Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis
Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis
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DOI：
10.1002/ibd.21853
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发表时间：
2012-05-01
影响因子：
4.9
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
--
作者：
Ogata, Haruhiko;Kato, Jun;Hibi, Toshifumi
背景：我们报告了一项口服他克莫司（FK 506）治疗激素难治性溃疡性结肠炎（UC）的多中心研究。研究方法：在一项安慰剂对照、双盲研究中，62例类固醇难治性中重度UC患者随机分为他克莫司组或安慰剂组，治疗2周。使用疾病活动指数（DAI）对患者进行评估。作为入选标准，患者的DAI总分必须≥ 6，粘膜外观分项评分为2或3。临床应答定义为所有DAI分项评分的改善。粘膜愈合定义为粘膜外观分项评分为0或1。临床缓解定义为总DAI评分=2，单个分项评分为0或1。结果：他克莫司组进入研究时的平均总DAI评分为9.8 ± 1.61，安慰剂组为9.1 ± 1.05。第2周时，他克莫司组的临床应答率为50.0%（16/32），安慰剂组为13.3%（4/30）（P = 0.003）。观察到的粘膜愈合率在他克莫司组为43.8%（14/32），在安慰剂组为13.3%（4/30）（P = 0.012），观察到的临床缓解率在他克莫司组为9.4%（3/32），在安慰剂组为0.0%（0/30）（P = 0.238）。本研究中的治疗耐受性良好，只有轻微的副作用。结论：口服他克莫司治疗激素难治性UC患者可缩短急性期并诱导粘膜快速愈合。这些结果表明，他克莫司治疗是有用的替代治疗激素难治性UC。（Inflamm Bowel Dis 2011;）
Background: We report a multicenter study of oral tacrolimus (FK506) therapy in steroid-refractory ulcerative colitis (UC). Methods: In a placebo-controlled, double-blind study, 62 patients with steroid-refractory, moderate-to-severe UC were randomized into either a tacrolimus group or a placebo for 2 weeks. Patients were evaluated using the Disease Activity Index (DAI). As an entry criterion, patients had to have a total DAI score of 6 or more as well as a mucosal appearance subscore of 2 or 3. Clinical response was defined as improvement in all DAI subscores. Mucosal healing was defined as mucosal appearance subscore of 0 or 1. Clinical remission was defined as a total DAI score =2 with an individual subscore of 0 or 1. Results: The mean total DAI score at study entry was 9.8 +/- 1.61 in the tacrolimus group and 9.1 +/- 1.05 in the placebo group. At week 2 the clinical response rate was 50.0% (16/32) in the tacrolimus group and 13.3% (4/30) in the placebo group (P = 0.003). The rate of mucosal healing observed was 43.8% (14/32) in the tacrolimus group and 13.3% (4/30) in the placebo group (P = 0.012) and the rate of clinical remission observed was 9.4% (3/32) in the tacrolimus group and 0.0% (0/30) in the placebo group (P = 0.238). The therapies in this study were well tolerated, with only minor side effects. Conclusions: Oral tacrolimus therapy in patients with steroid-refractory UC shortened the acute phase and induced rapid mucosal healing. These results suggest that tacrolimus therapy is useful as an alternative therapy for steroid-refractory UC. (Inflamm Bowel Dis 2011;)