Infliximab for the treatment of fistulas in patients with Crohn's disease
Infliximab for the treatment of fistulas in patients with Crohn's disease
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DOI：
10.1056/nejm199905063401804
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发表时间：
1999-05-06
影响因子：
158.5
通讯作者：
van Deventer, SJH
中科院分区：
文献类型：
--
作者：
Present, DH;Rutgeerts, P;van Deventer, SJH
背景肠外瘘是克罗恩病的严重并发症，且难以治疗。英夫利昔单抗是一种针对肿瘤坏死因子 a 的嵌合单克隆抗体，最近被开发用于治疗克罗恩病。我们进行了一项英夫利昔单抗治疗克罗恩病患者瘘管的随机、多中心、双盲、安慰剂对照试验。 方法 该研究纳入了 94 名患有克罗恩病并发症的腹部或肛周引流瘘至少三个月的成年患者。患者被随机分配接受三种治疗之一：安慰剂（31 名患者）、每公斤体重 5 毫克英夫利昔单抗（31 名患者）或每公斤体重 10 毫克英夫利昔单抗（32 名患者）；所有三种药物均在第 0、2 和 6 周进行静脉注射。主要终点是在两次或多次连续研究访问中观察到的引流瘘管数量较基线减少 50% 或更多。次要终点是所有瘘管闭合。 结果 接受 5 mg/kg 英夫利昔单抗治疗的患者中有 68% 的患者和接受 10 mg/kg 英夫利昔单抗治疗的患者中有 56% 达到了主要终点，而安慰剂组中这一比例为 26%（分别为 P=0.002 和 P=0.02）。此外，在接受 5 mg/kg 英夫利昔单抗治疗的患者中，有 55% 的患者和在接受 10 mg/kg 英夫利昔单抗治疗的患者中，有 38% 的患者所有瘘管均已闭合，而在接受安慰剂治疗的患者中，这一比例为 13%（分别为 P=0.001 和 P=0.04）。瘘管保持闭合状态的中位时间为三个月。所有组中超过 60% 的患者都出现了不良事件。对于接受英夫利昔单抗治疗的患者，最常见的是头痛、脓肿、上呼吸道感染和疲劳。结论英夫利昔单抗是治疗克罗恩病患者瘘管的有效方法。 （N Engl J Med 1999；340：1398-405。）(C) 1999，马萨诸塞州医学会。
Background Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor a, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease.Methods The study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas.Results Sixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in ail the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue.Conclusions Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease. (N Engl J Med 1999;340:1398-405.) (C) 1999, Massachusetts Medical Society.