Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis
Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis
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DOI：
10.1056/nejmoa1905725
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发表时间：
2019-09-26
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：
Sands, Bruce E.;Peyrin-Biroulet, Laurent;Schreiber, Stefan
研究背景溃疡性结肠炎的治疗目前广泛采用生物疗法。这些治疗炎症性肠病患者的头对头试验是lacked.MethodsIn阶段3b，双盲，双模拟，在34个国家的245个中心进行随机试验，我们比较了Vedolizumab与阿达木单抗在成人中度至重度活动性溃疡性结肠炎，以确定是否Vedolizumab是上级。允许高达25%的患者既往暴露于阿达木单抗以外的肿瘤坏死因子抑制剂。患者被分配在第1天和第2、6、14、22、30、38和46周接受300 mg Vedolizumab输注（加安慰剂注射）或皮下注射40 mg阿达木单抗，第1周总剂量为160 mg，第2周为80 mg，此后每2周一次40 mg，直至第50周（加安慰剂输注）。两组均不允许剂量递增。主要结局为第52周时的临床缓解（定义为4个马约量表组分中任何一个的总分为1 [范围，0 - 3]）。为了控制I类错误，采用分层检验程序分析疗效结局，变量顺序如下：临床缓解，内镜改善（马约内镜组件的分项评分为0 - 1），结果共有769例患者接受随机分组，并接受至少一剂Vedolizumab治疗（383例患者）或阿达木单抗（386例患者）。第52周时，Vedolizumab组观察到临床缓解的患者百分比高于阿达木单抗组（31.3% vs. 22.5%;差异，8.8个百分点; 95%置信区间[CI]，2.5 - 15.0; P=0.006），内镜检查改善（39.7% vs. 27.7%;差异，11.9个百分点; 95% CI，5.3至18.5; P
BackgroundBiologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.MethodsIn a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of 1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.ResultsA total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P=0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P