Certolizumab pegol for the treatment of Crohn's disease
Certolizumab pegol for the treatment of Crohn's disease
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DOI：
10.1056/nejmoa067594
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发表时间：
2007-07-19
影响因子：
158.5
通讯作者：
Schreiber, Stefan
中科院分区：
文献类型：
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作者：
Sandborn, William J.;Feagan, Brian G.;Schreiber, Stefan
背景：Certolizumab pegol是一种聚乙二醇化人源化Fab‘片段，与肿瘤坏死因子(α)结合。方法：在一项随机、双盲、安慰剂对照试验中，我们评估了certolizumab pegol对662例成人中重度克罗恩病的疗效。患者根据C反应蛋白(CRP)的基线水平进行分层，并被随机分配到0、2和4周皮下注射400 mg certolizumab pegol或安慰剂，然后每4周接受一次。结果：在基线CRP水平至少为每升10 mg的患者中，certolizumab组有37%的患者在第6周有反应，而安慰剂组有26%的患者有反应(P=0.04)。在第6周和第26周，相应的数值分别为22%和12%(P=0.05)。在总体人群中，Certolizumab组和安慰剂组在第6周的有效率分别为35%和27%(P=0.02)，在第6周和第26周的有效率分别为23%和16%(P=0.02)。治疗6周和26周，两组缓解率差异无统计学意义(P=0.17)。Certolizumab组和安慰剂组分别有10%和7%的患者报告了严重不良事件；分别有2%和不到1%的患者报告了严重感染。在Certolizumab组，8%的患者出现了药物抗体，2%的患者出现了抗核抗体。结论：在中重度克罗恩病患者中，与安慰剂相比，Certolizumab pegol诱导和维持治疗的应答率略有改善，但缓解率没有显著改善。
Background: Certolizumab pegol is a pegylated humanized Fab' fragment that binds tumor necrosis factor (alpha).Methods: In a randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol in 662 adults with moderate-to-severe Crohn's disease. Patients were stratified according to baseline levels of C-reactive protein (CRP) and were randomly assigned to receive either 400 mg of certolizumab pegol or placebo subcutaneously at weeks 0, 2, and 4 and then every 4 weeks. Primary end points were the induction of a response at week 6 and a response at both weeks 6 and 26.Results: Among patients with a baseline CRP level of at least 10 mg per liter, 37% of patients in the certolizumab group had a response at week 6, as compared with 26% in the placebo group (P=0.04). At both weeks 6 and 26, the corresponding values were 22% and 12%, respectively (P=0.05). In the overall population, response rates at week 6 were 35% in the certolizumab group and 27% in the placebo group (P=0.02); at both weeks 6 and 26, the response rates were 23% and 16%, respectively (P=0.02). At weeks 6 and 26, the rates of remission in the two groups did not differ significantly (P=0.17). Serious adverse events were reported in 10% of patients in the certolizumab group and 7% of those in the placebo group; serious infections were reported in 2% and less than 1%, respectively. In the certolizumab group, antibodies to the drug developed in 8% of patients, and antinuclear antibodies developed in 2%.Conclusions: In patients with moderate-to-severe Crohn's disease, induction and maintenance therapy with certolizumab pegol was associated with a modest improvement in response rates, as compared with placebo, but with no significant improvement in remission rates.