Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists

Arthritis Rheum. 2005 Jun;52(6):1766-72. doi: 10.1002/art.21043.


Objective: To investigate the impact of official recommendations regarding the management of latent tuberculosis (TB) infection on the rate of active TB in patients receiving treatment with tumor necrosis factor (TNF) antagonists.

Methods: Data on active TB rates and on screening and treatment of latent TB infection were extracted from the BIOBADASER (Spanish Society of Rheumatology Database on Biologic Products), a registry of patients with rheumatic conditions treated with TNF antagonists. The rates of active TB among the BIOBADASER patients were compared with those in the background Spanish population, and BIOBADASER patients with rheumatoid arthritis (RA) were compared with a cohort of RA patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study who were not treated with TNF antagonists and were followed up for 5 years.

Results: Active TB developed in 34 patients, of whom 32 started taking TNF antagonists prior to the official recommendations on latent TB infection (pre-OR) and 2 began treatment after the recommendations were issued (post-OR). All cases of TB occurred during treatment with infliximab, and 28 of these patients had RA. Pre-OR, the active TB rate in BIOBADASER patients was 20.9-fold higher than in the background Spanish population, while RA patients in the BIOBADASER had rates 22.6- and 6.2-fold higher than the background and EMECAR populations, respectively. Post-OR, 324 patients with a tuberculin skin test result > or =5 mm and/or chest radiograph findings suggestive of past TB were treated for 9 months with isoniazid (INH). Post-OR, active TB rates among the BIOBADASER patients decreased by 78% (incidence risk ratio [IRR] 0.22, 95% confidence interval [95% CI] 0.03-0.88; P = 0.008), while among RA patients in the BIOBADASER, the rate dropped by 83% and reached the EMECAR rate (IRR 1.0, 95% CI 0.02-8.2). There were no INH treatment-related hospitalizations or deaths.

Conclusion: Strategies to treat latent TB infection that are tailored to the at-risk population can effectively and safely lessen the likelihood of active TB in patients treated with TNF antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy
  • Etanercept
  • Female
  • Health Planning Guidelines
  • Humans
  • Immunoglobulin G / adverse effects
  • Infliximab
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor
  • Rheumatic Diseases / drug therapy*
  • Secondary Prevention
  • Treatment Outcome
  • Tuberculosis / chemically induced
  • Tuberculosis / etiology*
  • Tuberculosis / prevention & control*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept