- Carola Bardage, epidemiologist1,
- Ingemar Persson, professor of pharmacoepidemiology and senior expert12,
- Åke Örtqvist, county medical officer and associate professor34,
- Ulf Bergman, professor of pharmacoepidemiology and clinical pharmacologist25,
- Jonas F Ludvigsson, paediatrician and epidemiologist26,
- Fredrik Granath, senior biostatistician2
- 1Medical Products Agency, PO Box 26, SE-751 03, Uppsala, Sweden
- 2Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden
- 3Department of Communicable Diseases Control and Prevention, Stockholm County Council, Sweden
- 4Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
- 5Regional Drug Safety Unit, Division of Clinical Pharmacology, Karolinska Institute, Stockholm, Sweden
- 6Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
- Correspondence to: C Bardage
- Accepted 26 August 2011
Objective To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months.
Design Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period.
Setting Stockholm county, Sweden.
Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1 024 019 were vaccinated against H1N1 and 921 005 remained unvaccinated.
Main outcome measures Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell’s palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status.
Results Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell’s palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0.94, 0.91 to 0.98), whereas those vaccinated in the late phase had an overall reduced mortality (0.68, 0.64 to 0.71). These associations could be real or explained, partly or entirely, by residual confounding.
Conclusions Results for the safety of Pandemrix over 8-10 months of follow-up were reassuring —notably, no change in the risk for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, or rheumatoid arthritis. Relative risks were significantly increased for Bell’s palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign. Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions.
We thank Peter Rönnerfalk, chief medical officer, Stockholm County Council, for supporting this study, to be done within the county without external funding.
Contributors: CB, IP, ÅÖ, FG, and UB conceived and designed the study. FG analysed the data. All authors (CB, IP, ÅÖ, FG, JFL, and UB) interpreted the data, critically revised and prepared the manuscript, and gave final approval of the version to be published. CB is the guarantor. This manuscript represents the views of the authors, not necessarily those of the Swedish drug regulatory agency (Medical Products Agency) where two of the authors are employed (CB, IP)
Funding: Stockholm County Council and the Medical Products Agency.
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: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the regional ethics committee in Stockholm, Sweden (No 2010/773-31/1 and 2010/1772-32).
Data sharing: No additional data available.
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