Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease
Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease
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DOI：
10.1056/nejmoa1602773
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发表时间：
2016-11-17
影响因子：
158.5
通讯作者：
Rutgeerts, P.
中科院分区：
文献类型：
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作者：
Feagan, B. G.;Sandborn, W. J.;Rutgeerts, P.
研究人员评估了白介素-12和白介素-23的p40亚基的单克隆抗体，作为两个中度至重度活动性克罗恩病人群的静脉诱导治疗。乌司奴单抗也被评估为皮下维持therapy.METHODSWe随机分配患者接受单次静脉注射剂量的乌司奴单抗（无论是130毫克或约6毫克每公斤体重）或安慰剂在两个诱导试验。UNITI-1试验纳入了741例符合肿瘤坏死因子（TNF）拮抗剂原发性或继发性无应答或有不可接受的副作用标准的患者。UNITI-2试验包括628例常规治疗失败或发生不可接受的副作用的患者。完成这些诱导试验的患者随后参加IM-UNITI，其中397例对乌司奴单抗有反应的患者被随机分配接受90 mg乌司奴单抗皮下维持注射（每8周一次或每12周一次）或安慰剂。诱导试验的主要终点是第6周的临床应答（定义为克罗恩病活动指数[CDAI]评分较基线降低≥ 100分或CDAI评分
BACKGROUNDUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.METHODSWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of = 100 points or a CDAI score