Département de Rhumatologie, Hôpital Lapeyronie, 371 avenue du Doyen G. Giraud, Montpellier cedex 5, France.
J Rheumatol. 2011 May;38(5):835-45. doi: 10.3899/jrheum.100665. Epub 2011 Jan 15.
To compare the clinical efficacy of certolizumab pegol (CZP) with that of other anticytokine agents indicated for the treatment of rheumatoid arthritis (RA) with identical therapeutic indication (anti-tumor necrosis factor-α, anti-interleukin 1 or 6), with the objective of determining the noninferiority of CZP.
A systematic review was performed to identify randomized controlled trials that assessed the efficacy of anticytokine agents in combination with conventional disease-modifying antirheumatic drugs (DMARD) after 6 months of treatment, using the American College of Rheumatology (ACR) response criteria, in patients with RA who have shown inadequate response to DMARD including methotrexate. Indirect treatment comparisons were carried out by a multiple-treatment Bayesian random-effects metaanalysis. Data were analyzed using the Markov chain Monte Carlo simulation. Noninferiority of CZP was assessed in comparison with a predefined equivalence margin of 5%.
Nineteen placebo-controlled studies were identified: 14 evaluated the efficacy of 5 anti-TNF-α agents (infliximab, etanercept, adalimumab, golimumab, CZP) and 5 evaluated efficacy of 2 anti-interleukin agents (anakinra, tocilizumab). Every treatment showed significant efficacy versus placebo in individual studies. The multiple-treatment metaanalysis showed a highest OR for CZP on ACR20 response. Metaanalysis indicates that the efficacy of CZP according to ACR20 response is superior to that of infliximab, adalimumab, and anakinra, and equivalent or superior to that of etanercept, golimumab, and tocilizumab. According to ACR50 response, the efficacy of CZP is equivalent or superior to that of all other anticytokines.
Results of this original multiple-treatment Bayesian metaanalysis indicate that certolizumab pegol is at least as efficacious as the preexisting antirheumatic anticytokine biotherapies.
比较培塞利珠单抗(CZP)与其他具有相同治疗适应证(抗肿瘤坏死因子-α、抗白细胞介素 1 或 6)的抗细胞因子药物在治疗类风湿关节炎(RA)方面的临床疗效,旨在确定 CZP 的非劣效性。
系统检索评估抗细胞因子药物与常规改善病情抗风湿药物(DMARD)联合使用 6 个月后,根据美国风湿病学会(ACR)缓解标准,在对包括甲氨蝶呤在内的 DMARD 反应不足的 RA 患者中的疗效的随机对照试验,采用多治疗贝叶斯随机效应荟萃分析进行间接治疗比较。使用马尔可夫链蒙特卡罗模拟进行数据分析。采用与预先设定的 5%等效性边界进行比较,评估 CZP 的非劣效性。
共确定了 19 项安慰剂对照研究:14 项评估了 5 种抗 TNF-α 药物(英夫利昔单抗、依那西普、阿达木单抗、戈利木单抗、CZP)的疗效,5 项评估了 2 种抗白细胞介素药物(阿那白滞素、托珠单抗)的疗效。在各项研究中,每种治疗均显示出与安慰剂相比具有显著疗效。多治疗荟萃分析显示,CZP 在 ACR20 反应方面的 OR 最高。Meta 分析表明,根据 ACR20 反应,CZP 的疗效优于英夫利昔单抗、阿达木单抗和阿那白滞素,且与依那西普、戈利木单抗和托珠单抗相当或优于后者。根据 ACR50 反应,CZP 的疗效与所有其他抗细胞因子药物相当或优于后者。
本原始多治疗贝叶斯荟萃分析结果表明,培塞利珠单抗至少与现有的抗风湿抗细胞因子生物疗法同样有效。