Infliximab for induction and maintenance therapy for ulcerative colitis
Infliximab for induction and maintenance therapy for ulcerative colitis
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DOI：
10.1056/nejmx060025
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
U. Gasthuisberg
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文献类型：
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作者：
U. Gasthuisberg
背景：英夫利昔单抗是一种靶向肿瘤坏死因子α的嵌合单克隆抗体，是治疗克罗恩病但不治疗溃疡性结肠炎的有效方法。方法：两项随机、双盲、安慰剂对照研究——活动性溃疡性结肠炎试验1和试验2（分别为ACT 1和ACT 2）——评估英夫利昔单抗诱导和维持治疗成人溃疡性结肠炎的疗效。在每项研究中，364例中至重度活动性溃疡性结肠炎患者尽管同时接受了药物治疗，但在第0、2和6周静脉注射安慰剂或英夫利昔单抗（每公斤体重5 mg或10 mg），然后每8周静脉注射一次，直到第46周（ACT 1）或第22周（ACT 2）。ACT 1组随访54周，ACT 2组随访30周。结果：在ACT 1中，69%的接受5mg英夫利昔单抗治疗的患者和61%的接受10mg英夫利昔单抗治疗的患者在第8周有临床反应，而接受安慰剂治疗的患者中有37%的患者有临床反应（与安慰剂相比，两组比较P均为0.001）。缓解被定义为梅奥评分降低至少3分和至少30%，同时直肠出血亚评分降低至少1分或绝对直肠出血亚评分为0或1。在ACT 2中，接受5mg英夫利昔单抗治疗的患者中有64%和接受10mg英夫利昔单抗治疗的患者中有69%在第8周有临床反应，而接受安慰剂治疗的患者中有29%有临床反应（与安慰剂相比，两组比较P均为0.001）。在这两项研究中，接受英夫利昔单抗治疗的患者更有可能在第30周出现临床反应（所有比较的P≤0.002）。在ACT 1中，接受5mg或10mg inflix imab的患者在第54周的临床反应（分别为45%和44%）多于接受安慰剂的患者（20%，两种比较的P0.001）。结论：中重度活动性溃疡性结肠炎患者在第0、2和6周以及之后每8周接受英夫利昔单抗治疗时，在第8、30和54周比接受安慰剂治疗的患者更有可能出现临床反应。
BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P 0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P 0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P ≤0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of inflix imab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P0.001 for both comparisons) . CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.