The PREMIER study - A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment
The PREMIER study - A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment
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DOI：
10.1002/art.21519
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Spencer-Green, GT
中科院分区：
文献类型：
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作者：
Breedveld, FC;Weisman, MH;Spencer-Green, GT
Objective.比较阿达木单抗联合甲氨蝶呤（MTX）与MTX单药治疗或阿达木单抗单药治疗早期侵袭性类风湿关节炎（RA）患者的疗效和安全性。这是一项为期2年的多中心、双盲、活性对照药物对照研究，纳入了799例活动性疾病持续时间< 3年且从未接受过MTX治疗的RA患者。治疗包括阿达木单抗40 mg皮下注射，每隔一周一次+口服MTX，阿达木单抗40 mg皮下注射，每隔一周一次，或每周一次口服MTX。第一年的共同主要终点是美国流变学学会50%改善（ACR 50）和改良总Sharp评分较基线的平均变化。联合治疗上级MTX和阿达木单抗单药治疗的所有测量结果。在第1年，接受联合治疗的患者（62%）比接受MTX或阿达木单抗单药治疗的患者（分别为46%和41%;均P < 0.001）表现出更多的ACR 50应答。在第1年和第2年的ACR 20、ACR 70和ACR 90缓解率中观察到联合治疗的相似优效性。联合治疗组患者在第1年和第2年的放射学进展（分别为1.3和1.9夏普单位）显著低于MTX组（5.7和10.4夏普单位）或阿达木单抗组（3.0和5.5夏普单位）。治疗2年后，49%接受联合治疗的患者显示疾病缓解（28关节疾病活动评分< 2.6），49%显示主要临床应答（ACR 70应答至少连续6个月），比率约为接受任一单药治疗患者的两倍。3组不良事件发生率相似。在该早期侵袭性RA患者人群中，阿达木单抗联合MTX治疗在改善疾病体征和症状、抑制放射学进展和实现临床缓解方面显著上级MTX单药治疗或阿达木单抗单药治疗。
Objective. To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.Methods. This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year I were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score.Results. Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at I and 2 years. There was significantly less radiographic progression (P < 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score < 2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups.Conclusion. In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.