Hanauer S, Schwartz J, Robinson M, Roufail W, Arora S, Cello J, Safdi M
University of Chicago School of Medicine, Illinois.
Am J Gastroenterol. 1993 Aug;88(8):1188-97.
The efficacy of a capsule formulation of mesalamine was assessed in 374 patients with mild to moderately active ulcerative colitis. Patients, stratified to pancolitis or left-sided disease, received either placebo or mesalamine at 1, 2, or 4 g daily for 8 wk. Efficacy was assessed using clinical improvement--physician global assessment, sigmoidoscopic index, biopsy score, trips to the toilet, and clinical symptoms (abdominal pain, urgency, stool consistency, and rectal bleeding)--and induction of remission (more stringent criteria for physician global assessment, sigmoidoscopic index, and biopsy score). For physician global assessment of treatment benefit, 79% and 84% of patients on the 2-g and 4-g doses of mesalamine, respectively, received treatment benefit, compared with 54% on placebo (p < or = 0.0002). For the physician global assessment of treatment success, both the 2-g and 4-g doses of mesalamine were superior to placebo (57% and 59% of patients, p = 0.0021 and 0.0012, respectively), compared with 36% on placebo. Both the 2-g and 4-g doses produced statistically significant macroscopic (endoscopic) improvement compared with placebo (p < 0.004). The 4-g dose also produced a statistically significant microscopic (histologic) improvement compared to placebo (p < 0.002). Significant improvement compared to placebo was also observed at 2 g and 4 g for the four clinical symptoms and trips to the toilet (p < or = 0.003). Oral mesalamine capsules were significantly superior to placebo for inducing remission, with 29% of patients at 2 g and 29% at 4 g achieving remission by physician global assessment, compared with 12% on placebo. Forty-four percent and 48% of patients receiving 2 g and 4 g of mesalamine, respectively, achieved remission by sigmoidoscopic index (p < 0.05), compared with 31% on placebo. Thirty-nine percent of patients at 4 g daily achieved microscopic remission, compared with 23% on placebo (p < 0.03). Treatment response was not affected by extent of disease or prior steroid or sulfasalazine therapy. These data suggest that controlled-release mesalamine capsules are a safe and effective monotherapy in doses of 2-4 g daily for treating mild to moderately active ulcerative colitis, as well as for inducing remission, regardless of prior oral steroid or sulfasalazine therapy or extent of disease.
对374例轻至中度活动性溃疡性结肠炎患者评估了美沙拉嗪胶囊制剂的疗效。患者按全结肠炎或左侧病变分层，接受安慰剂或每日1g、2g或4g美沙拉嗪治疗，疗程8周。采用临床改善情况（医生整体评估、乙状结肠镜检查指数、活检评分、排便次数及临床症状，如腹痛、便急、大便性状及直肠出血）及缓解诱导情况（对医生整体评估、乙状结肠镜检查指数及活检评分采用更严格标准）评估疗效。对于医生对治疗益处的整体评估，服用2g和4g剂量美沙拉嗪的患者分别有79%和84%获得治疗益处，而服用安慰剂的患者为54%（p≤0.0002）。对于医生对治疗成功的整体评估，2g和4g剂量的美沙拉嗪均优于安慰剂（患者分别为57%和59%，p分别为0.0021和0.0012），而服用安慰剂的患者为36%。与安慰剂相比，2g和4g剂量均使宏观（内镜）改善具有统计学意义（p<0.004）。4g剂量与安慰剂相比还使微观（组织学）改善具有统计学意义（p<0.002）。2g和4g剂量在四项临床症状及排便次数方面与安慰剂相比也有显著改善（p≤0.003）。口服美沙拉嗪胶囊在诱导缓解方面显著优于安慰剂，按医生整体评估，服用2g的患者中有29%、服用4g的患者中有29%实现缓解，而服用安慰剂的患者为12%。接受2g和4g美沙拉嗪的患者分别有44%和48%按乙状结肠镜检查指数实现缓解（p<0.05），而服用安慰剂的患者为31%。每日服用4g的患者中有39%实现微观缓解，而服用安慰剂的患者为23%（p<0.03）。治疗反应不受疾病范围或既往类固醇或柳氮磺胺吡啶治疗的影响。这些数据表明，控释美沙拉嗪胶囊作为一种安全有效的单一疗法，每日剂量2 - 4g，可用于治疗轻至中度活动性溃疡性结肠炎以及诱导缓解，无论既往口服类固醇或柳氮磺胺吡啶治疗情况或疾病范围如何。
