Is the risk of narcolepsy also increased with non-adjuvanted flu vaccines?BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f2769 (Published 13 May 2013) Cite this as: BMJ 2013;346:f2769
- Lennart Waldenlind, pharmacovigilance assessor1,
- Birgitta Grundmark, pharmacovigilance assessor12,
- Faranak Azarbayjani, pharmacovigilance assessor13,
- Andreas Börjesson, pharmacovigilance assessor1,
- Hans Olaisson, pharmacovigilance assessor1
- 1Department of Pharmacovigilance, Medical Products Agency, PO Box 26, SE-751 03 Uppsala, Sweden
- 2Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
- 3Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
In line with previous studies, Miller and colleagues find an increased risk of narcolepsy after vaccination with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix; odds ratio 16.2, 95% CI 3.1 to 84.5) and call for similar studies on other flu vaccines.1
Several flu vaccines are available in Europe, both adjuvanted and non-adjuvanted. All suspected adverse vaccine reactions must be reported to pan-European database EudraVigilance (www.adrreports.eu), which will soon be fully publicly accessible. The first suspected case of narcolepsy associated with a non-adjuvanted flu vaccine was reported in August 2010. By September 2012, the number of cases increased to 18, 15 of which seem to be medically verified. In most cases, symptoms developed abruptly after onset of typical first symptoms (such as cataplexy and sleeping attacks), as reported for Pandemrix related cases. Half (nine) of the cases originate from the European Union area, with eight coming from the US and one from Taiwan. More than half (10/18) are children or adolescents (≤18 years), with most testing positive (seven of eight) for the predisposing HLA gene DQB10606. Genotyping was not specified for any of the patients over 18 years. The time between vaccination and symptom onset was detailed in 13 of the 18 cases and averaged two to three months. In another three cases, estimated onset time varied between less than three months and six months.
Potential explanatory factors are use of Pandemrix or flu infection. In two cases Pandemrix was given at the same time as the non-adjuvanted vaccine or one year before symptom onset, but flu was not reported in any of the cases. Thus, no potential confounding was reported in 16 of the 18 cases.
The mechanism of Pandemrix induced narcolepsy is still unclear. A review article emphasises that “It is important to note that influenza infection can also trigger narcolepsy, and that this is a property of the influenza virus antigens rather than any particular vaccine or its adjuvant.”2
Narcolepsy is extremely rare, and the discovery of its association with Pandemrix through spontaneous reporting was facilitated by the short term massive exposure in at risk age groups. The recent cluster of cases related to non-adjuvanted flu vaccines, where the exposure pattern was different, supports Miller and colleagues’ view that further studies are needed to assess the risk for flu vaccines other than Pandemrix.
Cite this as: BMJ 2013;346:f2769
Competing interests: None declared.
The views in this letter represent those of the authors and not necessarily those of the Swedish Medical Products Agency where the authors are (partly) employed.