Sandborn William J, Regula Jaroslaw, Feagan Brian G, Belousova Elena, Jojic Njegica, Lukas Milan, Yacyshyn Bruce, Krzeski Piotr, Yeh Chyon-Hwa, Messer Christi A, Hanauer Stephen B
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Gastroenterology. 2009 Dec;137(6):1934-43.e1-3. doi: 10.1053/j.gastro.2009.08.069. Epub 2009 Sep 18.
It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC.
A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment.
The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events.
Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.
目前尚不清楚何种诱导剂量的美沙拉嗪对轻中度活动性溃疡性结肠炎（UC）患者最为有效。本研究旨在比较每日4.8克与2.4克美沙拉嗪治疗中度活动性UC的疗效和安全性。
开展了一项多中心、随机、双盲、为期6周的活性对照研究（ASCEND III），以评估772例中度活动性UC患者中，每日4.8克（Asacol HD，800毫克片剂；宝洁制药公司，俄亥俄州梅森）与每日2.4克（Asacol，400毫克片剂；宝洁制药公司）缓释美沙拉嗪的非劣效性。主要终点为第6周时的治疗成功（总体改善），定义为医生整体评估（基于直肠出血、大便频率和乙状结肠镜检查的临床评估）改善，且任何单项临床评估均未恶化。
达到了非劣效性的主要目标。接受每日4.8克美沙拉嗪治疗的患者中，70%（389例中的273例）在第6周时治疗成功，而接受每日2.4克治疗的患者为66%（383例中的251例）（每日2.4克减去每日4.8克的95%置信区间为-11.2至1.9）。此外，接受每日4.8克美沙拉嗪治疗的患者中，43%在第6周时实现临床缓解，而接受每日2.4克治疗的患者为35%（P = 0.04）。在先前接受过皮质类固醇、口服美沙拉嗪、直肠治疗或多种UC药物治疗的患者中，观察到每日4.8克剂量具有治疗优势。两种治疗方案耐受性均良好，不良事件相似。
每日4.8克（800毫克片剂）缓释美沙拉嗪对中度活动性UC患者有效且耐受性良好。
