Treatment of Active Crohn's Disease With MLN0002, a Humanized Antibody to the α4β7 Integrin
Treatment of Active Crohn's Disease With MLN0002, a Humanized Antibody to the α4β7 Integrin
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DOI：
10.1016/j.cgh.2008.06.007
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发表时间：
2008-12-01
影响因子：
12.6
通讯作者：
Parikh, Asit
中科院分区：
文献类型：
--
作者：
Feagan, Brian G.;Greenberg, Gordon R.;Parikh, Asit
背景和目标：选择性阻断胃肠道中淋巴细胞-血管内皮相互作用是炎症性肠病的一种有前景的治疗策略。这项随机、双盲、对照试验评估了MLN 0002（一种靶向α 4 β 7整联蛋白的单克隆抗体）在活动性克罗恩病患者中的疗效和安全性。研究方法：患者在第1天和第29天通过静脉输注随机接受MLN 0002 2.0 mg/kg（n = 65）、MLN 0002 0.5 mg/kg（n = 62）或安慰剂（n = 58）。主要疗效终点是第57天的临床反应（克罗恩病活动指数[CDAI]评分下降>= 70分）。次要终点是临床缓解患者的比例（CDAI评分= CDAI下降100分）。测量人抗人抗体水平。结果：MLN 0002 2.0 mg/kg、MLN 0002 0.5 mg/kg和安慰剂组第57天的临床应答率分别为53%、49%和41%。第57天的临床缓解率分别为37%、30%和21%（2.0 mg/kg与安慰剂比较，P = 0.04）。在第57天，2.0和0.5-mg/kg组中12%和34%的患者具有临床显著的人抗人抗体水平（滴度> 1：125）。有1例输注相关超敏反应。最常见的严重不良事件是克罗恩病恶化。结论：这项II期研究表明MLN 0002治疗对临床缓解具有剂量依赖性获益作用。活动性克罗恩病患者对MLN 0002耐受良好。
Background & Aims: Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease. This randomized, double-blind, controlled trial assessed the efficacy and safety of MLN0002, a monoclonal antibody targeting the alpha 4 beta 7 integrin, in patients with active Crohn's disease. Methods: Patients were randomized to receive MLN0002 2.0 mg/kg (n = 65), MLN0002 0.5 mg/kg (n = 62), or placebo (n = 58) by intravenous infusion on days 1 and 29. The primary efficacy end point was clinical response (>= 70-point decrement in the Crohn's Disease Activity Index [CDAI] score) on day 57. Secondary end points were the proportions of patients with clinical remission (CDAI score = 100-point decrement in CDAI). Human antihuman antibody levels were measured. Results: Clinical response rates at day 57 were 53%, 49%, and 41% in the MLN0002 2.0 mg/kg, MLN0002 0.5 mg/kg, and placebo groups. Clinical remission rates at day 57 were 37%, 30%, and 21%, respectively (P = .04 for the 2.0 mg/kg vs placebo comparison). At day 57, 12% and 34% of patients in the 2.0 and 0.5-mg/kg groups had clinically significant human anti-human antibody levels (titers > 1:125). There was one infusion-related hypersensitivity reaction. The most common serious adverse event was worsening of Crohn's disease. Conclusions: This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission. MLN0002 was well tolerated in patients with active Crohn's disease.