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

Abstract 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.