Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis

Yusuke Yoshimatsu, Makoto Naganuma, Shinya Sugimoto, Shun Tanemoto, Satoko Umeda, Tomohiro Fukuda, Ena Nomura, Kosuke Yoshida, Keiko Ono, Makoto Mutaguchi, Kosaku Nanki, Shinta Mizuno, Yohei Mikami, Kayoko Fukuhara, Tomohisa Sujino, Kaoru Takabayashi, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalDigestion
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Indigo Carmine
Suppositories
Ulcerative Colitis
Therapeutics
Rectum
Proctitis
Safety
Mesalamine
Aryl Hydrocarbon Receptors
Sigmoid Colon
Adrenal Cortex Hormones
Anti-Inflammatory Agents
Prospective Studies
Hemorrhage
Ligands
Inflammation
Pain

Keywords

  • Aryl hydrocarbon receptor
  • Indigo naturalis
  • Qing-dai
  • Suppository
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis. / Yoshimatsu, Yusuke; Naganuma, Makoto; Sugimoto, Shinya; Tanemoto, Shun; Umeda, Satoko; Fukuda, Tomohiro; Nomura, Ena; Yoshida, Kosuke; Ono, Keiko; Mutaguchi, Makoto; Nanki, Kosaku; Mizuno, Shinta; Mikami, Yohei; Fukuhara, Kayoko; Sujino, Tomohisa; Takabayashi, Kaoru; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori.

In: Digestion, 01.01.2019.

Research output: Contribution to journalArticle

Yoshimatsu, Yusuke ; Naganuma, Makoto ; Sugimoto, Shinya ; Tanemoto, Shun ; Umeda, Satoko ; Fukuda, Tomohiro ; Nomura, Ena ; Yoshida, Kosuke ; Ono, Keiko ; Mutaguchi, Makoto ; Nanki, Kosaku ; Mizuno, Shinta ; Mikami, Yohei ; Fukuhara, Kayoko ; Sujino, Tomohisa ; Takabayashi, Kaoru ; Ogata, Haruhiko ; Iwao, Yasushi ; Kanai, Takanori. / Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis. In: Digestion. 2019.
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abstract = "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.",
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AU - Yoshimatsu, Yusuke

AU - Naganuma, Makoto

AU - Sugimoto, Shinya

AU - Tanemoto, Shun

AU - Umeda, Satoko

AU - Fukuda, Tomohiro

AU - Nomura, Ena

AU - Yoshida, Kosuke

AU - Ono, Keiko

AU - Mutaguchi, Makoto

AU - Nanki, Kosaku

AU - Mizuno, Shinta

AU - Mikami, Yohei

AU - Fukuhara, Kayoko

AU - Sujino, Tomohisa

AU - Takabayashi, Kaoru

AU - Ogata, Haruhiko

AU - Iwao, Yasushi

AU - Kanai, Takanori

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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