The Medical Products Agency in Sweden has conducted a Case Inventory Study which provides strengthened evidence for an association between vaccination with Pandemrix and narcolepsy in children and adolescents, 19 years and younger.
When the Medical Products Agency (MPA) in 2010 received an unexpectedly large number of reports of cases of narcolepsy in children and adolescents, with a suspected association with Pandemrix, the MPA initiated further investigations in cooperation with national experts.
In March 2011 the MPA reported on the results of a Swedish registry based study covering four counties/regions that comprise 57 percent of the Swedish population. The study showed a four-fold higher risk for children and adolescents of being diagnosed with narcolepsy in those who were vaccinated with Pandemrix compared to those who were not vaccinated.
In order to make a more detailed examination of the development of narcolepsy in relation to pandemic vaccinations in Sweden, the MPA undertook the current case inventory study. In this study, information on all established and suspected cases of narcolepsy during 2009-2010, i.e. irrespective of vaccination status, was collected from relevant clinical departments and sleep laboratories. Medical records were scrutinized by experts in order to verify the diagnosis of narcolepsy with cataplexy according to established criteria and to determine the time of onset of first symptoms. Information on vaccination status was collected from separate records.
This study focused specifically on cases of narcolepsy with cataplexy occurring in children/ adolescents 19 years and younger.
The results of the study
132 medical records were identified and collected for review. 87 cases of narcolepsy with cataplexy were verified. Of these 87 cases, 81 could be included in the study since they had onset of first symptom within the study period January 1st 2009 – December 31st, 2010. Among the included patients 69 (85%) had been vaccinated with Pandemrix before onset of symptoms.
A pattern was noted when examining the occurrence (incidence) of narcolepsy with cataplexy in the entire population and over the two-year period. More individuals developed their first symptoms during the last quarter of 2009 and first quarter of 2010, i.e. in parallel with the pandemic activity and the national vaccination campaign.
The risk to develop narcolepsy with cataplexy among vaccinated subjects was calculated to be 4.2 cases per 100,000 persons per year; the risk among nonvaccinated subjects was 0.64 cases per 100,000 per year. Thus, the incidence was 6.6-fold higher among vaccinated children/ adolescents than those unvaccinated. These figures can also be expressed such that there were 3.6 additional cases of narcolepsy with cataplexy per 100 000 vaccinated subjects. For a few individuals, it was difficult to determine the onset of symptoms in relation to time of vaccination therefore the magnitude of the increased risk is uncertain and could be higher.
The results of the present case inventory study strengthen the growing evidence of an association between Pandemrix and narcolepsy with cataplexy in children / adolescents. The magnitude of the increased risk varies between the registry studies and the case inventory study; however, this fact does not influence the overall conclusion.
The causative mechanisms of the observed increased risk could not be explained by this study. The MPA will therefore collaborate with other authorities and scientists in the planning of further research needed. The MPA will also work to stimulate the introduction of tools for long term monitoring of the patients who have fallen ill with narcolepsy.
This study will be discussed at a European expert meeting, July 12. The report will be further assessed by the scientific committee (CHMP) of the EMA at its July meeting, together with scientific data from other countries, in the context of the ongoing safety examination.