Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis
Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis
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DOI：
10.1159/000501152
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发表时间：
2019-06
期刊：
影响因子：
3.2
通讯作者：
Y. Yoshimatsu;M. Naganuma;S. Sugimoto;Shun Tanemoto;S. Umeda;T. Fukuda;E. Nomura;Kosuke Yoshida;K. Ono;M. Mutaguchi;K. Nanki;S. Mizuno;Y. Mikami;K. Fukuhara;T. Sujino;K. Takabayashi;H. Ogata;Y. Iwao;T. Kanai
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文献类型：
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作者：
Y. Yoshimatsu;M. Naganuma;S. Sugimoto;Shun Tanemoto;S. Umeda;T. Fukuda;E. Nomura;Kosuke Yoshida;K. Ono;M. Mutaguchi;K. Nanki;S. Mizuno;Y. Mikami;K. Fukuhara;T. Sujino;K. Takabayashi;H. Ogata;Y. Iwao;T. Kanai
背景：靛蓝天然靛蓝（IN）由芳烃受体的配体组成，并表现出抗炎作用。以前，我们证明了口服IN治疗8周可有效诱导溃疡性结肠炎（UC）患者的临床反应。一些患有直肠炎的UC患者对局部美沙拉嗪或皮质类固醇难以治疗，因此需要替代局部治疗。目的：我们的目的是前瞻性地评估在UC患者的安全性和有效性的栓剂。方法：我们于2018年2月至2018年10月进行了一项开放标签、单中心、前瞻性初步研究。共入组了10例活动性UC患者，这些患者从直肠到乙状结肠有中度至重度炎症。患者接受每日剂量50 mg IN栓剂，持续4周。主要终点是第4周的安全性。结果：虽然有1例患者出现肛门疼痛，但未观察到严重不良事件。在第4周，临床缓解率和粘膜愈合率分别为30%和40%。治疗后马约直肠出血分项评分显著改善（1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009）。基线直肠马约内镜分项评分（r-MES）为2分的患者中，约80%实现了粘膜愈合，但基线r-MES为3分的患者未实现粘膜愈合。结论：溃疡性结肠炎患者可以耐受4周的肠溶栓剂，但其疗效受病情严重程度的限制。需要进一步研究以确定UC患者的IN栓剂的最佳剂量。
Background: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. Objectives: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. Method: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. Results: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. Conclusions: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.