Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis: A Double-Blind Placebo-Controlled Multicenter Trial
Newly Developed Antibiotic Combination Therapy for Ulcerative Colitis: A Double-Blind Placebo-Controlled Multicenter Trial
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DOI：
10.1038/ajg.2010.84
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发表时间：
2010-08-01
影响因子：
9.8
通讯作者：
Sato, Nobuhiro
中科院分区：
文献类型：
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作者：
Ohkusa, Toshifumi;Kato, Kimitoshi;Sato, Nobuhiro
目的：多样梭杆菌可能导致溃疡性结肠炎（UC）。我们进行了一项双盲安慰剂对照多中心试验，以确定抗生素联合治疗是否诱导和/或维持活动性UC的缓解。方法：慢性轻至重度复发性UC患者随机分为阿莫西林1500 mg/天、四环素1500 mg/天、甲硝唑750 mg/天口服组和安慰剂组，随访2周。主要研究终点是临床反应（治疗完成后3个月的Mayo评分），次要终点是12个月的临床和内镜评分改善。Anti-F。酶联免疫吸附法测定各种抗体。结果：治疗组和安慰剂组各有105名受试者。在主要终点，抗生素组的缓解率显著高于安慰剂组（44.8% vs 22.8%, P = 0.0011）。内镜评分在3个月时显著改善（P = 0.002与安慰剂相比）。3个月时缓解率为19.0%（抗生素）vs 15.8%（安慰剂）（P = 0.59）。在次要终点，抗生素组的缓解率显著高于安慰剂组（分别为49.5%和21.8%,P < 0.0001）。内窥镜评分在抗生素治疗后12个月显著提高（P = 0.002 vs安慰剂）。12个月时，抗生素组的缓解率为26.7%，安慰剂组为14.9% （P = 0.041）。有反应者抗体滴度下降，无反应者抗体滴度下降，抗生素组抗体滴度高于安慰剂组。更多的预处理类固醇依赖UC患者在治疗完成后停止使用皮质类固醇（6个月：分别为28.6%对11.8%,P = 0.046； 9个月：分别为34.7%对13.7%,P = 0.019； 12个月：分别为34.7对13.7%,P = 0.019）。这些影响在活跃组（Mayo评分为6-12）的亚分析中比在总病例（0-12）的亚分析中更大。未发生严重的药物相关毒性。结论：与安慰剂相比，2周的三联抗生素治疗对活动性UC的改善、缓解和类固醇戒断更有效。
OBJECTIVES: Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.METHODS: Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.RESULTS: Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P = 0.0011). Endoscopic scores significantly improved at 3 months (P = 0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P = 0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P < 0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P = 0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P = 0.041). F. varium antibody titers decreased in responders but not in non-responders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P = 0.046; 9 months: 34.7 vs. 13.7%, respectively, P = 0.019; and 12 months: 34.7 vs. 13.7%, respectively, P = 0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred.CONCLUSIONS: The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.