Frequency and tolerance of antituberculosis treatment according to national guidelines for prevention of risk of tuberculosis due to tumor necrosis factor blocker treatment

Joint Bone Spine. 2010 Mar;77(2):135-41. doi: 10.1016/j.jbspin.2009.10.012. Epub 2010 Jan 25.


Purpose: Tumor necrosis factor (TNF) blockers increase the risk of tuberculosis infection. National recommendations in France for prevention of latent tuberculosis recommend treatment by rifampicin (RIF) 600 mg/day and isoniazid (INH) 300 mg/day for 3 months. However, its toxicity is unknown in this context and is a subject of debate.

Objective: To assess (a) frequency of prescription, (b) reasons for prescription, (c) tolerance of INH/RIF for prevention of tuberculosis.

Methods: Systematic retrospective study of medical records of one tertiary rheumatology unit, from 2002 to 2007, of all patients who were prescribed INH/RIF before receiving TNF blockers.

Data collection: patients'demographic characteristics, reasons of prescription, tolerance and levels of aminotransferase before and during INH/RIF treatment.

Analysis: Descriptive and determination of risk factors of hepatotoxicity by multivariate logistic regression.

Results: Of 1028 patients treated by TNF blockers between 2002 and 2007, 216 (21.1%) received INH/RIF treatment. Of 93 patients with complete data, 17 (18.2%) presented hepatotoxicity of which only one above 10 times the upper limit of the norm. Fourteen (15.0%) had other side effects. Ten (10.7%) patients had to interrupt INH/RIF for intolerance. Factors predicting intolerance were male sex, aminotransferases before treatment, a higher body mass index and leflunomide comedication.

Conclusion: This systematic case review indicates a high rate of necessity for preventive treatment by INH/RIF, and in particular for positive skin tests. This association had a high rate of hepatotoxicity without severe consequences. A better screening of patients before preventive therapy is needed.

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Databases, Factual
  • Female
  • Humans
  • Immunocompromised Host
  • Isoniazid / administration & dosage
  • Isoniazid / adverse effects
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Practice Guidelines as Topic
  • Retrospective Studies
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / epidemiology
  • Rheumatic Diseases / immunology
  • Rifampin / administration & dosage
  • Rifampin / adverse effects*
  • Risk Factors
  • Severity of Illness Index
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / prevention & control*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antitubercular Agents
  • Tumor Necrosis Factor-alpha
  • Isoniazid
  • Rifampin