Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
PLoS One. 2012;7(1):e30275. doi: 10.1371/journal.pone.0030275. Epub 2012 Jan 17.
Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT).
A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.
Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.
No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.
五种肿瘤坏死因子（TNF）阻滞剂（英夫利昔单抗、依那西普、阿达木单抗、培塞利珠单抗和戈利木单抗）可用于治疗类风湿关节炎。仅有少数临床试验比较了一种 TNF 阻滞剂与另一种 TNF 阻滞剂。因此，需要进行系统评价以间接比较这些药物。我们的研究旨在评估 TNF 阻滞剂治疗类风湿关节炎（RA）的疗效和安全性，并通过结合纳入的随机临床试验（RCT）的结果间接比较目前所有五种可用的阻滞剂。
我们使用包括 MEDLINE、SCOPUS（包括 EMBASE）、Cochrane 图书馆和电子搜索警报在内的数据库进行了系统文献综述。仅选择报告 TNF 阻滞剂与安慰剂（联合或不联合甲氨蝶呤 [MTX]）治疗 RA 的双盲 RCT 文章。收集的数据包括患者、干预、对照、结局、研究方法和潜在偏倚来源的信息。
有 41 篇文章报告了 26 项 RCT，这些文章被纳入系统综述和荟萃分析。五项 RCT 研究了英夫利昔单抗，七项研究了依那西普，八项研究了阿达木单抗，三项研究了戈利木单抗，三项研究了培塞利珠单抗。在所有时间点，TNF 阻滞剂均比安慰剂更有效，但与 MTX 相当。TNF 阻滞剂和 MTX 联合治疗优于 MTX 或 TNF 阻滞剂单独治疗。增加剂量并不能提高疗效。与 MTX 或安慰剂相比，TNF 阻滞剂相对安全。
没有一种单一的药物在疗效上明显优于其他药物，但安全性分析结果表明，依那西普可能是最安全的替代药物。有趣的是，考虑到疗效和安全性方面的因素，MTX 的成本效益相当高。
