A mixed treatment comparison of the short-term efficacy of biologic disease modifying anti-rheumatic drugs in established rheumatoid arthritis.

Source

Centre for Applied Health Economics, School of Medicine, Griffith Health Institute, Griffith University , Australia.

Abstract

Abstract Background: The short-term efficacy of biological disease modifying anti-rheumatic drugs (bDMARDs) for the treatment of established moderate to severe rheumatoid arthritis (RA) has been demonstrated by various randomized placebo or active treatment controlled trials. However, there is a lack of direct comparison of these agents. Scope: To compare the short-term efficacy of nine bDMARDs - abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab - in patients with established RA. Findings: A systematic review was conducted to obtain all available efficacy data for each included bDMARD. Medline, EMBASE, and Cochrane clinical trials were searched for trials in patients with RA. Twenty-seven trials were retrieved from a systematic literature search and included in the meta-analysis. Mixed treatment comparison (MTC) techniques were used to perform indirect comparisons. Analyses were conducted to estimate the odds ratio of an ACR20, ACR50, and ACR70 response at approximately six months if treated with a bDMARD compared with placebo or methotrexate. Between-drug comparisons were also made. The analyses were performed including recommended doses only (as per the product information). All drugs except anakinra and golimumab demonstrated a statistically significant advantage compared to control treatment for ACR20 responses. The between-drug comparisons revealed a statistically significant advantage for certolizumab compared to most bDMARDs for ACR20, ACR50 and ACR70 response and for etanercept versus adalimumab and anakinra for ACR20 and ACR50 response, as well as a statistically significant advantage for tocilizumab versus anakinra for ACR50 response. Conclusion: The analyses, using MTC of efficacy of nine bDMARDs suggest that treatment with anakinra is inferior to other bDMARDs and that etanercept and certolizumab may be more effective than other bDMARDs. There are some limitations of our analyses due to MTC assumptions, variations in trial design and the fact that only ACR outcomes at six months were included.

PMID: 21848493

间接比较九种生物DMARDs治疗长病程RA的短期疗效

Turkstra E, et al. Curr Med Res Opin. 2011 Aug 18. 提前在线.

背景: 生物学DMARDs对于中重度长病程类风湿关节炎(RA)患者的短期疗效已通过各种随机、安慰剂对照或有效药物对照的临床试验得到证实。然而，尚无直接比较这些生物制剂的临床试验。

研究对象: 比较九种生物DMARDs治疗长病程RA的短期疗效，包括阿贝西普(abatacept)、阿达木(adalimumab)、阿那白滞素(anakinra)、舍妥利珠(certolizumab)、依那西普(etanercept)、戈利木(golimumab)、英夫利昔(infliximab)、利妥昔(rituximab)以及妥昔丽珠(tocilizumab)。

发现: 进行一项系统性评价，以获得每种生物DMARD的可获得的疗效数据。检索了Medline、EMBASE和考科蓝临床试验数据库，获取所有涉及RA的临床试验资料。共搜寻到27个临床试验并纳入荟萃分析。混合治疗比较(mixed treatment comparison, MTC)技术用于这项间接比较研究。通过分析得到各种生物DMARD较MTX/安慰剂治疗6个月时达到ACR20、ACR50和ACR70疗效的比值比(OR)。同时也做了不同生物制剂之间的比较。仅纳入使用说明书推荐剂量的临床试验。除了阿那白滞素和戈利木，其它药物均较对照获得显著更高的ACR20达标率。生物制剂之间的比较提示舍妥利珠较其它大多数生物DMARDs有更高的ACR20、ACR50及ACR70达标率，依那西普较阿达木和阿那白滞素有更高的ACR20和ACR50达标率，妥昔丽珠较阿那白滞素有更高的ACR50应答率。

结论: 利用MTC分析比较了九种生物DMARDs治疗RA的疗效，结果提示阿那白滞素是疗效最弱的生物DMARDs，依那西普和舍妥利珠比其它生物DMARDs更有效。鉴于MTC分析所需的一些假设，本研究有一些局限性。例如不同试验设计之间的差异，以及只有6个月的ACR疗效数据纳入分析等。