Comparative Efficacy of JAK Inhibitors for Moderate-To-Severe Rheumatoid Arthritis: A Network Meta-Analysis
Comparative Efficacy of JAK Inhibitors for Moderate-To-Severe Rheumatoid Arthritis: A Network Meta-Analysis
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DOI：
10.1007/s12325-020-01303-3
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发表时间：
2020-04-15
影响因子：
3.8
通讯作者：
Betts, Keith A.
中科院分区：
文献类型：
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作者：
Pope, Janet;Sawant, Ruta;Betts, Keith A.
Janus激酶（JAK）抑制剂是一类治疗类风湿关节炎（RA）的靶向药物，具有良好的临床疗效。然而，很少有人知道它们的功效相互比较。该网络荟萃分析（NMA）估计了目前批准用于RA的JAK抑制剂的比较疗效。方法对3项已获批准的JAK抑制剂（托法替尼、巴瑞替尼和upadacitinib）单药或联合治疗常规合成抗风湿药物（csDMARD-IR）疗效不佳的中重度RA患者的III期随机对照试验（RCT）进行有针对性的文献综述。使用Bayesian NMA，在12周和24周分别评估美国流变学学会（ACR）20/50/70应答和临床缓解（定义为DAS 28-CRP < 2.6）。结果11项随机对照试验被纳入NMA。所有JAK抑制剂均表现出显著优于csDMARD的疗效。在联合治疗中，upadacitinib 15 mg的12周ACR 50缓解率最高（中位数[95%可信区间]：43.4% [33.4%，54.5%]），其次是托法替布5 mg（38.7%，[28.6%，49.8%]）、巴瑞替尼2 mg（37.1%，[25.0%，50.6%]）和巴瑞替尼4 mg（36.7%，[27.2%，47.0%]）。对于ACR 20/70和第24周也观察到类似的结果。在第12周，还发现Upadacitinib 15 mg + csDMARD的临床缓解率最高（29.8% [16.9%，47.0%]），其次是托法替布5 mg（24.3%，[12.7%，40.2%]）、巴瑞替尼4 mg（22.8%，[11.8%，37.5%]）和巴瑞替尼2 mg（20.1%，[8.6%，37.4%]）。在第24周观察到类似结果。在单药治疗中，upadacitinib的ACR 50应答率（38.5% [25.3%，53.2%]）高于托法替尼（30.4% [18.3%，45.5%]）。JAK抑制剂之间的疗效指标差异无统计学意义。结论NMA发现，在批准的JAK联合治疗和单药治疗csDMARD-IR RA患者中，upadacitinib 15 mg每日一次在ACR应答和临床缓解方面具有数值上更高的疗效。
Introduction Janus kinase (JAK) inhibitors are a class of targeted therapies for rheumatoid arthritis (RA) with established clinical efficacy. However, little is known about their efficacy compared with each other. This network meta-analysis (NMA) estimated the comparative efficacy of JAK inhibitors currently approved for RA. Methods A targeted literature review was conducted for phase III randomized controlled trials (RCTs) evaluating the efficacy of three approved JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) as monotherapy or combination therapy among patients with moderate-to-severe RA who had inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR). Using Bayesian NMA, American College of Rheumatology (ACR) 20/50/70 responses and clinical remission (defined as DAS28-CRP < 2.6) were evaluated separately at 12 and 24 weeks. Results Eleven RCTs were identified and included in the NMA. All JAK inhibitors demonstrated significantly better efficacy than csDMARD. Among combination therapies, upadacitinib 15 mg had the highest 12-week ACR50 responses (median [95% credible interval]: 43.4% [33.4%, 54.5%]), followed by tofacitinib 5 mg (38.7% [28.6%, 49.8%]), baricitinib 2 mg (37.1% [25.0%, 50.6%]), and baricitinib 4 mg (36.7%, [27.2%, 47.0%]). Similar results were observed for ACR20/70 and at week 24. Upadacitinib 15 mg + csDMARD was also found to have the highest clinical remission rates at week 12 (29.8% [16.9%, 47.0%]), followed by tofacitinib 5 mg (24.3%, [12.7%, 40.2%]), baricitinib 4 mg (22.8%, [11.8%, 37.5%]), and baricitinib 2 mg (20.1%, [8.6%, 37.4%]). Similar results were seen at week 24. Among monotherapies, upadacitinib had a higher ACR50 response (38.5% [25.3%, 53.2%]) than tofacitinib (30.4% [18.3%, 45.5%]). The differences in efficacy measures were not statistically significant between the JAK inhibitors. Conclusions The NMA found that upadacitinib 15 mg once daily had numerically higher efficacy in terms of ACR response and clinical remission among approved JAK combination therapies and monotherapies for csDMARD-IR patients with RA.