title: Frequency and tolerance of antituberculosis treatment according to national guidelines for prevention of risk of tuberculosis due to tumor necrosis factor blocker treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  patients'demographic characteristics, reasons of prescription, tolerance and levels of aminotransferase before and during INH/RIF treatment.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Paris Descartes University, Medicine Faculty, UPRES-EA 4058, 75651 Paris, France. marie-gaelle.bray@psl.aphp.fr
authors.forename: Marie-Gaëlle
authors.initials: MG
authors.lastname: Bray
authors.forename: Cécile
authors.initials: C
authors.lastname: Poulain
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000995:Antitubercular Agents; D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid; D012293:Rifampin