Hanauer Stephen B, Feagan Brian G, Lichtenstein Gary R, Mayer Lloyd F, Schreiber S, Colombel Jean Frederic, Rachmilewitz Daniel, Wolf Douglas C, Olson Allan, Bao Weihang, Rutgeerts Paul
Department of Gastroenterology and Nutrition, University of Chicago Medical Center, Chicago, IL 60637, USA.
Lancet. 2002 May 4;359(9317):1541-9. doi: 10.1016/S0140-6736(02)08512-4.
We did a randomised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn's disease who respond to a single infusion of infliximab.
573 patients with a score of at least 220 on the Crohn's disease activity index (CDAI) received a 5 mg/kg intravenous infusion of infliximab at week 0. After assessment of response at week 2, patients were randomly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 (group I), repeat infusions of 5 mg/kg infliximab at the same timepoints (group II), or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg (group III). The prespecified co-primary endpoints were the proportion of patients who responded at week 2 and were in remission (CDAI <150) at week 30 and the time to loss of response up to week 54 in patients who responded. Analyses of the co-primary endpoints were by intention to treat.
335 (58%) patients responded to a single infusion of infliximab within 2 weeks. At week 30, 23 of 110 (21%) group I patients were in remission, compared with 44 of 113 (39%) group II (p=0.003) and 50 of 112 (45%) group III (p=0.0002) patients. Thus, patients in groups II and III combined were more likely to sustain clinical remission than patients in group I (odds ratio 2.7, 95% CI 1.6-4.6). Throughout the 54-week trial, the median time to loss of response was 38 weeks (IQR 15 to >54) and more than 54 weeks (21 to >54) for groups II and III, respectively, compared with 19 weeks (10-45) for group I (p=0.002 and p=0.0002, respectively). Infliximab safety was consistent with that seen in other trials of infliximab in Crohn's disease and rheumatoid arthritis. In particular, the incidence of serious infections was similar across treatment groups.
Patients with Crohn's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54, to discontinue corticosteroids, and to maintain their response for a longer period of time, if infliximab treatment is maintained every 8 weeks.
我们进行了一项随机对照试验，以评估英夫利昔单抗维持治疗对单剂量英夫利昔单抗治疗有效的活动性克罗恩病患者的益处。
573名克罗恩病活动指数（CDAI）评分至少为220的患者在第0周接受了5mg/kg英夫利昔单抗静脉输注。在第2周评估反应后，患者被随机分配在第2周和第6周接受安慰剂重复输注，此后每8周一次，直至第46周（I组）；在相同时间点接受5mg/kg英夫利昔单抗重复输注（II组）；或在第2周和第6周接受5mg/kg英夫利昔单抗，随后接受10mg/kg（III组）。预先设定的共同主要终点是在第2周有反应且在第30周处于缓解期（CDAI<150）的患者比例，以及有反应的患者至第54周失去反应的时间。共同主要终点的分析采用意向性分析。
335名（58%）患者在2周内对单剂量英夫利昔单抗有反应。在第30周，I组110名患者中有23名（21%）处于缓解期，相比之下，II组113名患者中有44名（39%）（p=0.003），III组112名患者中有50名（45%）（p=0.0002）。因此，II组和III组合并的患者比I组患者更有可能维持临床缓解（优势比2.7，95%CI 1.6-4.6）。在整个54周的试验中，II组和III组失去反应的中位时间分别为38周（IQR 15至>54）和超过54周（21至>54），而I组为19周（10-45）（分别为p=0.002和p=0.0002）。英夫利昔单抗的安全性与其他英夫利昔单抗治疗克罗恩病和类风湿关节炎的试验中观察到的一致。特别是，各治疗组严重感染的发生率相似。
对初始剂量英夫利昔单抗有反应的克罗恩病患者，如果每8周维持英夫利昔单抗治疗，在第30周和第54周更有可能处于缓解期、停用皮质类固醇，并在更长时间内维持反应。
