title: Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
abstract: 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.
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Arkema
authors.affiliation: Swedish Institute for Infectious Disease Control, Solna, Sweden Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jerker
authors.initials: J
authors.lastname: Jonsson
authors.affiliation: Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
authors.affiliation: Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Judith
authors.initials: J
authors.lastname: Bruchfeld
authors.affiliation: Medical Products Agency, Uppsala, Sweden Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Feltelius
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D001688:Biological Products / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: Anti-TNF; Rheumatoid Arthritis; Treatment; Tuberculosis