nine-fold increased risk for narcolepsy in adolescents and children 19 years old and younger. When the Finnish study results had been presented, and considering that the risk of getting ill with H1N1 influenza at present is very small, the MPA concluded that vaccination of children and adolescents with Pandemrix for the time being should not be recommended. This position has been further strengthened on account of the new Swedish data. Concerned Swedish authorities have been informed on the conclusions drawn by the MPA and on the results of the new Swedish study.

The MPA will continue the investigation in order to seek explanations to the increased risk of narcolepsy in children and adolescents shown in the registry studies and to the observation that an association between Pandemrix and narcolepsy seems to be present only in Sweden and Finland.  An ongoing case inventory study - aiming at identifying and examining all new Swedish cases of narcolepsy that have occurred 2009-2010 by means of data from the medical records and through expert evaluations - is one part of this investigation. The study is expected to give further support to the results of the registry study and will hopefully contribute with new knowledge on the clinical course of the disease and possible risk factors. These results are expected to be available this summer.

In an additional epidemiological study, conducted by the Karolinska Institutet in co-operation with research institutions in eight European countries, cases of narcolepsy will be compared with healthy controls. The main objective of this initiative is to study whether vaccination with Pandemrix alone influences the risk or whether the increased risk occurs through interaction with other factors, like for example influenza infection in connection with or directly after the vaccination. Within this European collaborative study it may be possible to compare the results for the three different H1N1 influenza vaccines that have been used in Europe.