Abstract：
OBJECTIVE: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies.
RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%.
CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.
METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies.
RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%.
CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.
摘要：
目的：本系统评价了肿瘤坏死因子（TNF）抑制剂对系统性幼年特发性关节炎（JIA）患者的疗效和安全性。
方法：使用PubMed搜索研究，Embase,科克伦,Ichushi-Web,和临床试验注册(从2000年到2021年)。使用用于随机对照试验（RCT）的Cochrane风险2版和Minds制定临床实践指南的手册来评估偏倚的风险，一个在日本推广循证医学的项目，用于观察性研究。
结果：纳入1项RCT和22项观察性研究。在英夫利昔单抗的RCT中，美国风湿病儿科学会（ACRPedi）14周时30/50/70的反应为63.8%/50.0%/22.4%，相对风险为1.30（95％置信区间[CI]：0.94-1.79）/1.48（95％CI：0.95-2.29）/1.89（95％CI：0.81-4.40），分别。在观察性研究中,ACRPedi30/50/70对etanercept12个月的应答率分别为76.7%/64.7%/46.4%,分别。英夫利昔单抗治疗导致17％的患者发生过敏反应，23％的患者发生输液反应。巨噬细胞活化综合征的发病率,TNF抑制剂引起的严重感染和恶性肿瘤发生率为0%-4%。
结论：因此，尽管TNF抑制剂相对安全，这些药物不太可能优先用于全身性JIA患者,因为其疗效不足.进一步研究,特别是精心设计的RCT，对于确认TNF抑制剂用于全身性JIA的有效性和安全性是必要的。
方法：使用PubMed搜索研究，Embase,科克伦,Ichushi-Web,和临床试验注册(从2000年到2021年)。使用用于随机对照试验（RCT）的Cochrane风险2版和Minds制定临床实践指南的手册来评估偏倚的风险，一个在日本推广循证医学的项目，用于观察性研究。
结果：纳入1项RCT和22项观察性研究。在英夫利昔单抗的RCT中，美国风湿病儿科学会（ACRPedi）14周时30/50/70的反应为63.8%/50.0%/22.4%，相对风险为1.30（95％置信区间[CI]：0.94-1.79）/1.48（95％CI：0.95-2.29）/1.89（95％CI：0.81-4.40），分别。在观察性研究中,ACRPedi30/50/70对etanercept12个月的应答率分别为76.7%/64.7%/46.4%,分别。英夫利昔单抗治疗导致17％的患者发生过敏反应，23％的患者发生输液反应。巨噬细胞活化综合征的发病率,TNF抑制剂引起的严重感染和恶性肿瘤发生率为0%-4%。
结论：因此，尽管TNF抑制剂相对安全，这些药物不太可能优先用于全身性JIA患者,因为其疗效不足.进一步研究,特别是精心设计的RCT，对于确认TNF抑制剂用于全身性JIA的有效性和安全性是必要的。
