甲氨蝶呤在类风湿关节炎中的应用：二十五年的发展历程
Methotrexate in rheumatoid arthritis: a quarter century of development.
作者信息
Weinblatt Michael E
机构信息
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA.
出版信息
Trans Am Clin Climatol Assoc. 2013;124:16-25.
Abstract
Methotrexate (MTX) is now the most popular drug worldwide for the treatment of rheumatoid arthritis. Low-dose, weekly MTX (10 to 25 mg/wk) used as either monotherapy or in combination with other drugs has a superior efficacy profile as defined in placebo-controlled trials and comparable efficacy to other drugs including anti-TNF therapy. At 1 year, one third of patients on MTX have no radiographic progression and even greater effects are seen when combined with targeted biological therapies. MTX is well tolerated; gastrointestinal toxicity is the most common toxicity with rarely bone marrow, lung, or liver toxicity. MTX therapy has been a major advance in the treatment of rheumatoid arthritis and is now the cornerstone of therapy.
摘要
甲氨蝶呤（MTX）是目前全球治疗类风湿性关节炎最常用的药物。低剂量、每周一次的MTX（10至25毫克/周），无论是作为单一疗法还是与其他药物联合使用，在安慰剂对照试验中都具有卓越的疗效，并且与包括抗TNF治疗在内的其他药物疗效相当。在1年时，接受MTX治疗的患者中有三分之一没有影像学进展，与靶向生物疗法联合使用时效果更佳。MTX耐受性良好；胃肠道毒性是最常见的毒性，很少出现骨髓、肺部或肝脏毒性。MTX疗法是类风湿性关节炎治疗的一项重大进展，现在是治疗的基石。
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本文引用的文献
1
Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid.叶酸拮抗剂4-氨基蝶酰谷氨酸诱导儿童急性白血病的暂时缓解。
N Engl J Med. 1948 Jun 3;238(23):787-93. doi: 10.1056/NEJM194806032382301.
2
The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.PREMIER研究：一项多中心、随机、双盲临床试验，对比阿达木单抗联合甲氨蝶呤与单用甲氨蝶呤或单用阿达木单抗治疗早期侵袭性类风湿关节炎且既往未接受过甲氨蝶呤治疗的患者。
Arthritis Rheum. 2006 Jan;54(1):26-37. doi: 10.1002/art.21519.
3
Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.与单药治疗相比，依那西普与甲氨蝶呤联合治疗类风湿关节炎患者的疗效：双盲随机对照试验
Lancet. 2004 Feb 28;363(9410):675-81. doi: 10.1016/S0140-6736(04)15640-7.
4
Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis.组织反应性的治疗性抑制。II. 氨甲蝶呤对类风湿性关节炎和银屑病的作用。
Am J Med Sci. 1951 Feb;221(2):176-82.
5
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