Paris Descartes University, Medicine Faculty, UPRES-EA 4058, 75651 Paris, France.
Joint Bone Spine. 2010 Mar;77(2):135-41. doi: 10.1016/j.jbspin.2009.10.012. Epub 2010 Jan 25.
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.
To assess (a) frequency of prescription, (b) reasons for prescription, (c) tolerance of INH/RIF for prevention of tuberculosis.
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.
patients'demographic characteristics, reasons of prescription, tolerance and levels of aminotransferase before and during INH/RIF treatment.
Descriptive and determination of risk factors of hepatotoxicity by multivariate logistic regression.
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.
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.
肿瘤坏死因子(TNF)阻滞剂会增加结核感染的风险。法国针对潜伏性结核预防的国家建议采用利福平(RIF)600mg/天和异烟肼(INH)300mg/天的方案进行 3 个月的治疗。然而,在此背景下,其毒性尚不清楚,存在争议。
评估(a)预防性应用的频率,(b)处方的原因,(c)预防结核应用 INH/RIF 的耐受性。
对 2002 年至 2007 年期间在一家三级风湿病单位接受 TNF 阻滞剂治疗的所有患者的医疗记录进行了系统的回顾性研究,这些患者均接受过 INH/RIF 治疗。
患者的人口统计学特征、处方的原因、INH/RIF 治疗期间的耐受性和氨基转移酶水平。
描述性分析和通过多变量逻辑回归确定肝毒性的危险因素。
在 2002 年至 2007 年间接受 TNF 阻滞剂治疗的 1028 例患者中,有 216 例(21.1%)接受了 INH/RIF 治疗。在有完整数据的 93 例患者中,有 17 例(18.2%)出现了肝毒性,其中只有 1 例超过了正常值上限的 10 倍。有 14 例(15.0%)出现了其他副作用。有 10 例(10.7%)患者因不耐受而中断了 INH/RIF 治疗。预测不耐受的因素包括男性、治疗前的氨基转移酶、较高的体重指数和来氟米特联合用药。
这项系统的病例回顾表明,需要预防性应用 INH/RIF 的必要性很高,特别是对于结核菌素皮肤试验阳性的患者。这种联合用药的肝毒性发生率较高,但无严重后果。在预防性治疗前需要更好地筛选患者。