Miele Erasmo, Pascarella Filomena, Giannetti Eleonora, Quaglietta Lucia, Baldassano Robert N, Staiano Annamaria
Department of Pediatrics, University of Naples "Federico II", Naples, Italy.
Am J Gastroenterol. 2009 Feb;104(2):437-43. doi: 10.1038/ajg.2008.118. Epub 2009 Jan 20.
Several probiotic compounds have shown promise in the therapy of ulcerative colitis (UC). However, a strong sustained benefit remains to be seen. Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains remission in mild to moderate UC and reduces active inflammation in adult patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study were to assess the efficacy of VSL#3 on induction and maintenance of remission and to evaluate the safety and tolerability of the probiotic preparation therapy in children with active UC.
A total of 29 consecutive patients (mean age: 9.8 years; range: 1.7-16.1 years; female/male: 13/16) with newly diagnosed UC were randomized to receive either VSL#3 (weight-based dose, range: 450-1,800 billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with concomitant steroid induction and mesalamine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 2 months, 6 months, and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity index and a physician's global assessment were used to measure disease activity. At baseline, within 6 months and 12 months or at the time of relapse, all patients were assessed endoscopically and histologically.
All 29 patients responded to the inflammatory bowel disease (IBD) induction therapy. Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001). Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15 (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of follow-up (P=0.014; RR=0.32; CI=0.025-0.773; NNT=2). All 3 patients treated with VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and histological scores were significantly lower in the VSL#3 group than in the placebo group (P<0.05). There were no biochemical or clinical adverse events related to VSL#3.
This is the first pediatric, randomized, placebo-controlled trial that suggests the efficacy and safety of a highly concentrated mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its role in maintenance of remission.
几种益生菌化合物在溃疡性结肠炎（UC）治疗中已显示出前景。然而，持续的显著益处仍有待观察。非对照的初步研究表明，一种益生菌制剂（VSL#3）可维持轻至中度UC患者的缓解状态，并减轻成年患者的活动性炎症。我们这项为期1年的前瞻性、安慰剂对照、双盲研究的目的是评估VSL#3诱导和维持缓解的疗效，并评估该益生菌制剂疗法对活动性UC患儿的安全性和耐受性。
共有29例新诊断的UC患儿（平均年龄：9.8岁；范围：1.7 - 16.1岁；女/男：13/16）被随机分组，分别接受VSL#3（基于体重给药，范围：450 - 18000亿个细菌/天；n = 14）或相同的安慰剂（n = 15），同时接受类固醇诱导治疗和美沙拉嗪维持治疗。在诊断后1个月、2个月、6个月和1年或复发时这四个时间点对患儿进行前瞻性评估。使用Lichtiger结肠炎活动指数和医生的整体评估来衡量疾病活动度。在基线、6个月和12个月时或复发时，对所有患者进行内镜和组织学评估。
所有29例患者对炎症性肠病（IBD）诱导治疗均有反应。接受VSL#3和IBD治疗的13例患者（92.8%）实现缓解，接受安慰剂和IBD治疗的4例患者（36.4%）实现缓解（P < 0.001）。总体而言，接受VSL#3和IBD治疗的14例患者中有3例（21.4%）以及接受安慰剂和IBD治疗的15例患者中有11例（73.3%）在随访1年内复发（P = 0.014；RR = 0.32；CI = 0.025 - 0.773；NNT = 2）。接受VSL#3治疗的所有3例患者以及接受安慰剂治疗的11例患者中有6例（54.5%）在诊断后6个月内复发。在6个月、12个月时或复发时，VSL#3组的内镜和组织学评分显著低于安慰剂组（P < 0.05）。未出现与VSL#3相关的生化或临床不良事件。
这是第一项针对儿童的随机、安慰剂对照试验，表明高浓度益生菌菌株混合物（VSL#3）在活动性UC中的疗效和安全性，并证明其在维持缓解中的作用。
