TY - JOUR
T1 - Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis
T2 - a post hoc analysis from the INDIGO study
AU - For the INDIGO Study Group
AU - Naganuma, Makoto
AU - Sugimoto, Shinya
AU - Fukuda, Tomohiro
AU - Mitsuyama, Keiichi
AU - Kobayashi, Taku
AU - Yoshimura, Naoki
AU - Ohi, Hidehisa
AU - Tanaka, Shinji
AU - Andoh, Akira
AU - Ohmiya, Naoki
AU - Saigusa, Keiichiro
AU - Yamamoto, Takayuki
AU - Morohoshi, Yuichi
AU - Ichikawa, Hitoshi
AU - Matsuoka, Katsuyoshi
AU - Hisamatsu, Tadakazu
AU - Watanabe, Kenji
AU - Mizuno, Shinta
AU - Abe, Takayuki
AU - Suzuki, Yasuo
AU - Kanai, Takanori
AU - Naganuma, Makoto
AU - Nakazato, Yoshihiro
AU - Teratani, Toshiaki
AU - Ogata, Haruhiko
AU - Iwao, Yasushi
AU - Yamasaki, Hiroshi
AU - Toyonaga, Takahiko
AU - Nakano, Masaru
AU - Hibi, Toshifumi
AU - Sameshima, Yoichi
AU - Hayashi, Ryohei
AU - Ueno, Yoshitaka
AU - Bamba, Shigeki
AU - Watanabe, Mamoru
AU - Nakazawa, Atsushi
AU - Koike, Yuji
AU - Imai, Jin
AU - Shimoyama, Takahiro
AU - Takeuchi, Ken
AU - Nagasaka, Mitsuo
AU - Kitano, Atsuo
AU - Ashizuka, Shinya
AU - Inatsu, Haruhiko
AU - Onodera, Kei
AU - Nakase, Hiroshi
AU - Kitamura, Kazuya
AU - Ikeya, Kentaro
AU - Hanai, Hiroyuki
AU - Suda, Wataru
N1 - Funding Information:
This study was funded by Keio Fukuzawa Memorial Fund.
Funding Information:
This study was supported in part by grants from the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research (to M. Naganuma). We would like to thank Editage ( www.editage.jp ) for English language editing.
Funding Information:
Makoto Naganuma received commercial research funding from EA Pharma Co., Ltd. and Mochida Pharmaceutical Co., Ltd., outside the submitted work. Taku Kobayashi received advisory fee from Alfresa Pharma, Covidien, Eli Lilly Japan K.K, Ferring Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Thermo Fisher Scientific Inc. and received lecture fees from Mitsubishi Tanabe Pharma Corp., AbbVie GK, Kyorin Pharmaceutical Co., Ltd., Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd. Zeria Pharmaceutical Co., Ltd., Astellas Pharma Inc., Mochida Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Asahi Kasei Medical Co., Ltd., Alfresa Pharma, Ezai Pharmaceutical Co., Ltd., Gilead, Janssen Pharmaceutical K.K., and received commercial research funding from EA Pharma Co., Ltd., Thermo Fisher Scientific Inc., Alfresa Pharma, Asahi Kasei Medical Co., Ltd. Nippon Kayaku Co., outside the submitted work. Naoki Yoshimura received lecture fees from Mitsubishi Tanabe Pharma Corp., AbbVie GK, and Mochida Pharmaceutical Co., Ltd., outside the submitted work. Naoki Omiya received lecture fees from Mylan EPD and commercial research funding from Mylan EPD, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K, Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., outside the submitted work. Yasuo Suzuki received lecture fees from Mitsubishi Tanabe Pharma Corp., Mochida Pharmaceutical Co., Ltd., AbbVie GK, Zeria Pharmaceutical co., Ltd., Kyorin Pharmaceutical Co., Ltd. Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., EA Pharma Co., Ltd. and research grants from Mitsubishi Tanabe Pharma Corp. and AbbVie GK, EA Pharma Co., Ltd. Kissei Pharma Co., Ltd., JIMRO Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., outside the submitted work. Tadakazu Hisamatsu received lecture fees from AbbVie GK, EA pharma Co., Ltd., Eisai Co., Ltd., JIMRO Co., Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd. Mochida Pharmaceutical Co., Ltd., and research grants from AbbVie GK, Asahi Kasei Medical Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd, Mochida Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd., outside the submitted work. Takanori Kanai received lecture fees from Mitsubishi Tanabe Pharma Corp, Astellas Pharma Inc, Miyarisan Pharmaceutical Co., Ltd. AstraZeneca Plc, EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., grants from AbbVie GK, Mochida Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp, Takeda Pharmaceutical Co., Ltd., Nihon Kayaku, Yakult Honsha Co., Ltd., Zeria Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Ezaki Glico Co., Ltd. JIMRO Co., Ltd., EN Otsuka Pharmaceutical Co., Ltd., outside the submitted work. All other authors have no competing interests to declare.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Background: We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness. Methods: In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5–2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8. Results: The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8. Conclusions: In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.
AB - Background: We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness. Methods: In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5–2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8. Results: The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8. Conclusions: In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.
KW - Anti-TNFa treatment
KW - Indigo naturalis
KW - Steroid dependent
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85073819029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073819029&partnerID=8YFLogxK
U2 - 10.1007/s00535-019-01625-2
DO - 10.1007/s00535-019-01625-2
M3 - Article
C2 - 31529220
AN - SCOPUS:85073819029
VL - 55
SP - 169
EP - 180
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 2
ER -