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维多珠单抗与阿达木单抗治疗中度至重度溃疡性结肠炎的比较
Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis


Bruce E. Sands ... 其他 • 2019.09.26
相关阅读
• 对治疗溃疡性结肠炎的生物制剂开展的首项直接比较试验 • 轻至中度溃疡性结肠炎的治疗 • 溃疡性结肠炎的治疗

摘要


背景

生物疗法被广泛应用于溃疡性结肠炎患者。但目前尚无在炎性肠病患者中使用这些疗法的头对头直接比较试验。

 

方法

在34个国家245个研究中心开展的一项3b期、双盲、双模拟、随机、活性药对照试验中,我们在中度至重度活动期溃疡性结肠炎成人患者中比较了维多珠单抗(vedolizumab)和阿达木单抗,目的是确定维多珠单抗是否优于阿达木单抗。本试验允许最多25%的患者使用过阿达木单抗之外的肿瘤坏死因子抑制剂。患者被分配接受300 mg维多珠单抗静脉输入(在第1日以及第2、6、14、22、30、38和46周)+安慰剂注射或者40 mg阿达木单抗皮下注射(总剂量为第1周160 mg,第2周80 mg,之后每2周40 mg,直至第50周)+安慰剂输入。两组均不允许增加剂量。主要结局是第52周时的临床缓解(定义为梅奥量表[Mayo scale]总分≤2分[量表范围,0~12分,评分较高表示疾病较严重],并且在梅奥量表的4个组成部分中,没有任何分项评分>1分[范围,0~3分])。为了控制Ⅰ型错误,我们利用分级检验程序分析了疗效结局,变量顺序如下:第52周时的临床缓解、内镜结果改善(梅奥量表内镜结果部分的分项评分为0~1分)和不应用皮质类固醇情况下的缓解。

 

结果

共有769例患者被随机分组,并接受了至少1剂维多珠单抗(383例患者)或阿达木单抗(386例患者)治疗。第52周时,维多珠单抗组达到临床缓解(31.3% vs. 22.5%;差异,8.8个百分点;95%CI,2.5~15.0;P=0.006)和内镜结果改善(39.7% vs. 27.7%;差异,11.9个百分点;95%CI,5.3~18.5;P<0.001)的患者比例均高于阿达木单抗组。维多珠单抗组12.6%的患者和阿达木单抗组21.8%的患者达到了不应用皮质类固醇情况下的临床缓解(差异,-9.3个百分点;95% CI,-18.9~0.4)。在维多珠单抗组和阿达木单抗组中,根据暴露情况校正的感染发生率分别为23.4例/100患者-年和34.6例/100患者-年,严重感染发生率分别为1.6例100患者-年和2.2例/100患者-年。

 

结论

在这项对中度至重度活动期溃疡性结肠炎进行的试验中,在临床缓解和内镜结果改善方面,维多珠单抗优于阿达木单抗,但在不应用皮质类固醇情况下达到临床缓解方面,维多珠单抗并未优于阿达木单抗(由武田制药资助;VARSITY在ClinicalTrials.gov注册号为NCT02497469;在EudraCT注册号为2015-000939-33)。





作者信息

Bruce E. Sands, M.D., Laurent Peyrin-Biroulet, M.D., Ph.D., Edward V. Loftus, Jr., M.D., Silvio Danese, M.D., Jean-Frédéric Colombel, M.D., Murat Törüner, M.D., Laimas Jonaitis, M.D., Ph.D., Brihad Abhyankar, F.R.C.S., Jingjing Chen, Ph.D., Raquel Rogers, M.D., Richard A. Lirio, M.D., Jeffrey D. Bornstein, M.D., and Stefan Schreiber, M.D., Ph.D. for the VARSITY Study Group*
From the Icahn School of Medicine at Mount Sinai, New York (B.E.S., J.-F.C.); Nancy University Hospital, Nancy, France (L.P.-B.); Mayo Clinic College of Medicine, Rochester, MN (E.V.L.); Humanitas University, Milan (S.D.); Ankara University School of Medicine, Ankara, Turkey (M.T.); Lithuanian University of Health Sciences, Kaunas, Lithuania (L.J.); Takeda Development Centre Europe, London (B.A.); Takeda Development Center Americas, Cambridge, MA (J.C., R.R., R.A.L., J.D.B.); and the University Hospital Schleswig-Holstein, Kiel, Germany (S.S.). Address reprint requests to Dr. Sands at the Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl., Box 1069, New York, NY 10029, or at bruce.sands@mssm.edu; or to Dr. Schreiber at the Department of Medicine I, University Hospital Schleswig-Holstein, Rosalind-Franklin-Str. 12, Haus 5, 24105 Kiel, Germany, or at s.schreiber@mucosa.de. *A list of investigators in the VARSITY Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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