Program of Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada.
Semin Arthritis Rheum. 2013 Jun;42(6):597-618. doi: 10.1016/j.semarthrit.2012.10.006. Epub 2013 Jan 18.
To systematically review the clinical efficacy and safety evidence of biologic drugs used to treat the polyarticular category of juvenile idiopathic arthritis (JIA).
The literature was searched between 2000 and September 2012 for randomized controlled trials (RCTs), non-randomized comparative studies, and non-comparative observational cohort studies. The drugs evaluated included etanercept, infliximab, adalimumab, abatacept, anakinra, and ritixumab. Eligible studies included 20 or more patients with JIA, the majority of whom had polyarticular course disease. Outcomes of interest were disease improvement defined by the American College of Rheumatology criteria for Pediatrics, disease flares, rates of inactive disease, remissions, discontinuations, and adverse events (severe and non-severe).
Thirty-seven studies were included, the majority focused on etanercept. Seven RCTs were identified, including one each for etanercept, infliximab, adalimumab, abatacept, and anakinra, and one each looking at etanercept or infliximab as first-line therapies. There was strong evidence to support the efficacy and safety of biologics over the short-term, but a lack of long-term data for treatments other than etanercept. Several high-quality patient registries confirmed the efficacy and safety of etanercept over the long-term.
Current evidence shows that a short-term improvement in treatment response is achieved when patients with polyarticular JIA with an inadequate response to conventional treatment are treated with biologics. Long-term effectiveness data, however, are sparse leaving many questions regarding switches between biologics, handling patients that achieve disease remission, and long-term safety. Study designs other than RCTs may be important in understanding the role of biologics in JIA over the long-term.
系统评价生物制剂治疗幼年特发性关节炎（JIA）多关节型的临床疗效和安全性证据。
检索了 2000 年至 2012 年 9 月的随机对照试验（RCT）、非随机对照研究和非对照观察队列研究的文献。评估的药物包括依那西普、英夫利昔单抗、阿达木单抗、阿巴西普、阿那白滞素和利妥昔单抗。合格的研究包括 20 例或更多的 JIA 患者，其中大多数患者为多关节型疾病。感兴趣的结局是美国风湿病学会儿科标准定义的疾病改善、疾病发作、无疾病发生率、缓解、停药和不良事件（严重和非严重）。
共纳入 37 项研究，其中大部分集中在依那西普。确定了 7 项 RCT，包括依那西普、英夫利昔单抗、阿达木单抗、阿巴西普和阿那白滞素各 1 项，以及 1 项评估依那西普或英夫利昔单抗作为一线治疗的研究。有强有力的证据支持生物制剂在短期治疗中的疗效和安全性，但除依那西普以外的治疗方法缺乏长期数据。几个高质量的患者登记处证实了依那西普在长期治疗中的疗效和安全性。
目前的证据表明，对于常规治疗反应不足的多关节型 JIA 患者，用生物制剂治疗可在短期内改善治疗反应。然而，长期有效性数据很少，这使得关于生物制剂之间的转换、处理达到疾病缓解的患者以及长期安全性等问题存在很多疑问。除 RCT 以外的研究设计可能对于理解生物制剂在 JIA 中的长期作用很重要。
