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类风湿关节炎采用一线生物制剂或生物类似药治疗 6 个月:更新的系统评价和网络荟萃分析。

Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis.

机构信息

School of Health and Related Research (ScHARR),University of Sheffield,United Kingdom.

Department of Rheumatology,CHU de la Cavale-Blanche,Brest,France.

出版信息

Int J Technol Assess Health Care. 2019 Jan;35(1):36-44. doi: 10.1017/S0266462318003628. Epub 2019 Feb 6.

Abstract

OBJECTIVES

The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.

METHODS

Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.

RESULTS

Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.

CONCLUSIONS

In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.

摘要

目的

本研究旨在评估一线生物改善病情药物(boDMARDs)及其获批的生物类似物(bsDMARDs)相对于常规治疗(csDMARD)在达到 ACR(美国风湿病学会)和 EULAR(欧洲抗风湿病联盟)缓解方面的疗效。

方法

系统文献检索,检索了 8 个数据库截至 2017 年 1 月的随机对照试验(RCT)中关于 boDMARDs/bsDMARDs(联合 csDMARDs 或单药治疗)的 ACR 和 EULAR 数据。纳入了两类成年人群:甲氨蝶呤(MTX)初治的重度活动期类风湿关节炎患者;csDMARD 治疗经验丰富的中重度活动期类风湿关节炎患者。使用贝叶斯马尔可夫链蒙特卡罗模拟进行网络荟萃分析(NMA),采用随机效应模型和概率单位链接函数进行有序分类。

结果

46 项 RCT 符合纳入标准。在 MTX 初治的重度活动期 RA 人群中,没有符合纳入标准的生物类似物试验。MTX 加甲基强的松龙(MP)最有可能获得最佳 ACR 缓解。没有充分证据表明联合 boDMARD 优于强化(两种或更多)csDMARD。在 csDMARD 经验丰富的中重度 RA 人群中,对于 ACR 缓解的最大影响与托珠单抗(TCZ)单药治疗以及 bsDMARD 依那西普(ETN)SB4、boDMARD ETN 和 TCZ 的联合治疗相关。这些治疗方法对 EULAR 缓解的效果也最大。在 boDMARDs 和它们的 bsDMARDs 之间没有发现明显的差异。

结论

在 MTX 初治患者中,没有充分证据表明联合 boDMARD 优于两种或更多 csDMARD。在 csDMARD 经验丰富的患者中,boDMARDs 和 bsDMARDs 是可比的,所有联合 boDMARDs/bsDMARDs 都优于单一 csDMARD。

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