Stanford University, Palo Alto, CA, USA.
Ann Rheum Dis. 2010 Sep;69(9):1612-7. doi: 10.1136/ard.2009.112136. Epub 2010 May 6.
Liver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007.
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >1x upper limit of normal (ULN) were considered elevations and ALT/AST levels >2x ULN were considered abnormalities. Treatments included TNF-Is, methotrexate (MTX), leflunomide and other disease-modifying antirheumatic agents (DMARDs). Patients were censored after their first LFT elevation. Three analytical models were evaluated: (1) individual TNF-I vs non-biological DMARDs (primary model); (2) individual TNF-I plus MTX vs MTX monotherapy; and (3) limited to new users of individual TNF-I vs non-biological DMARDs. ORs for LFT elevations were estimated using generalised estimating equation logistic regression.
6861 patients (ADA: 849; ETN: 1383; INF: 1449) with 22 522 determinations were analysed. LFT elevations >1x ULN with TNF-I use were seen in 5.9% of AST/ALT determinations and abnormalities >2x ULN in 0.77%. In the primary model the adjusted ORs for LFT elevations >1x ULN were ADA 1.35 (95% CI 1.09 to 1.66), ETN 1.00 (95% CI 0.83 to 1.21) and INF 1.58 (95% CI 1.35 to 1.86). For 2x ULN, adjusted ORs were ADA 1.72 (95% CI 0.99 to 3.01), ETN 1.10 (95% CI 0.64 to 1.88) and INF 2.40 (95% CI 1.53 to 3.76). Similar results were obtained in other models.
The overall incidence of LFT elevations >1x ULN with TNF-I use was uncommon and abnormalities >2x ULN were rarely observed. Significant differences were most consistently observed with INF, less commonly with ADA and were not observed with ETN compared with comparator DMARDs.
肿瘤坏死因子抑制剂（TNF-Is）的使用会导致肝功能测试（LFT）升高。本研究旨在比较 2001 年 10 月至 2007 年 3 月期间，加入北美风湿病研究联合会的类风湿关节炎患者在接受阿达木单抗（ADA）、依那西普（ETN）或英夫利昔单抗（INF）治疗时 LFT 升高的情况。
丙氨酸氨基转移酶（ALT）和/或天冬氨酸氨基转移酶（AST）水平>1x 正常值上限（ULN）被认为是升高，而 ALT/AST 水平>2x ULN 则被认为是异常。治疗包括 TNF-Is、甲氨蝶呤（MTX）、来氟米特和其他疾病修正抗风湿药物（DMARDs）。患者在首次 LFT 升高后被删失。评估了三种分析模型：（1）单独 TNF-I 与非生物 DMARDs（主要模型）；（2）单独 TNF-I 加 MTX 与 MTX 单药治疗；（3）限制为单独 TNF-I 的新使用者与非生物 DMARDs。使用广义估计方程逻辑回归估计 LFT 升高的比值比（OR）。
对 6861 例患者（ADA：849 例；ETN：1383 例；INF：1449 例）的 22522 次测定进行了分析。TNF-I 治疗后，AST/ALT 测定值中 LFT 升高>1x ULN 的比例为 5.9%，>2x ULN 的比例为 0.77%。在主要模型中，LFT 升高>1x ULN 的调整后 OR 分别为 ADA 1.35（95%CI 1.09-1.66）、ETN 1.00（95%CI 0.83-1.21）和 INF 1.58（95%CI 1.35-1.86）。对于 2x ULN，调整后的 OR 分别为 ADA 1.72（95%CI 0.99-3.01）、ETN 1.10（95%CI 0.64-1.88）和 INF 2.40（95%CI 1.53-3.76）。在其他模型中也得到了类似的结果。
TNF-I 治疗后 LFT 升高>1x ULN 的总体发生率并不常见，>2x ULN 的异常情况很少观察到。与比较 DMARDs 相比，INF 观察到的差异最显著，ADA 次之，而 ETN 则没有观察到。
