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托珠单抗、利妥昔单抗、阿巴西普和托法替布在对肿瘤坏死因子抑制剂反应不足的活动性类风湿关节炎患者中的疗效和安全性比较:一项随机对照试验的贝叶斯网络荟萃分析。

Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.

作者信息

Lee Young Ho, Bae Sang-Cheol

机构信息

Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

出版信息

Int J Rheum Dis. 2016 Nov;19(11):1103-1111. doi: 10.1111/1756-185X.12822. Epub 2015 Dec 22.

Abstract

AIMS

This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors.

METHODS

We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors.

RESULTS

Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options.

CONCLUSIONS

Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events.

摘要

目的

本研究旨在评估生物制剂和托法替布在对肿瘤坏死因子(TNF)抑制剂反应不足的类风湿关节炎(RA)患者中的相对疗效和安全性。

方法

我们进行了一项贝叶斯网络荟萃分析,以整合来自随机对照试验(RCT)的直接和间接证据,这些试验考察了托珠单抗、利妥昔单抗、阿巴西普和托法替布在对TNF抑制剂反应不足的RA患者中的疗效和安全性。

结果

四项纳入1796例患者的RCT符合纳入标准。托珠单抗8mg组的美国风湿病学会20%(ACR20)反应率显著高于阿巴西普组和托法替布组。基于累积排名曲线下面积(SUCRA)的排名概率表明,托珠单抗8mg在实现ACR20反应率方面成为最佳治疗的概率最高(SUCRA = 0.9863),其次是利妥昔单抗(SUCRA = 0.6623)、阿巴西普(SUCRA = 0.5428)、托珠单抗4mg(SUCRA = 0.4956)、托法替布10mg(SUCRA = 0.4715)、托法替布5mg(SUCRA = 0.3415)和安慰剂(SUCRA = 0)。相比之下,基于不良事件导致的撤药数量的安全性在各治疗方案之间无显著差异。

结论

对于对TNF治疗反应不足的RA患者,托珠单抗8mg是基于ACR20反应率具有早期良好反应且安全性可接受的二线非TNF生物制剂,其次是利妥昔单抗、阿巴西普和托法替布,并且这些治疗均未伴有因不良事件导致撤药的显著风险。

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