Article Text

This article has a correction. Please see:

Download PDFPDF
Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
  1. Johan Askling1,
  2. C Michael Fored1,
  3. Lena Brandt1,
  4. Eva Baecklund3,
  5. Lennart Bertilsson4,
  6. Nils Feltelius2,5,
  7. Lars Cöster6,
  8. Pierre Geborek7,
  9. Lennart T Jacobsson8,
  10. Staffan Lindblad2,
  11. Jörgen Lysholm9,
  12. Solbritt Rantapää-Dahlqvist10,
  13. Tore Saxne7,
  14. Ronald F van Vollenhoven2,
  15. Lars Klareskog2
  1. 1
    Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
  2. 2
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
  3. 3
    Department of Rheumatology, Uppsala University Hospital, Uppsala, Sweden
  4. 4
    Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden
  5. 5
    Medical Products Agency, Uppsala, Sweden
  6. 6
    Department of Rheumatology, Linköping University Hospital, Linköping, Sweden
  7. 7
    Department of Rheumatology, Lund University Hospital, Lund, Sweden
  8. 8
    Department of Rheumatology, Malmö University Hospital, Malmö, Sweden
  9. 9
    Department of Rheumatology, Falu County Hospital, Falun, Sweden
  10. 10
    Department of Rheumatology, University Hospital, Umeå, Sweden
  1. Johan Askling, Clinical Epidemiology Unit, M9:01, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden; johan.askling{at}


Objectives: The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.

Methods: First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.

Results: Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.

Conclusion: Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding: Financial support for this study was obtained from Wyeth-Ayerst, Schering-Plough, Abbott Immunology and Bristol Myer Squibb. The investigators were in charge of and solely responsible for all data collection, analysis and writing of the manuscript, without any constraints exerted from the agencies or companies that helped to sponsor the study. The South Swedish Anti-TNF Register has received funding from King Gustav V, Österlund and Kock Foundations, and from Reumatikerförbundet.

  • Competing interests: None.

  • Abbreviations:
    Disease Activity Score
    disease-modifying anti-rheumatic drug
    Health Assessment Questionnaire
    non-steroidal anti-inflammatory drug
    rheumatoid arthritis
    relative risk
    tumour necrosis factor

Linked Articles

  • Correction
    BMJ Publishing Group Ltd and European League Against Rheumatism