Estellat Candice, Ravaud Philippe
Département d'Epidémiologie et Recherche Clinique, Hôpital Bichat, Paris, France.
Arch Intern Med. 2012 Feb 13;172(3):237-44. doi: 10.1001/archinternmed.2011.1209.
One of the key elements of comparative treatment effectiveness research is head-to-head trials. We herein describe the control arms and the treatment received by patients in recently conducted or ongoing randomized controlled trials of biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis.
We identified all protocols recorded in ClinicalTrials.gov to October 1, 2009. We extracted trial length and funding, prior treatment, disease activity in eligible patients, and the treatment received in both trial arms.
Among the 91 trials identified (15 DMARD-naive trials, 63 biologic-naive trials, and 13 biologic-second-line trials) involving 18, 554 patients in control arms (3059, 13 095, and 2400 patients, respectively), only 5 compared biologic DMARDs head-to-head (2 of 7 noncommercially funded trials and 3 of 84 commercially funded trials). Two-thirds (66%) of these trials are ongoing. Networks of treatment comparisons reflect a predominant use of placebo as a comparator (81 of 102 comparisons among the 91 trials). In all 15 DMARD-naive trials, all control patients received a new treatment. In 54 of the 63 biologic-naive trials, 9224 of the 13, 095 control patients received their previously ineffective treatment, 3848 for more than 6 months, despite high levels of disease activity and contrary to guidelines. In biologic-second-line trials, 851 of the 2400 control patients received treatment comparable to their previously ineffective one.
Head-to-head trials of biologic DMARDs are still exceptions. Exposing patients in control arms who had a previous partial response or nonresponse to an inadequate treatment could lead to irreversible deterioration in condition.
对比治疗效果研究的关键要素之一是直接比较试验。我们在此描述近期开展的或正在进行的用于治疗类风湿关节炎的生物性改善病情抗风湿药（DMARDs）随机对照试验中，对照臂及患者接受的治疗情况。
我们确定了截至2009年10月1日在ClinicalTrials.gov上记录的所有方案。我们提取了试验时长、资金来源、既往治疗情况、符合条件患者的疾病活动度以及两个试验臂中患者接受的治疗。
在确定的91项试验中（15项初治DMARD试验、63项初治生物制剂试验和13项二线生物制剂试验），对照臂中有18554名患者（分别为3059名、13095名和2400名患者），只有5项试验对生物性DMARDs进行了直接比较（7项非商业资助试验中的2项以及84项商业资助试验中的3项）。这些试验中有三分之二（66%）仍在进行中。治疗比较网络显示，安慰剂作为对照的使用占主导（91项试验中的102次比较中有81次）。在所有15项初治DMARD试验中，所有对照患者均接受了新的治疗。在63项初治生物制剂试验中的54项试验里，13095名对照患者中有9224名接受了他们之前无效的治疗，其中3848名患者接受该治疗超过6个月，尽管疾病活动度很高且与指南相悖。在二线生物制剂试验中，2400名对照患者中有851名接受了与其之前无效治疗相当的治疗。
生物性DMARDs的直接比较试验仍然是少数情况。让对照臂中之前对不充分治疗有部分反应或无反应的患者暴露于此类治疗可能会导致病情不可逆转的恶化。
