依那西普联合甲氨蝶呤疗法与单一疗法治疗早期类风湿关节炎的两年临床和影像学结果：一项为期两年的双盲随机研究

Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study.

作者信息

Emery Paul, Breedveld Ferdinand, van der Heijde Désirée, Ferraccioli Gianfranco, Dougados Maxime, Robertson Deborah, Pedersen Ronald, Koenig Andrew S, Freundlich Bruce

机构信息

University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, [corrected] Leeds, UK.

出版信息

Arthritis Rheum. 2010 Mar;62(3):674-82. doi: 10.1002/art.27268.

DOI:10.1002/art.27268

PMID:20187135

Abstract

OBJECTIVE

To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis.

METHODS

Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score < or = 0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission.

RESULTS

At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen.

CONCLUSION

Early sustained combination etanercept-MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk.

摘要

目的

评估初始的1年依那西普 - 甲氨蝶呤（MTX）联合治疗及MTX单药治疗方案的延续和变更如何影响早期、活动期类风湿关节炎的长期缓解及影像学进展。

方法

受试者在基线时被随机分组，为期2年；完成1年联合治疗或MTX单药治疗的患者进入第2年。原联合治疗组在第2年继续联合治疗（依那西普/依那西普组；n = 111）或接受依那西普单药治疗（依那西普/依组；n = 111）；原MTX单药治疗组在第2年接受联合治疗（甲氨蝶呤/依那西普组；n = 90）或继续单药治疗（甲氨蝶呤/甲氨蝶呤组；n = 99）。疗效终点包括第2年时的缓解（28个关节疾病活动评分[DAS28]<2.6）和影像学无进展（改良Sharp/van der Heijde评分变化≤0.5）。对改良意向性治疗人群（n = 398）进行末次观察结转分析，并对缓解情况进行事后无反应者插补（NRI）分析（n = 528）。

结果

在第2年时，依那西普/依那西普组、依那西普/依组、甲氨蝶呤/依那西普组和甲氨蝶呤/甲氨蝶呤组分别有62/108、54/108、51/88和33/94例受试者达到DAS28缓解（依那西普/依那西普组和甲氨蝶呤/依那西普组与甲氨蝶呤/甲氨蝶呤组相比，P<0.01）。一项更保守的事后2年NRI分析证实了这一效果，在相同的各相应组中，分别有59/131、50/134、48/133和29/130例达到缓解（依那西普/依那西普组、依那西普/依组和甲氨蝶呤/依那西普组与甲氨蝶呤/甲氨蝶呤组相比，每组P<0.05）。达到影像学无进展（n = 360）的受试者比例在依那西普/依那西普组（与其他各组相比，P<0.01）、依那西普/依组、甲氨蝶呤/依那西普组和甲氨蝶呤/甲氨蝶呤组分别为89/99、74/99、59/79和56/83。未发现新的安全信号或严重不良事件的组间差异。