Bourré-Tessier Josiane, Arino-Torregrosa Mireia, Choquette Denis
Department of Medicine, Division of Rheumatology, University of Montreal Hospital Research Center and Institut de Rhumatologie de Montréal, Montréal, Québec, Canada,
Clin Rheumatol. 2014 Aug;33(8):1049-53. doi: 10.1007/s10067-014-2528-z. Epub 2014 Feb 21.
Reactivation of latent tuberculosis (LTB) has been described with the use of anti-TNFs. Combined treatment of isoniazid (INH) and disease modifying antirheumatic drugs (DMARDs) can potentially increase the risk of hepatotoxicity. The goal of this study was to investigate the risk of hepatotoxicity in rheumatic patients taking INH while on DMARDs and/or biologics. We reviewed the Institut de Rhumatologie de Montréal database (Rhumadata®) for rheumatic patients with positive tuberculin skin test or quantiFERON who took INH between August 2001 and April 2011. Liver function tests (LFTs) were collected at baseline and during therapy, and LFTs up to 9 months prior to INH initiation were used as controls. Of 922 patients screened for LTB, 87 patients tested positive. During INH treatment, 75.9 % were taking DMARDs, 82.8 % were taking biologics. A total of 375 LFTs performed while on INH were compared to 211 available tests collected prior to INH therapy. Twenty-four percent of the patients had abnormal LFTs during INH compared to 12.1 % prior to INH (p = 0.0481). Most of these abnormalities were mild or transient, but 8 % (seven patients) had significant abnormalities leading to INH discontinuation. Among these patients, mean (min, max) was 241 (52, 617) for AST and 262 (92, 669) for ALT. Although the use of INH therapy in combination with DMARDs and/or biologics was generally well tolerated, the rate of LFT abnormalities was higher when patients were exposed to INH, and significant abnormalities were more frequent than reported in the INH literature. It is prudent to closely follow the LFTs of these patients.
已有报道使用抗TNF药物会导致潜伏性结核（LTB）复发。异烟肼（INH）与改善病情抗风湿药（DMARDs）联合治疗可能会增加肝毒性风险。本研究的目的是调查服用INH的风湿性疾病患者同时使用DMARDs和/或生物制剂时发生肝毒性的风险。我们回顾了蒙特利尔风湿病研究所数据库（Rhumadata®）中2001年8月至2011年4月期间结核菌素皮肤试验或全血γ干扰素释放试验呈阳性且服用INH的风湿性疾病患者。在基线和治疗期间收集肝功能检查（LFTs）结果，并将INH开始使用前9个月内的LFTs结果作为对照。在922例接受LTB筛查的患者中，87例检测呈阳性。在INH治疗期间，75.9%的患者同时服用DMARDs，82.8%的患者同时服用生物制剂。将INH治疗期间进行的375次LFTs结果与INH治疗前收集的211次可用检查结果进行比较。与INH治疗前12.1%的患者相比，24%的患者在INH治疗期间LFTs结果异常（p = 0.0481）。这些异常大多为轻度或短暂性，但8%（7例患者）出现严重异常，导致停用INH。在这些患者中，天冬氨酸转氨酶（AST）的平均值（最小值，最大值）为241（52，617），丙氨酸转氨酶（ALT）的平均值（最小值，最大值）为262（92，669）。虽然INH与DMARDs和/或生物制剂联合治疗总体耐受性良好，但患者接受INH治疗时LFTs异常率更高，严重异常情况比INH相关文献报道的更为频繁。密切监测这些患者的LFTs结果是谨慎之举。
