Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina; University of North Carolina Multidisciplinary Center for Inflammatory Bowel Diseases, Chapel Hill, North Carolina.
Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina; University of North Carolina Multidisciplinary Center for Inflammatory Bowel Diseases, Chapel Hill, North Carolina.
Gastroenterology. 2018 Oct;155(4):1098-1108.e9. doi: 10.1053/j.gastro.2018.06.046. Epub 2018 Jun 30.
BACKGROUND & AIMS: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC after induction therapy with methotrexate and steroids.
We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score of 6-12 with endoscopy subscore ≥ 2) despite previous conventional or biological therapy. The study comprised a 16-week open label methotrexate induction period followed by a 32-week double-blind, placebo-controlled maintenance period. Patients were given subcutaneous methotrexate (25 mg/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, n = 44) or were given placebo (n = 40) until week 48. We compared the efficacy of treatment by analyzing the proportion of patients who remained relapse free and were in remission at week 48 without use of steroids or other medications to control disease activity.
Ninety-one patients (51%) achieved response at week 16, and 84 patients were included in the maintenance period study. During this period, 60% of patients in the placebo group (24/40) and 66% in the methotrexate group (29/44) had a relapse of UC (P = .75). At week 48, 30% of patients in the placebo group (12/40) and 27% of patients in the methotrexate group (12/44) were in steroid-free clinical remission without need for additional therapies (P = .86). No new safety signals for methotrexate were detected.
Parenteral methotrexate (25 mg/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.
肠外甲氨蝶呤可诱导溃疡性结肠炎（UC）患者的临床缓解，但不能改善黏膜炎症的内镜下表现。我们进行了一项随机、安慰剂对照试验，以评估肠外甲氨蝶呤在诱导治疗后使用甲氨蝶呤和类固醇治疗的 UC 患者中维持无类固醇缓解或缓解的疗效。
我们进行了一项为期 48 周的试验，纳入了 179 名活动性 UC 患者（Mayo 评分 6-12 分，内镜下评分≥2 分），这些患者之前接受过常规或生物治疗。研究包括 16 周的开放性甲氨蝶呤诱导期和 32 周的双盲、安慰剂对照维持期。患者接受皮下甲氨蝶呤（25mg/周）和 12 周的类固醇减量。在第 16 周时，无类固醇应答的患者被随机分配到继续接受甲氨蝶呤（25mg/周，n=44）或接受安慰剂（n=40）治疗直至第 48 周的两组。我们通过分析第 48 周时无类固醇或其他药物控制疾病活动而不复发且处于缓解状态的患者比例来比较治疗效果。
91 名患者（51%）在第 16 周时达到缓解，84 名患者纳入维持期研究。在此期间，安慰剂组 60%（24/40）和甲氨蝶呤组 66%（29/44）的患者出现 UC 复发（P=0.75）。第 48 周时，安慰剂组 30%（12/40）和甲氨蝶呤组 27%（12/44）的患者无需额外治疗即可达到无类固醇的临床缓解（P=0.86）。未发现甲氨蝶呤的新安全性信号。
在诱导治疗期间达到无类固醇应答的患者中，每周 25mg 肠外甲氨蝶呤在预防 UC 复发方面并不优于安慰剂。临床试验.gov，编号：NCT01393405。
