Harry Perkins Institute of Medical Research, School of Medicine and Pharmacology, University of Western Australia, Murdoch, WA, Australia; Centre for Inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, WA, Australia.
Harry Perkins Institute of Medical Research, School of Medicine and Pharmacology, University of Western Australia, Murdoch, WA, Australia.
Clin Gastroenterol Hepatol. 2017 Aug;15(8):1248-1255. doi: 10.1016/j.cgh.2017.02.027. Epub 2017 Mar 7.
BACKGROUND & AIMS: Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis.
Eleven patients received rectal tacrolimus (0.5 mg/mL), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo Clinic score.
A planned interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed because of ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8 of 11 patients receiving rectal tacrolimus and 1 of 10 patients receiving placebo (73% vs 10%; P = .004). Of the secondary endpoints, 5 patients with rectal tacrolimus achieved clinical remission compared with none receiving placebo (45% vs 0%; P = .015). Mucosal healing at Week 8 was achieved in 8 patients receiving rectal tacrolimus compared with 1 (73% vs 10%) receiving placebo (P = .004). The Inflammatory Bowel Disease Questionnaire increased ≥16 points over baseline in 5 of the tacrolimus and 2 (45% vs 20%) of the placebo patients (P = .36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared with placebo at Week 2 (4.3 ± 0.74 vs 5.8 ± 0.64; P = .15) and Week 4 (3.7 ± 0.96 vs 5.8 ± 0.6; P = .08) but was significantly lower at Week 8 (3.3 ± 1.2 vs 6.7 ± 0.62; P = .01). There were no safety issues identified with rectal tacrolimus use.
Rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis (Clinicaltrials.gov registration: NCT01418131).
难治性溃疡性直肠炎的治疗非常困难。局部给予他克莫司可能对治疗困难的直肠炎有效。这是一项在活动性溃疡性结肠炎患者中进行的随机、双盲、安慰剂对照的直肠他克莫司诱导试验。
11 名患者接受直肠他克莫司（0.5mg/ml），10 名患者接受安慰剂，治疗 8 周。主要终点是使用 Mayo 评分的临床反应。
在 20 名患者完成研究后进行的计划中期分析显示，两组之间存在显著差异，由于已招募的患者存在伦理问题，研究因伦理原因关闭，允许已入组的患者完成研究。主要终点在接受直肠他克莫司的 11 名患者中的 8 名和接受安慰剂的 10 名患者中的 1 名中得到满足（73%对 10%；P=0.004）。在次要终点方面，5 名接受直肠他克莫司治疗的患者达到临床缓解，而接受安慰剂的患者无一例达到（45%对 0%；P=0.015）。在 8 名接受直肠他克莫司治疗的患者中达到了 8 周时的黏膜愈合，而接受安慰剂的患者中只有 1 名（73%对 10%）（P=0.004）。在接受他克莫司治疗的患者中，有 5 名患者的炎症性肠病问卷（IBDQ）较基线增加≥16 分，而接受安慰剂的患者有 2 名（45%对 20%）（P=0.36）。最后，在第 2 周（4.3±0.74 对 5.8±0.64；P=0.15）和第 4 周（3.7±0.96 对 5.8±0.6；P=0.08），接受他克莫司治疗的患者的平均部分 Mayo 评分在数值上低于安慰剂组，但在第 8 周（3.3±1.2 对 6.7±0.62；P=0.01）时显著降低。使用直肠他克莫司未发现安全性问题。
直肠他克莫司在诱导难治性溃疡性直肠炎的临床反应、临床缓解和黏膜愈合方面比安慰剂更有效（Clinicaltrials.gov 注册号：NCT01418131）。
