Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Inflamm Bowel Dis. 2013 Aug;19(9):1889-95. doi: 10.1097/MIB.0b013e31828ef13f.
Endoscopic recurrence occurs in up to 80% of patients with Crohn's disease 1 year after intestinal resection. Imidazole antibiotics, thiopurines, and particularly their combination have proven efficacy in preventing endoscopic recurrence. The aim of the study was to compare the efficacy of the addition of metronidazole (for 3 months after the surgical treatment) to azathioprine for the prevention of postsurgical endoscopic recurrence.
A pilot study was made of 50 patients with Crohn's disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year. The patients were randomized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months (n = 25 per arm). Endoscopic assessment was performed 6 and 12 months after the surgical resection. The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of <2 at 6 months. The initial sample size had an 80% statistical power in detecting an absolute risk reduction of ≥30%.
Endoscopic recurrence occurred in 28% and 44% of the patients at 6 months (P = 0.19) and in 36% and 56% (P = 0.15) at 12 months in the metronidazole and placebo groups, respectively. No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence (Rutgeerts score ≥ 3) at 6 and 12 months. Likewise, there were no differences in the rate of adverse events between the treatment groups.
The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence beyond azathioprine alone in this study but does not worsen its safety profile.
克罗恩病患者在肠切除术后 1 年内，内镜复发率高达 80%。咪唑类抗生素、硫嘌呤，特别是它们的联合应用，已被证明在预防内镜复发方面具有疗效。本研究旨在比较在硫嘌呤治疗的基础上加用甲硝唑（术后 3 个月）预防术后内镜复发的疗效。
对 50 例行回肠结肠吻合术的克罗恩病患者进行了一项试点研究，这些患者术后每天接受 2 至 2.5mg/kg 的硫嘌呤治疗 1 年。患者被随机分为两组，分别接受每天 15 至 20mg/kg 的甲硝唑或安慰剂治疗 3 个月（每组 n = 25）。在术后 6 个月和 12 个月进行内镜评估。主要终点是在 6 个月时根据 Rutgeerts 评分<2 定义的内镜复发的预防。初始样本量具有 80%的统计学效能，可检测到≥30%的绝对风险降低。
在 6 个月时，甲硝唑组和安慰剂组的内镜复发率分别为 28%和 44%（P = 0.19），在 12 个月时分别为 36%和 56%（P = 0.15）。在治疗组之间，6 个月和 12 个月时严重内镜复发（Rutgeerts 评分≥3）的发生率无统计学差异。同样，两组之间不良反应发生率也无差异。
在本研究中，甲硝唑联合硫嘌呤并未显著降低内镜复发的风险，超过了单独使用硫嘌呤，但并未增加其安全性。
