潰瘍性結(jié)腸炎是一種結(jié)、直腸粘膜的彌漫性炎癥，其臨床特點為原因不明的、時好時壞血性腹瀉。在急性發(fā)作期應(yīng)用糖皮質(zhì)激素治療的價值是肯定的，但有一部分急性潰瘍性結(jié)腸炎患者對靜脈滴注皮質(zhì)類固醇激素無效，稱為糖皮質(zhì)激素抵抗性潰瘍結(jié)腸炎。

    糖皮質(zhì)激素抵抗型潰瘍性結(jié)腸炎是指任何部位的潰瘍性結(jié)腸炎,曾采用過最大劑量的氨基水楊酸類藥物口服和/或局部治療無效, 盡管采用糖皮質(zhì)激素治療, 癥狀仍未緩解者。糖皮質(zhì)激素依賴型指糖皮質(zhì)激素治療有效，但減量即復(fù)發(fā)的潰瘍性結(jié)腸炎患者。

    對于糖皮質(zhì)激素抵抗型潰瘍性結(jié)腸炎患者進行免疫抑制劑治療，可以有效抑制病情進展，避免外科切除結(jié)腸，臨床常用的免疫抑制劑包括環(huán)孢素和注射用英夫利昔單抗。對于這兩種免疫抑制劑在治療糖皮質(zhì)激素抵抗型潰瘍性結(jié)腸炎患者的區(qū)別目前還沒有明確的研究，近期發(fā)表于《柳葉刀 胃腸道疾病》子刊的一項研究對這兩種免疫抑制劑的有效性和安全性進行了評估。

    這是一項平行、開方、隨機控制實驗，實驗納入了2007年6月1日到2010年8月31日，來自歐洲27個治療中心的患者?；颊叩哪挲g均在18歲以上，已經(jīng)確診為急性潰瘍性結(jié)腸炎，靜脈滴注糖皮質(zhì)激素治療效果不佳，并且之前從未使用環(huán)孢素或注射用英夫利昔單抗治療過。將115名患者隨機分為兩組，58名接受靜脈滴注糖皮質(zhì)激素和環(huán)孢素治療，57名接受靜脈滴注糖皮質(zhì)激素和英夫利昔單抗治療。將治療第7天臨床無應(yīng)答、第7到98天之間出現(xiàn)病情復(fù)發(fā)、治療出現(xiàn)嚴重不良反應(yīng)而中斷、不得已行外科手術(shù)及患者死亡都排除出實驗組。

    結(jié)果顯示，環(huán)孢素治療組有35名病人治療失敗，9個出現(xiàn)嚴重不良反應(yīng)，英夫利昔單抗治療組有31名患者治療失敗，14個出現(xiàn)嚴重不良反應(yīng)。治療效果上兩組沒有差異?；诖隧棇嶒灧治龅慕Y(jié)果，專家認為，在治療對靜脈內(nèi)皮質(zhì)類固醇激素治療應(yīng)答不佳的潰瘍性結(jié)腸炎患者中。環(huán)孢素并不比英夫利昔單抗更加有效，在臨床治療糖皮質(zhì)激素抵抗型潰瘍性結(jié)腸炎中，選擇何種免疫抑制劑應(yīng)根據(jù)實際臨床情況結(jié)合醫(yī)生經(jīng)驗進行。

    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.