Rutgeerts Paul, Sandborn William J, Feagan Brian G, Reinisch Walter, Olson Allan, Johanns Jewel, Travers Suzanne, Rachmilewitz Daniel, Hanauer Stephen B, Lichtenstein Gary R, de Villiers Willem J S, Present Daniel, Sands Bruce E, Colombel Jean Frédéric
University Hospital Gasthuisberg, Leuven, Belgium.
N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis.
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.
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< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons).
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. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)
英夫利昔单抗是一种针对肿瘤坏死因子α的嵌合单克隆抗体，是治疗克罗恩病的常用药物，但不适用于溃疡性结肠炎。
两项随机、双盲、安慰剂对照研究——分别为溃疡性结肠炎活性试验1和2（ACT 1和ACT 2）——评估了英夫利昔单抗在成年溃疡性结肠炎患者诱导和维持治疗中的疗效。在每项研究中，364例尽管接受了联合药物治疗但仍患有中度至重度活动性溃疡性结肠炎的患者在第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毫克或10毫克），然后每8周注射一次，直至第46周（ACT 1）或第22周（ACT 2）。ACT 1中患者随访54周，ACT 2中患者随访30周。
在ACT 1中，接受5毫克英夫利昔单抗治疗的患者中有69%在第8周有临床反应，接受10毫克英夫利昔单抗治疗的患者中有61%有临床反应，而接受安慰剂治疗的患者中这一比例为37%（与安慰剂组相比，两项比较P均<0.001）。临床反应定义为梅奥评分至少降低3分且降低至少30%，同时直肠出血分项评分至少降低1分或直肠出血绝对分项评分为0或1。在ACT 2中，接受5毫克英夫利昔单抗治疗的患者中有64%在第8周有临床反应，接受10毫克英夫利昔单抗治疗的患者中有69%有临床反应，而接受安慰剂治疗的患者中这一比例为29%（与安慰剂组相比，两项比较P均<0.001）。在两项研究中，接受英夫利昔单抗治疗的患者在第30周更有可能出现临床反应（所有比较P≤0.002）。在ACT 1中，接受5毫克或10毫克英夫利昔单抗治疗的患者在第54周有临床反应的比例更高（分别为45%和44%），高于接受安慰剂治疗的患者（20%，与安慰剂组的两项比较P均<0.001）。
在第0、2和6周以及此后每8周接受英夫利昔单抗治疗的中度至重度活动性溃疡性结肠炎患者，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。（ClinicalTrials.gov编号，NCT00036439和NCT00096655。）
