溃疡性结肠炎是一种结、直肠粘膜的弥漫性炎症，其临床特点为原因不明的、时好时坏血性腹泻。在急性发作期应用糖皮质激素治疗的价值是肯定的，但有一部分急性溃疡性结肠炎患者对静脉滴注皮质类固醇激素无效，称为糖皮质激素抵抗性溃疡结肠炎。

糖皮质激素抵抗型溃疡性结肠炎是指任何部位的溃疡性结肠炎,曾采用过最大剂量的氨基水杨酸类药物口服和/或局部治疗无效, 尽管采用糖皮质激素治疗, 症状仍未缓解者。糖皮质激素依赖型指糖皮质激素治疗有效，但减量即复发的溃疡性结肠炎患者。

对于糖皮质激素抵抗型溃疡性结肠炎患者进行免疫抑制剂治疗，可以有效抑制病情进展，避免外科切除结肠，临床常用的免疫抑制剂包括环孢素和注射用英夫利昔单抗。对于这两种免疫抑制剂在治疗糖皮质激素抵抗型溃疡性结肠炎患者的区别目前还没有明确的研究，近期发表于《柳叶刀 胃肠道疾病》子刊的一项研究对这两种免疫抑制剂的有效性和安全性进行了评估。

这是一项平行、开方、随机控制实验，实验纳入了2007年6月1日到2010年8月31日，来自欧洲27个治疗中心的患者。患者的年龄均在18岁以上，已经确诊为急性溃疡性结肠炎，静脉滴注糖皮质激素治疗效果不佳，并且之前从未使用环孢素或注射用英夫利昔单抗治疗过。将115名患者随机分为两组，58名接受静脉滴注糖皮质激素和环孢素治疗，57名接受静脉滴注糖皮质激素和英夫利昔单抗治疗。将治疗第7天临床无应答、第7到98天之间出现病情复发、治疗出现严重不良反应而中断、不得已行外科手术及患者死亡都排除出实验组。

结果显示，环孢素治疗组有35名病人治疗失败，9个出现严重不良反应，英夫利昔单抗治疗组有31名患者治疗失败，14个出现严重不良反应。治疗效果上两组没有差异。基于此项实验分析的结果，专家认为，在治疗对静脉内皮质类固醇激素治疗应答不佳的溃疡性结肠炎患者中。环孢素并不比英夫利昔单抗更加有效，在临床治疗糖皮质激素抵抗型溃疡性结肠炎中，选择何种免疫抑制剂应根据实际临床情况结合医生经验进行。

Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial

Background

Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication.

Methods

In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and Clinical Trials. gov(NCT00542152).

Findings

115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI −7 to 19; p=0·52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events.

Interpretation

Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience.