A UK study of GlaxoSmithKline’s flu vaccine Pandemrix has concluded that there appears to be a link between the product and the sleep disorder narcolepsy, backing up earlier findings from Finland and Sweden.
Researchers from the UK Health Protection Agency (HPA) carried out a retrospective analysis on children and adolescents vaccinated with the swine flu shot between 2009 and 2011, at the height of fears of a possible pandemic.
The retrospective analysis – published in the British Medical Journal – looked at case notes for 245 children and found that 75 were diagnosed with narcolepsy, of whom 11 had been vaccinated with Pandemrix before the onset of symptoms and seven of them within six months.
They concluded that children developing narcolepsy were 14 times more likely to have been vaccinated at any time before symptoms of the sleep disorder were discovered, and 16 times more so if Pandemrix had been given within the prior six months.
Overall, that implies a risk of one case of narcolepsy per 52,000-57,500 doses, lower than the 1 in 16,000 estimate reported in Finland but still higher than the background incidence of the disease.
In April 2011 the European Medicines Agency (EMA) recommended that Pandemrix’ label be updated to include information about a possible increased risk of narcolepsy in children and advised healthcare professionals to perform an individual benefit-risk assessment for each patient.
The HPA researchers note that there are limitations in their study which could mean there is no causal link. Aside from the small numbers involved in the study and the difficulty in defining narcolepsy symptoms, they speculate that referrals could have been accelerated, which would have increased the relative risk.
Meanwhile, Pandemrix might accelerate onset of narcolepsy in a child destined to develop the condition anyway, but not actually increase the risk of developing the disorder, they suggest.
The mechanism behind the reaction remains entirely speculative, but the scientists suggested one possible explanation could be that the AS03 adjuvant used in Pandemrix may trigger an immune reaction against cells involved in sleep regulation in children who were genetically predisposed to develop the disorder.
GSK said it is sifting through the available data to try to understand whether there is any association between Pandemrix and narcolepsy, but for now maintains there is no clear evidence of a causal link. Additional data may become available when it completes a study of a similar pandemic flu vaccine – called Arepanrix – in Canada later this year.
Arepanrix also contains the AS03 adjuvant and was administered to 16 million people, providing another large patient population to help assess risk.