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Risk of presentation to hospital with epileptic seizures after vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix): self controlled case series study

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7594 (Published 28 December 2012) Cite this as: BMJ 2012;345:e7594
  1. Lisen Arnheim-Dahlström, research associate,
  2. Jonas Hällgren, statistician,
  3. Caroline E Weibull, statistician,
  4. Pär Sparén, professor
  1. 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77 Stockholm, Sweden
  1. Correspondence to: L Arnheim-Dahlström lisen.arnheim.dahlstrom{at}ki.se
  • Accepted 2 November 2012

Abstract

Objective To assess the risk of epileptic seizures in people with and without epilepsy after vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix; Glaxo SmithKline, Sweden).

Design Register based self controlled case series.

Setting Three Swedish counties (source population 750 000).

Participants 373 398 people (age 0-106, median 41.2) who were vaccinated. Vaccinated people with epileptic seizures, diagnosed as inpatients or outpatients, at any time from 90 days before until 90 days after any dose of vaccine.

Main outcome measures Endpoints were admission to hospital or outpatient hospital care with epileptic seizures as the main diagnosis. The effect estimate of relative incidence was calculated as the incidence of epileptic seizures in period after exposure relative to the incidence of epileptic seizures in two control periods, one before and one after vaccination.

Results 859 people experienced epileptic seizures during the study period. There was no increased risk of seizures in people with previously diagnosed epilepsy (relative incidence 1.01, 95% confidence interval 0.74 to 1.39) and a non-significant decrease in risk for people without epilepsy (0.67, 0.27 to 1.65) during the day 1-7 risk period (where day 1 is the day of vaccination). In a second risk period (day 8-30), there was a non-significant increased risk of seizures in people without epilepsy (1.11, 0.73 to 1.70) but no increase in risk for those with epilepsy (1.00, 0.83 to 1.21).

Conclusions This study found no evidence of an increase in risk of presentation to hospital with epileptic seizures after vaccination with a monovalent AS03 adjuvanted pandemic H1N1 influenza vaccine.

Footnotes

  • We thank Harald Heijbel (an expert in vaccine safety) at the Swedish Institute for Infectious Disease Control for feedback on the manuscript. We also thank Vincent Guy Bauchan and Dominique Rosillon at GlaxoSmithKline Biologicals for feedback on the statistical analysis and on the draft manuscript.

  • Contributors: PS, LAD, and JH were responsible for the study design. LAD collected the data. JH created the database, performed the statistical analysis, and drafted the statistical methods section. LAD drafted the manuscript with PS. CEW performed the statistical analysis together with JH. All authors actively participated in the interpretation of the results and discussed and approved the final version. PS is guarantor.

  • Funding: This work was supported by a grant from GlaxoSmithKline Biologicals in Belgium. The authors had full access to all the data in the study and had the full responsibility to submit the report for publication. The opinions presented in the report do not necessarily reflect those of the funders.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that all the authors received unconditional grants from GlaxoSmithKline for the submitted study.

  • Ethical approval: The study was approved by the ethical review board in Stockholm.

  • Data sharing: The analysis dataset for this study can be made available to other researchers on request to the authors.

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