抗肿瘤坏死因子治疗类风湿关节炎临床试验中患者特征的变化：对过去 16 年文献分析的结果。

OBJECTIVE

To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients.

METHODS

A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date.

RESULTS

44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score.

CONCLUSION

Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.

目的

评估肿瘤坏死因子 α（TNFα）抑制剂治疗类风湿关节炎（RA）患者的随机对照研究中基线患者特征和入组标准的变化。

方法

采用预设的纳入标准，进行系统文献复习，以确定评估 TNFα 抑制剂在成年 RA 患者中的随机、双盲、对照试验。评估了甲氨蝶呤经验和甲氨蝶呤初治研究人群的入组标准和基线临床特征。每个试验的入组开始日期作为时间指标。锚定时间是最早可识别的入组日期的研究。

结果

1993 年至 2008 年期间，有 44 篇主要出版物（报告主要研究终点）符合纳入标准。1993 年 8 月和 1997 年 5 月被确定为 37 项甲氨蝶呤经验研究和 7 项甲氨蝶呤初治研究的时间锚点。在甲氨蝶呤经验试验中，在所包括的年份中，任何纳入标准（包括肿胀关节计数和 C 反应蛋白（CRP））均未观察到显著变化，但基线肿胀关节计数、CRP 和总 Sharp 或 van der Heijde 改良 Sharp 评分随时间显著下降，但基线触痛关节计数没有下降。在甲氨蝶呤初治研究中，肿胀关节和触痛关节纳入标准随时间显著下降，但基线触痛关节计数、基线 CRP、CRP 纳入标准或基线总 Sharp 或 van der Heijde 改良 Sharp 评分没有下降。