Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.
Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.
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DOI：
10.1136/annrheumdis-2015-207628
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发表时间：
2016-06
影响因子：
27.4
通讯作者：
Mitchell N
中科院分区：
文献类型：
--
作者：
Burmester GR;Rigby WF;van Vollenhoven RF;Kay J;Rubbert-Roth A;Kelman A;Dimonaco S;Mitchell N
托珠单抗（TCZ）是一种抗白细胞介素-6受体抗体，以前尚未在仅由早期类风湿性关节炎（RA）患者组成的人群中评估其疗效。在一项双盲随机对照试验（FUNCTION）中，将1162例未接受过甲氨蝶呤（MTX）的早期进展性RA患者随机（1：1：1：1）分配至4个治疗组之一：4 mg/kg TCZ +MTX、8 mg/kg TCZ+MTX、8 mg/kg TCZ+安慰剂和安慰剂+MTX（对照组）。 主要结果是在第24周根据疾病活动性评分使用28个关节（DAS 28-红细胞沉降率（ESR）<2.6）缓解。还评价了影像学和身体功能结局。第52周报告结果。意向治疗人群包括1157例患者。在第24周，接受8 mg/kg TCZ+MTX和8 mg/kg TCZ+安慰剂的患者比接受安慰剂+MTX的患者显著更多地实现了DAS 28-ESR缓解（45%和39% vs 15%; p<0.0001）。 第52周时，8 mg/kg TCZ+MTX组在放射学疾病进展和身体功能方面的改善也显著大于安慰剂+MTX组（货车der Heijde改良总Sharp评分较基线的平均变化为0.08 vs 1.14（p=0.0001）;健康评估残疾指数平均降低为-0.81 vs-0.64（p=0.0024））。此外，8 mg/kg TCZ+安慰剂组和4 mg/kg TCZ+MTX组在这些关键次要终点方面的临床疗效至少与MTX一样有效。 治疗组之间的严重不良事件相似。在8 mg/kg TCZ+MTX组中，20%的患者发生了导致提前停药的不良事件。 TCZ与MTX联合或作为单药治疗早期RA患者有效。ClinicalTrials.gov，编号NCT 01007435
The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28–erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52. The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde–modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, −0.81 vs −0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group. TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA. ClinicalTrials.gov, number NCT01007435