Adrenomedullin Therapy in Patients with Refractory Ulcerative Colitis: A Case Series
Adrenomedullin Therapy in Patients with Refractory Ulcerative Colitis: A Case Series
复制标题
DOI：
10.1007/s10620-015-3917-0
复制
发表时间：
2016-03-01
影响因子：
3.1
通讯作者：
Kitamura, Kazuo
中科院分区：
文献类型：
--
作者：
Ashizuka, Shinya;Inatsu, Haruhiko;Kitamura, Kazuo
肾上腺髓质素（AM）是一种多功能的生物活性肽，在几种实验模型中对炎症性肠病具有改善作用。我们报道了第一例AM输注显著改善难治性溃疡性结肠炎（UC）患者的症状和结肠镜检查结果的病例。为了证实AM静脉滴注的有效性和安全性的可重复性，本初步研究评估了AM静脉给药在难治性UC患者中的临床可行性。7例活动性难治性UC患者参与并接受了AM静脉滴注（1.5 pmol/kg/min），每天8 h，持续14天，疾病活动指数（DAI）用药前、用药后2周、12周分别进行DAI评分，用药后DAI均明显改善。在2周内，在6名患者（85.7%）中观察到DAI显著下降（千分之一日元3点和千分之一日元30%），而在1名患者（14.3%）中观察到更适度的下降。总体平均DAI从基线时的9.3 +/- A 0.6改善至2周时的4.6 +/- A 0.8，然后改善至12周时的1.2 +/- A 0.5。内镜检查显示溃疡显著改善，粘膜愈合和瘢痕形成。4例患者在AM治疗后12个月保持临床缓解。AM给药使血浆AM浓度显著增加（约2.5倍），对血压和心率有轻微影响，但没有严重的不良反应。AM是一种潜在有用的药物，通过一种新的机制安全地诱导难治性UC患者的粘膜愈合和临床缓解。
Adrenomedullin (AM) is a multifunctional biologically active peptide that has an ameliorative effect against inflammatory bowel disease in several experimental models. We reported the first case where AM infusion dramatically improved symptoms and colonoscopy findings in patients with refractory ulcerative colitis (UC). To confirm the reproducibility of the efficacy and safety of AM infusion, this pilot study evaluated the clinical feasibility of intravenous administration of AM in patients with refractory UC.Seven patients with active refractory UC participated and received intravenous infusion of AM (1.5 pmol/kg/min) for 8 h daily for 14 days, and their Disease Activity Index (DAI) were evaluated before and 2 and 12 weeks after beginning AM administration.DAI were improved in all patients after AM administration. Within 2 weeks, marked declines in DAI (a parts per thousand yen3 points and a parts per thousand yen30 %) were observed in six patients (85.7 %), while a more modest decline was observed in one patient (14.3 %). Overall mean DAI improved from 9.3 +/- A 0.6 at baseline to 4.6 +/- A 0.8 at 2 weeks, and then to 1.2 +/- A 0.5 at 12 weeks. Endoscopic examination revealed substantial amelioration of ulcers, with mucosal healing and scarring. Four patients remained in clinical remission 12 months after AM treatment. AM administration produced significant increases in plasma AM concentrations (approximately 2.5-fold) that had a mild effect on blood pressure and heart rate, but with no serious adverse effects.AM is a potentially useful agent that acts via a novel mechanism to safely induce mucosal healing and clinical remission in patients with refractory UC.