Tocilizumab Inhibits Structural Joint Damage in Rheumatoid Arthritis Patients With Inadequate Responses to Methotrexate Results From the Double-Blind Treatment Phase of a Randomized Placebo-Controlled Trial of Tocilizumab Safety and Prevention of Structural Joint Damage at One Year
Tocilizumab Inhibits Structural Joint Damage in Rheumatoid Arthritis Patients With Inadequate Responses to Methotrexate Results From the Double-Blind Treatment Phase of a Randomized Placebo-Controlled Trial of Tocilizumab Safety and Prevention of Structural Joint Damage at One Year
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DOI：
10.1002/art.30158
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发表时间：
2011-03-01
影响因子：
--
通讯作者：
Fleischmann, Roy
中科院分区：
文献类型：
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作者：
Kremer, Joel M.;Blanco, Ricardo;Fleischmann, Roy
Objective.评价托珠单抗联合甲氨蝶呤（MTX）与MTX单药治疗对MTX反应不足的中重度类风湿关节炎患者在预防结构性关节损伤、改善身体功能和疾病活动性方面的疗效和安全性。一项为期2年的随机、双盲、安慰剂对照试验共招募了1,196例患者。患者每4周一次接受托珠单抗（8 mg/kg或4 mg/kg）或安慰剂加MTX。从第16周开始提供补救治疗。第一年的结果已经公布。托珠单抗8 mg/kg + MTX组和托珠单抗4 mg/kg + MTX组总Genant改良Sharp评分的平均变化分别为0.29和0.34，而安慰剂+MTX组为1.13（两组比较P < 0.0001）。健康评估问卷残疾指数较基线变化曲线下面积的方差分析显示，托珠单抗8 mg/kg和4 mg/kg组（分别为-144.1和-128.4单位）的降幅大于安慰剂组（-58.1单位;两项比较P < 0.0001）。接受8 mg/kg托珠单抗治疗的患者中，美国流变学学会改善20%、50%和70%的患者比例以及28个关节疾病活动评分缓解的患者比例高于接受安慰剂治疗的患者（所有比较均P < 0.0001）。托珠单抗的安全性特征与既往研究中的特征一致。感染是最常见的不良事件和严重不良事件。这项研究的结果表明，托珠单抗联合MTX比单独MTX更能抑制关节损伤和改善身体功能。托珠单抗具有良好的安全性特征。
Objective. To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX.Methods. A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented.Results. Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events.Conclusion. The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile.