Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial
Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial
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DOI：
10.1053/j.gastro.2005.11.030
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发表时间：
2006-02-01
期刊：
影响因子：
29.4
通讯作者：
Pollack, P
中科院分区：
文献类型：
--
作者：
Hanauer, SB;Sandborn, WJ;Pollack, P
背景与目的：肿瘤坏死因子阻断剂已被证明是克罗恩病（CD）的有效治疗策略。阿达木单抗是一种靶向肿瘤坏死因子（TNF）的人免疫球蛋白G1（IgG（1））单克隆抗体。进行了一项随机、双盲、安慰剂对照、剂量范围探索试验，以评价阿达木单抗诱导治疗在CD患者中的疗效。研究方法：共有299例中重度CD患者（未经抗TNF治疗）在第0周和第2周随机接受阿达木单抗40 mg/20 mg、80 mg/40 mg或：160 mg/80 mg或安慰剂皮下注射。主要终点是证明80 mg/40 mg、160 mg/80 mg和安慰剂组之间第4周缓解率（定义为克罗恩病活动指数评分< 150分）的显著差异。结果如下：阿达木单抗40 mg/20 mg、80 mg、140环和160 mg/80 mg组第4周的缓解率分别为18%（P =.36）、24%（P =.06）和36%（P =.001），安慰剂组为12%。除注射部位反应外，所有4个治疗组中不良事件的发生频率相似，注射部位反应在阿达木单抗治疗患者中更常见。结论：阿达木单抗在诱导初治抗TNF治疗的中重度克罗恩病患者缓解方面优于安慰剂，且效果上级。本研究中阿达木单抗的最佳诱导给药方案为：第0周160 mg，随后第2周80 mg。阿达木单抗耐受性良好。
Background & Aims: Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn's disease (CD). Adalimumab is a human immunoglobulin G1 (IgG(1)) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD. Methods: A total of 299 patients with moderate to severe CD naive to anti-TNF therapy were randomized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg, 80 mg/40 mg, or :160 mg,/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 (defined as a Crohn's Disease Activity Index score < 150 points) among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups. Results: The rates of remission at week 4 in the adalimumab 40 mg/20 mg, 80 mg,140 ring, and 160 mg/80 mg groups were 18% (P =.36), 24% (P =.06), and 36% (P =.001), respectively, and 12% in the placebo group. Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients. Conclusions: Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy. The optimal induction dosing regimen for adalimumab in this study was :160 mg at week 0 followed by 80 mg at week 2. Adalimumab was well tolerated.