Emery Paul, Breedveld Ferdinand, van der Heijde Désirée, Ferraccioli Gianfranco, Dougados Maxime, Robertson Deborah, Pedersen Ronald, Koenig Andrew S, Freundlich Bruce
University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, [corrected] Leeds, UK.
Arthritis Rheum. 2010 Mar;62(3):674-82. doi: 10.1002/art.27268.
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.
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.
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.
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.
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。
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）。
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。
早期持续的依那西普 - MTX联合治疗始终优于MTX单药治疗。联合治疗在2年的研究期间带来了重要的临床和影像学益处，且无显著额外安全风险。
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