依那西普与甲氨蝶呤单药及联合用药治疗类风湿关节炎的比较：TEMPO研究的两年临床和影像学结果，一项双盲随机试验

Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial.

作者信息

van der Heijde Désirée, Klareskog Lars, Rodriguez-Valverde Vicente, Codreanu Catalin, Bolosiu Horatiu, Melo-Gomes Jose, Tornero-Molina Jesus, Wajdula Joseph, Pedersen Ronald, Fatenejad Saeed

机构信息

Department of Rheumatology, University Hospital, Maastricht, The Netherlands.

出版信息

Arthritis Rheum. 2006 Apr;54(4):1063-74. doi: 10.1002/art.21655.

DOI:10.1002/art.21655

PMID:16572441

Abstract

OBJECTIVE

To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed.

METHODS

Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals.

RESULTS

A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups.

CONCLUSION

Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.

摘要

目的

评估在既往使用除甲氨蝶呤（MTX）以外的改善病情抗风湿药治疗失败的类风湿关节炎（RA）患者中，联合使用和单独使用依那西普与甲氨蝶呤（MTX）的疗效（包括影像学改变）及安全性。

方法

RA患者以双盲方式接受依那西普（皮下注射25mg，每周两次）、口服MTX（每周剂量高达20mg）或依那西普加MTX联合治疗，为期两年。采用美国风湿病学会（ACR）标准和疾病活动评分（DAS）评估临床反应，采用末次观察结转（LOCF）的改良意向性分析方法，并在完成治疗的患者群体中进行评估。每年对手部、腕部和前足的X线片进行评分，评估骨侵蚀和关节间隙狭窄情况。

结果

686例患者中共有503例进入研究的第2年。在这2年中，接受联合治疗的患者退出研究的比例显著低于其他组（联合治疗组为29%，依那西普组为39%，MTX组为48%）。LOCF分析和完成治疗患者分析均得出相似结果。联合治疗组的美国风湿病学会20%改善（ACR20）、ACR50和ACR70反应以及缓解率（基于DAS<1.6）均显著高于单药治疗组（P<0.01）。同样，联合治疗组在残疾改善方面（基于健康评估问卷）也更显著（P<0.01）。联合治疗组的影像学进展显著低于单药治疗组（P<0.05）；此外，依那西普组的影像学进展显著低于MTX组（P<0.05）。联合治疗组连续第二年总体疾病进展为负，95%置信区间小于零。3个治疗组的不良事件相似。