Tarp Simon, Amarilyo Gil, Foeldvari Ivan, Christensen Robin, Woo Jennifer M P, Cohen Neta, Pope Tracy D, Furst Daniel E
Musculoskeletal Statistics Unit, Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Rheumatology (Oxford). 2016 Apr;55(4):669-79. doi: 10.1093/rheumatology/kev382. Epub 2015 Nov 30.
To define the optimal biologic agent for systemic JIA (sJIA) based on safety and efficacy data from a randomized controlled trial (RCT).
Through a systematic literature search, sJIA RCTs evaluating biologic agents were identified. The primary efficacy outcome was defined as a 30% improvement according to the modified American College of Rheumatology Paediatric 30 response criteria (JIA ACR30). The primary safety outcome was defined as serious adverse events (SAEs). Outcomes were analysed by pairwise and network meta-analyses. The quality of evidence between biologic agents was assessed by applying the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
From the 493 citations originally identified, 5 RCTs were eligible for inclusion-one each for anakinra, canakinumab and tocilizumab and two for rilonacept: all vs placebo. While all were effective, the network meta-analysis indicated with low-quality evidence (due to indirect comparison and inconsistency) that rilonacept-treated patients were less likely to respond than those treated with canakinumab [odds ratio (OR) 0.10 (95% CI 0.02, 0.38), P = 0.001] or tocilizumab [OR 0.12 (95% CI 0.03, 0.44), P = 0.001]. Risks of SAEs were similar among the biologic agents (supported by very low-quality evidence) and not different from placebo.
Despite heterogeneous eligibility criteria and study designs across the five studies and different modified JIA ACR30 criteria, this meta-analysis of short-term RCTs presents empirical evidence that canakinumab and tocilizumab are more effective than rilonacept. Biologic agents in sJIA seem safe and comparable with respect to SAE risk in the short term.
基于一项随机对照试验（RCT）的安全性和有效性数据，确定用于全身型幼年特发性关节炎（sJIA）的最佳生物制剂。
通过系统的文献检索，识别评估生物制剂的sJIA RCT。主要疗效结局根据改良的美国风湿病学会儿科30反应标准（JIA ACR30）定义为改善30%。主要安全性结局定义为严重不良事件（SAE）。通过成对和网状荟萃分析对结局进行分析。采用推荐分级评估、制定和评价（GRADE）方法评估生物制剂之间证据的质量。
从最初识别的493篇文献中，5项RCT符合纳入标准——阿那白滞素、卡那单抗和托珠单抗各1项，利罗那肽2项：均与安慰剂对照。虽然所有药物均有效，但网状荟萃分析显示，证据质量低（由于间接比较和不一致性），利罗那肽治疗的患者比卡那单抗治疗的患者反应可能性小[比值比（OR）0.10（95%CI 0.02，0.38），P = 0.001]，也比托珠单抗治疗的患者反应可能性小[OR 0.12（95%CI 0.03，0.44），P = 0.001]。生物制剂之间SAE的风险相似（证据质量极低），与安慰剂无差异。
尽管五项研究的纳入标准和研究设计存在异质性，且改良的JIA ACR30标准不同，但这项对短期RCT的荟萃分析提供了经验证据，表明卡那单抗和托珠单抗比利罗那肽更有效。sJIA中的生物制剂在短期内似乎安全，且SAE风险相当。
