Alves Jorge Augusto Nunes Rodrigues, Fialho Sonia Cristina de Magalhães Souza, Morato Edelton Flávio, Castro Gláucio RicardoWerner de, Zimmermann Adriana Fontes, Ribeiro Giovana Gomes, Neves Fabrício Souza, Pereira Ivânio Alves
Universidade Federal de Santa Catarina, Brazil.
Rev Bras Reumatol. 2011 Mar-Apr;51(2):141-4.
Some studies have reported that adding leflunomide (LEF) to the treatment of rheumatoid arthritis (RA) in patients who do not respond to methotrexate (MTX) improved efficacy but increased the risk of liver toxicity. This study aimed at assessing the incidence of liver toxicity in patients with active RA using the LEF and MTX combination therapy in comparison with that of patients on MTX monotherapy.
Between February and September 2009, 97 consecutive patients followed up at the University Hospital of the Universidade Federal de Santa Catarina, Brazil, were enrolled. RA patients on MTX alone or using the LEF and MTX combination had their medical records systematically reviewed. The alanine/aspartate aminotransferase enzymes were retrospectively analyzed since the beginning of treatment with MTX or MTX plus LEF. Hepatotoxicity was defined as an increase of at least two-fold the upper limits of normal of the liver enzymes.
71 RA patients were included in the study: 36.6% were using 20-25 mg/week of MTX alone and 63.4% were using 20-25 mg/week of MTX plus 20 mg/day of LEF. Of the patients on the combination therapy, 11.1% had abnormal levels of liver enzymes versus 11.5% of the patients on monotherapy (P = 1.0). Abnormal aminotransferase levels have been seen with both MTX and LEF monotherapies in patients with RA. In our study, no difference was found between the percentages of aminotransferase elevations of patients being treated with MTX alone or in combination with LEF.
The combination of MTX and LEF in RA patients is generally safe and well tolerated.
一些研究报告称，对于对甲氨蝶呤（MTX）无反应的类风湿关节炎（RA）患者，在治疗中加用来氟米特（LEF）可提高疗效，但会增加肝毒性风险。本研究旨在评估使用LEF和MTX联合疗法的活动性RA患者肝毒性的发生率，并与MTX单药治疗的患者进行比较。
2009年2月至9月，连续纳入了巴西圣卡塔琳娜联邦大学大学医院随访的97例患者。对单独使用MTX或使用LEF与MTX联合治疗的RA患者的病历进行了系统回顾。自开始使用MTX或MTX加LEF治疗以来，对丙氨酸/天冬氨酸转氨酶进行了回顾性分析。肝毒性定义为肝酶正常上限至少增加两倍。
71例RA患者纳入研究：36.6%的患者单独使用20 - 25mg/周的MTX，63.4%的患者使用20 - 25mg/周的MTX加20mg/天的LEF。联合治疗组中，11.1%的患者肝酶水平异常，单药治疗组为11.5%（P = 1.0）。RA患者使用MTX和LEF单药治疗时均出现了转氨酶水平异常。在我们的研究中，单独使用MTX或与LEF联合治疗的患者转氨酶升高的百分比之间没有差异。
RA患者使用MTX和LEF联合治疗总体上是安全的，耐受性良好。
