Zink Angela, Strangfeld Anja, Schneider Matthias, Herzer Peter, Hierse Franka, Stoyanova-Scholz Maria, Wassenberg Siegfried, Kapelle Andreas, Listing Joachim
German Rheumatism Research Centre and Charité University Medicine, Berlin, Germany.
Arthritis Rheum. 2006 Nov;54(11):3399-407. doi: 10.1002/art.22193.
Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials.
Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria.
Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status.
RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.
随机临床试验（RCT）评估在由严格纳入标准定义的特定患者群体中治疗方法的疗效。这些试验在预测“现实世界”患者的治疗效果方面价值有限。这项观察性队列研究旨在通过根据类风湿关节炎（RA）患者符合主要试验的资格来评估肿瘤坏死因子（TNF）抑制剂的有效性，以补充RCT中获得的知识。
利用德国生物制剂登记处类风湿关节炎生物治疗观察（RABBIT[德语]）的数据，我们调查了接受TNF抑制剂（英夫利昔单抗、依那西普或阿达木单抗）治疗的RA患者中有多少符合导致这些药物获批的主要临床试验的资格。此外，使用美国风湿病学会20%（ACR20）和50%（ACR50）改善反应标准，对符合资格和不符合资格的患者的治疗效果进行了比较。
RABBIT登记处中只有21%-33%的患者符合主要试验的资格。在这些患者中，表明治疗效果的ACR20和ACR50改善反应与已发表试验中的反应率相当。在那些被认为不符合试验资格的患者中，ACR反应率较低；然而，绝对改善情况与符合资格的患者相似。不符合资格的患者基线疾病活动度较低、合并症较多且功能状态较低。
RCT队列仅反映了常规治疗中接受生物制剂治疗患者的一小部分。在临床环境中，生物制剂治疗的适应证与试验的纳入标准并不相同。尽管这些不符合主要试验纳入标准的长期、重度RA患者相对改善较小，但大多数此类患者仍将从生物治疗中获益。
