Latent tuberculosis infection detection and active tuberculosis prevention in patients receiving anti-TNF therapy: an Italian nationwide survey

Int J Rheum Dis. 2016 Aug;19(8):799-805. doi: 10.1111/1756-185X.12708. Epub 2015 Jul 14.

Abstract

Aims: Primary: to investigate Italian rheumatology practice regarding latent tubercular infection (LTBI) detection and tuberculosis (TB) prevention in patients requiring anti-tumor necrosis factor (anti-TNF) therapy. Secondary: to assess the overall number of TB cases over 10 years and their distribution by drug.

Methods: An anonymous, 24 multiple-response questionnaire was completed by 393/449 (87.5%) rheumatologists prescribing anti-TNF therapy. Six questions provided setting information, and 18 the compliance with recommendations and the recorded TB cases.

Results: The Italian recommendations were used by 323 (82%) and other sets by 60 (15%). TB specialists were always consulted by 81 (21%) and occasionally by 73 (19%). LTBI screening was made using chest radiograph (CR) by 5%, tuburculin skin test (TST) by 5.3%, CR + TST by 35.6%, interferon-gamma release assay (IGRA) by 7.4%, CR + IGRAs by 26% and CR + TST + IGRA by 20.6%. Isoniazid was initiated in the presence of positivity of TST by 97 (24.7%), TST + IGRA by 101 (25.7%) and IGRA by 195 (49.6%). Anti-TNF starting delay was 1 month in 63.1% of the cases, 3 months in 27.7%, concomitantly in 5.6%. Overall, 317 TB reactivation cases occurred in 39 353 patients, with an incidence rate of 80.5 cases/100 000/year (10 times higher than in the Italian general population). TB occurred during TB prophylaxis in 192 (60.6%). TB cases incidence rate divided by drug was: etanercept (ETN) 51 (16%), 28/100 000/year, adalimumab (ADA) 98 (31%), 89/100 000/year, infliximab (IFX) 137 (43.2%), 211/100 000/year, with a significantly lower frequency in the ETN group compared to ADA and IFX groups (χ(2) = P < 0.001).

Conclusion: Italian rheumatologists are highly aware of anti-TNF-related TB risk with variable LTBI screening and TB prevention strategies. TB outcome was significantly lower in the ETN group.

Keywords: anti-TNF; interferon-gamma release assays; latent tuberculosis infection; tuberculin skin test; tuberculosis.

MeSH terms

  • Adalimumab / adverse effects
  • Antirheumatic Agents / adverse effects*
  • Antitubercular Agents / therapeutic use
  • Biological Products / adverse effects*
  • Chi-Square Distribution
  • Etanercept / adverse effects
  • Guideline Adherence
  • Health Care Surveys
  • Humans
  • Immunocompromised Host*
  • Incidence
  • Infliximab / adverse effects
  • Italy / epidemiology
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / epidemiology
  • Latent Tuberculosis / immunology*
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / epidemiology
  • Opportunistic Infections / immunology*
  • Opportunistic Infections / prevention & control
  • Practice Guidelines as Topic
  • Practice Patterns, Physicians'
  • Predictive Value of Tests
  • Prognosis
  • Rheumatic Diseases / diagnosis
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / epidemiology
  • Rheumatic Diseases / immunology
  • Rheumatologists*
  • Risk Factors
  • Time Factors
  • Tuberculosis / diagnosis
  • Tuberculosis / epidemiology
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antirheumatic Agents
  • Antitubercular Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept