Hanauer S B, Sandborn W J, Dallaire C, Archambault A, Yacyshyn B, Yeh C, Smith-Hall N
University of Chicago School of Medicine, Chicago, USA.
Can J Gastroenterol. 2007 Dec;21(12):827-34. doi: 10.1155/2007/862917.
Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.
A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline.
Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated.
Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.
已证明，每日口服2.4克至4.8克的缓释美沙拉嗪对轻至中度活动性溃疡性结肠炎（UC）有效，但对于轻至中度活动性UC患者以及中度疾病亚组患者，初始剂量4.8克/天是否比2.4克/天更有效尚不清楚。
一项为期六周的多中心、随机、双盲、对照试验（评估一种新剂量药物的安全性和临床疗效，即ASCEND I）将301例轻至中度活动性UC成人随机分为每日口服2.4克缓释美沙拉嗪组（400毫克片剂[n = 154]）或4.克/天组（800毫克片剂[n = 147]）。主要疗效终点为总体改善（即治疗成功），定义为从基线到第6周完全缓解或对治疗有反应。主要安全终点为不良事件和实验室评估。还对基线时中度UC患者的预先指定亚组进行了单独分析。
第6周时，治疗组之间的治疗成功率无统计学差异；每日接受2.4克缓释美沙拉嗪组的51%（150例中的77例）和接受4.8克/天组的56%（136例中的76例）达到疗效终点（P = 0.441）。然而，在中度疾病亚组中，较高的初始剂量更有效；每日给予2.4克缓释美沙拉嗪的患者中有57%（93例中的53例）和给予4.8克/天的患者中有72%（76例中的55例）实现了治疗成功（P = 0.0384）。两种治疗方案耐受性均良好。
缓释口服美沙拉嗪是轻至中度活动性UC患者有效且耐受性良好的初始治疗方法，与2.4克/天的美沙拉嗪相比，4.8克/天的剂量可能提高中度疾病患者的治疗成功率。
