德国卫生保健质量与效率研究所Beate Wieseler小组比较了不同生物药物治疗类风湿关节炎的疗效。2020年7月7日出版的《英国医学杂志》发表了该成果。

为了评估生物药物在足够相似的患者人群中治疗类风湿关节炎，基于当前关键结局定义的相对有效性，研究组使用临床赞助商提供的临床研究报告和类风湿关节炎关键结局数据，汇总从建库到2017年2月的相关数据，重新分析，筛选出标准甲氨蝶呤治疗失败至少24周后，采用生物药物联合甲氨蝶呤治疗类风湿关节炎成人患者的随机对照试验，并进行系统回顾和网络荟萃分析。

最终共确定了45项合格试验。结合来自临床研究报告的数据和对单个患者数据再分析的汇总结果，研究组进行了广泛的分析，得到足够相似的人群和网络荟萃分析的同质研究结果，包括多达35项关于8种生物药物与甲氨蝶呤联合治疗的研究。

这些分析表明，联合治疗之间的统计学差异很小。例如，就临床缓解或疾病活动度低（临床疾病活动指数分别≤2.8或≤10）而言，anakinra与其他七种生物药物相比，临床获益更低；就严重不良反应或感染而言，certolizumab聚乙二醇与其他七种生物药物相比，显示出更大的危害。

某些结果的95%置信区间非常宽，暗示这八种生物药物之间存在不确定性差异，但对于疾病活动低、严重不良事件和感染来说，宽95%置信区间并不那么显著。由于缺乏针对性试验，结果主要是基于有限数量研究的间接比较，不能包括最近批准的Janus激酶抑制剂。

总之，对甲氨蝶呤治疗失败后的类风湿关节炎患者，不同生物药物联合甲氨蝶呤治疗之间的利弊差异很小。但由于缺乏长期直接比较，该分析存在一定缺陷。

附：英文原文

Title: Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data

Author: Kirsten Janke, Katharina Biester, Dietmar Krause, Bernd Richter, Christoph Schürmann, Katharina Hirsch, Helmut Hrn, Michaela Florina Kerekes, Petra Kohlepp, Beate Wieseler

Issue&Volume: 2020/07/07

Abstract: Objective To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes.

Design Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data.

Data sources Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017.

Eligibility criteria for selecting studies Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks.

Results 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included.

Conclusions For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.

DOI: 10.1136/bmj.m2288

Source: https://www.bmj.com/content/370/bmj.m2288