Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Inflamm Bowel Dis. 2010 Aug;16(8):1421-30. doi: 10.1002/ibd.21246.
Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions.
We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included.
We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%-80% when the drug is applied by parenteral route in doses between 20-25 mg.
The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed.
低剂量甲氨蝶呤是一种广泛应用且有效的治疗方法，可用于治疗银屑病和类风湿关节炎等慢性炎症性疾病。前瞻性随机对照试验已经证明了甲氨蝶呤在克罗恩病（CD）中的疗效。我们对甲氨蝶呤治疗溃疡性结肠炎（UC）的疗效进行了系统评价，并在已知的甲氨蝶呤治疗炎症性肠病和其他炎症性疾病的药代动力学和不良反应的背景下讨论了结果。
我们在 Medline、Embase 和 Web of Science 上进行了系统的文献检索。所有描述用甲氨蝶呤治疗 UC 患者的出版物均被纳入。
我们确定了 12 项研究或回顾性病例系列研究和 5 项会议摘要符合纳入标准。只有 1 项研究报告了一项前瞻性随机安慰剂对照试验，使用的是 12.5 毫克的口服甲氨蝶呤，但没有显著的临床获益。然而，大多数未经控制的回顾性分析表明，当药物以 20-25 毫克的剂量通过静脉途径给药时，甲氨蝶呤治疗的临床反应率在 30%-80%之间。
唯一一项关于 UC 中使用甲氨蝶呤的随机对照试验采用了口服剂量，且剂量低于在 CD 中显示有效的剂量，并且没有显示出疗效，而使用与 CD 中相同剂量和给药途径的未经控制的回顾性研究则表明有获益。需要在 UC 中进行设计良好、前瞻性、安慰剂对照的甲氨蝶呤试验。
