Din Shahida, Dahele Anna, Fennel Janice, Aitken Sue, Shand Alan G, Arnott Ian D R, Satsangi Jack
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK.
Inflamm Bowel Dis. 2008 Jun;14(6):756-62. doi: 10.1002/ibd.20405.
In the two benchmark controlled trials in Crohn's disease (CD) supporting its use, methotrexate (MTX) was used as the immunosuppressant of choice in immunomodulatory-naive patients. However, in daily clinical practice MTX is used generally after thiopurine analogs have failed.
The data are reported using intramuscular (IM) MTX (25 mg/week) in the induction of remission and oral MTX (15 mg/week) in 39 CD patients with a median age of 32 years, assessed retrospectively. In all, 97% patients had failed azathioprine and/or mercaptopurine therapy due to lack of efficacy in 14 (36%) and side effects in 24 (61%) patients; 21 patients (53%) were steroid-dependent with a median dose of 27.5 mg prednisolone/day for over a year.
In all, 72% of patients tolerated an induction regimen of 25 mg/week of IM MTX; 10% managed a reduced dose and 18% were intolerant. Remission was achieved in 71% of patients at 16 weeks. In the patients taking corticosteroids, withdrawal was achieved in 26% of patients and reduction in 47% at 16 weeks. Oral MTX therapy was continued in 22 patients after induction. In this group the probability of relapse was 78% at 50 weeks of oral therapy.
Parenteral MTX therapy is efficacious in inducing remission in steroid-dependent CD patients, although its use is limited by side effects in approximately 30% of patients. Low-dose oral therapy does not maintain long-term remission and is not a suitable alternative.
在两项支持使用甲氨蝶呤（MTX）治疗克罗恩病（CD）的基准对照试验中，MTX被用作免疫调节初治患者的首选免疫抑制剂。然而，在日常临床实践中，MTX通常在硫嘌呤类似物治疗失败后使用。
回顾性评估了39例年龄中位数为32岁的CD患者，报告了使用肌内注射（IM）MTX（25mg/周）诱导缓解和口服MTX（15mg/周）的数据。总体而言，97%的患者因疗效不佳（14例，36%）和副作用（24例，61%）而使硫唑嘌呤和/或巯嘌呤治疗失败；21例患者（53%）依赖类固醇，泼尼松龙中位剂量为27.5mg/天，持续超过一年。
总体而言，72%的患者耐受25mg/周的IM MTX诱导方案；10%的患者接受了减量治疗，18%的患者不耐受。16周时71%的患者实现缓解。在服用皮质类固醇的患者中，16周时26%的患者实现了撤药，47%的患者实现了减量。诱导后22例患者继续口服MTX治疗。在该组中，口服治疗50周时复发概率为78%。
肠外MTX治疗对诱导类固醇依赖的CD患者缓解有效，尽管约30%的患者因副作用限制了其使用。低剂量口服治疗不能维持长期缓解，不是合适的替代方案。
