Schröder Oliver, Stein Jürgen
Second Department of Internal Medicine, Division of Gastroenterology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Am J Gastroenterol. 2003 Mar;98(3):530-7. doi: 10.1111/j.1572-0241.2003.07305.x.
Despite many recent advances, some notable limitations exist in the medical management of patients with inflammatory bowel disease. Glucocorticoids suppress active inflammation very effectively, but their long term use is associated with high rates of relapse and unacceptable toxicity. 6-Mercaptopurine and its prodrug azathioprine are effective in inducing and maintaining remission; however, a significant number of patients are resistant or intolerant to thiopurines. Low dose methotrexate, an anti-inflammatory drug, is a well established medication for rheumatoid arthritis and psoriasis. After an initial report in 1989, several clinical trials and analyses of clinical notes have examined the role of methotrexate in patients with ulcerative colitis and Crohn's disease. This review was conducted to summarize the current knowledge about the underlying basic anti-inflammatory mechanisms of methotrexate as well as the pharmacology and toxicology of this drug with particular emphasis on inflammatory bowel disease. It also critically evaluates all existing trials not only in the induction of remission but also in maintenance therapy. We conclude that low dose methotrexate is an effective and safe treatment in glucocorticoid-dependent and thiopurine intolerant patients with Crohn's disease but not ulcerative colitis. It remains to be seen whether low dose methotrexate may also be useful in long term maintenance therapy in patients with inflammatory bowel disease.
尽管近年来取得了许多进展，但炎症性肠病患者的药物治疗仍存在一些显著局限性。糖皮质激素能非常有效地抑制活动性炎症，但其长期使用与高复发率和不可接受的毒性相关。6-巯基嘌呤及其前药硫唑嘌呤在诱导和维持缓解方面有效；然而，相当一部分患者对硫嘌呤耐药或不耐受。低剂量甲氨蝶呤是一种抗炎药物，是治疗类风湿性关节炎和银屑病的常用药物。在1989年首次报道后，多项临床试验和临床记录分析研究了甲氨蝶呤在溃疡性结肠炎和克罗恩病患者中的作用。本综述旨在总结目前关于甲氨蝶呤潜在基本抗炎机制以及该药物药理学和毒理学的知识，特别强调炎症性肠病。它还严格评估了所有现有试验，不仅包括诱导缓解试验，还包括维持治疗试验。我们得出结论，低剂量甲氨蝶呤对依赖糖皮质激素且不耐受硫嘌呤的克罗恩病患者是一种有效且安全的治疗方法，但对溃疡性结肠炎无效。低剂量甲氨蝶呤在炎症性肠病患者的长期维持治疗中是否也有用，还有待观察。
