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非生物制剂DMARs联合治疗类风湿性关节炎的随机临床试验

Authors
Peter H Schur, MD
James R O'Dell, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD
Translators
毛志国, 副主任医师，副教授

引言

目前，可用于改变病情的传统抗风湿药物(disease modifying antirheumatic drug, DMARD)以及生物制剂已逾十数种，分别称为非生物DMARD和生物DMARD；因此，两种药物的可能联合方案超过100种，而3种药物的联合方案则超过1000种。其中，只有少数几种方案已在随机临床试验中进行过直接比较。一些精心设计的研究已证实，某些药物组合既有显著的临床疗效又有能被普遍接受的毒性风险。

针对不同的非生物DMARD组合治疗早期、确诊的类风湿性关节炎(rheumatoid arthritis, RA)的代表性临床试验将总结在此。RA的一般治疗方法和针对其生物制剂的随机对照试验将单独讨论。 (参见“成人类风湿关节炎治疗的一般原则”和“肿瘤坏死因子抑制剂应用于类风湿关节炎的随机临床试验”和“应用利妥昔单抗和其他B细胞靶向疗法治疗类风湿关节炎”和“类风湿关节炎的T细胞靶向治疗”和“抑制IL-1、IL-6和RANKL的生物制剂治疗类风湿关节炎的随机临床试验”)

以甲氨蝶呤为基础的联合方案

金制剂和MTX — 一项研究很好地阐明了在使用甲氨喋呤(methotrexate, MTX)期间加用金制剂肌内注射联合治疗的临床功效，该研究纳入了65例对MTX(平均剂量为每周18.5mg)有部分反应的RA患者，这些患者在继续接受MTX治疗的同时，被随机分配至加用硫葡萄糖金钠(起始剂量为10mg，之后第1周为25mg，再以后每周为50mg)或安慰剂，均持续48周[1]。试验结束时，金制剂注射组的结果显著优于安慰剂组：

  • 金制剂加MTX治疗组的患者达到美国风湿病学会(American College of Rheumatology, ACR)20%改善标准(即ACR20)的应答率显著更高(61% vs 30%)。
  • 接受了金制剂的受试者中达到ACR50应答的比例也更高(26% vs 4%)。
  • ACR70应答则仅见于接受了金制剂的患者(21% vs 0%)。
  • 金制剂加MTX治疗组中因缺乏疗效而停药的人数比安慰剂组更少(分别为3/9 vs 10/14)。
  • 金制剂加MTX组中因不良反应而停药的人数比例并没有显著增加(10% vs 3%)。

38例接受金制剂/MTX治疗的患者中，17例出现了黏膜皮肤副作用，这导致其暂停金制剂治疗。然而，这17例患者中有15例重新使用了金制剂(重新使用时的剂量为导致黏膜皮肤不良反应时剂量的一半，此后以每周5mg的剂量逐渐增加，至最大可耐受剂量或每周50mg)且没有复发皮疹或黏膜炎。

            

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Literature review current through: 2017-06 . | This topic last updated: 2016-12-01.
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