A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis
A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis
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DOI：
10.1136/gut.2005.081794
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发表时间：
2006-09-01
期刊：
影响因子：
24.5
通讯作者：
Hibi, T.
中科院分区：
文献类型：
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作者：
Ogata, H.;Matsui, T.;Hibi, T.
背景和目的：对于溃疡性结肠炎(UC)患者，静脉注射环孢素是一种替代全结肠切除术的治疗方案，而口服他克莫司的益处尚未明确，并基于几项非对照研究的报道。方法：难治性活动期UC患者随机分为高谷浓度(10~15 ng/ml)组(n=21)、低谷浓度(5~10 ng/ml)组(n=22)和安慰剂组(n=20)。患者每天两次接受0.05 mg/kg的他克莫司或安慰剂的初始口服剂量。根据疾病活动性指数(DAI)评分对60名患者进行疗效评估。58名患者接受了他克莫司的额外治疗，并在10周的开放标签扩展中进行了疗效评估。结果：HT组68.4%的患者DAI评分(4分，所有类别都有改善)与安慰剂组的10.0%(p<；0.001)相比有改善。HT组临床缓解率为20.0%，粘膜愈合率为78.9%。在开放标签扩展试验中，55.2%的患者在第10周时DAI评分有所改善。泼尼松龙的平均剂量从研究开始时的19.7mgd降至10wk时的7.8mgd。HT组的副作用发生率显著高于安慰剂组(p=0.043)。最常见的事件是轻度手指颤抖。结论：口服他克莫司对难治性UC的诱导缓解治疗具有剂量依赖性的有效性和安全性。就两周治疗的疗效而言，最佳靶向范围似乎是10-15 ng/ml。
Background and aims: Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies.Methods: Patients with refractory active UC were randomly assigned to a high trough concentration (10 15 ng/ml) group (HT group) (n = 21), low trough concentration (5 - 10 ng/ ml) group (LT group) (n = 22), or placebo group (n = 20). Patients received an initial oral dose of 0.05 mg/ kg tacrolimus or placebo twice daily. Efficacy was evaluated in 60 patients based on a disease activity index (DAI) score. Fifty eight patients had additional treatment with tacrolimus and were evaluated for efficacy in a 10 week open label extension.Results: An improvement in DAI score (> 4 points, all categories improved) was observed for 68.4% of cases in the HT group compared with 10.0% in the placebo group (p < 0.001). In the HT group, 20.0% of patients had clinical remission and 78.9% had mucosal healing. In the open label extension, 55.2% of all patients had an improved DAI score at week 10. Mean dose of prednisolone was reduced from 19.7 mg/ day at study entry to 7.8 mg/ day at week 10. The incidence of side effects in the HT group was significantly higher than that of the placebo group (p = 0.043). The most common event was mild finger tremor.Conclusions: Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC. The optimal target range appears to be 10 - 15 ng/ ml in terms of efficacy with two week therapy.