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Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
  1. Elizabeth V Arkema1,
  2. Jerker Jonsson2,3,
  3. Eva Baecklund4,
  4. Judith Bruchfeld3,
  5. Nils Feltelius5,6,
  6. Johan Askling1,6
  7. on behalf of the ARTIS Study Group
  1. 1Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2Swedish Institute for Infectious Disease Control, Solna, Sweden
  3. 3Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  4. 4Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  5. 5Medical Products Agency, Uppsala, Sweden
  6. 6Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Elizabeth V Arkema, Clinical Epidemiology Unit, T2, Karolinska Institutet, Stockholm 17176, Sweden; Elizabeth.Arkema{at}


Objective To estimate the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) both with and without exposure to biological therapy and to directly compare the risks between therapies.

Methods Data from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002–2011). We estimated the rate of incident TB in the general population and in a cohort of biological-naïve and biological-exposed patients diagnosed with RA. Cox models were used to estimate HRs with particular attention to risks by calendar and follow-up time and individual biologics.

Results Compared to the general population, RA patients not exposed to biologicals had a fourfold increased risk of TB (HR 4.2; 95% CI 2.7 to 6.7), which did not decline over calendar time. In contrast, the risk of TB in the biological-exposed RA population decreased since 2002 compared with biological-naïve; from HR=7.9 (95% CI 3.3 to 18.9) in 2002–2006 to HR=2.4 (95% CI 0.9 to 6.1) in 2007–2011. The HRs for most recent exposure to adalimumab and infliximab compared with etanercept were 3.1 (95% CI 0.8 to 12.5) and 2.7 (95% CI 0.7 to 10.9), respectively, and the HR for etanercept compared with biological-naïve RA was 1.7 (95% CI 0.6 to 4.6).

Conclusions In the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in biological-naïve RA patients, underscoring the elevated risk also in these patients.

  • Rheumatoid Arthritis
  • Tuberculosis
  • Anti-TNF
  • Treatment

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