Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

Tadakazu Hisamatsu; Takayuki Matsumoto; Kenji Watanabe; Hiroshi Nakase; Satoshi Motoya; Naoki Yoshimura; Tetsuya Ishida; Shingo Kato; Tomoo Nakagawa; Motohiro Esaki; Masakazu Nagahori; Toshiyuki Matsui; Yuji Naito; Takanori Kanai; Yasuo Suzuki; Masanori Nojima; Mamoru Watanabe; Toshifumi Hibi; Akira Andoh; Toshifumi Ashida; Katsuya Endo; Yutaka Endo; Hiroshi Fujita; Mikihiro Fujiya; Ken Haruma; Sakiko Hiraoka; Ichiro Hirata; Yutaka Honda; Hideki Iijima; Bunei Iizuka; Kentaro Ikeya; Takuya Inoue; Syuji Inoue; Yo Ishiguro; Shunji Ishihara; Hiroaki Ito; Ryuichi Iwakiri; Takashi Kagaya; Hiroshi Kashida; Jun Kato; Takehiko Katsurada; Fukunori Kinjyo; Kiyonori Kobayashi; Mayumi Kodama; Reiko Kunisaki; Koichi Kurahara; Takafumi Kurokami; Lee Kyouwon; Koichiro Matsuda; Kazuhiro Matsueda; Keiichi Mitsuyama; Yuji Mizokami; Shiro Nakamura; Masafumi Nomura; Atsuhiro Ogawa; Kazuichi Okazaki; Kazuaki Otsuka; Hirotake Sakuraba; Masayuki Saruta; Makoto Sasaki; Takayuki Shirai; Tomoaki Suga; Kazuhito Sugimura; Toshiro Sugiyama; Fuminao Takeshima; Hiroyuki Tamaki; Shinji Tanaka; Satoshi Tanida; Keiichi Tominaga; Taku Tomizawa; Syojiro Yamamoto; Masaki Yamashita; Atsushi Yoshida

doi:10.1093/ecco-jcc/jjz030

Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

Tadakazu Hisamatsu, Takayuki Matsumoto, Kenji Watanabe, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, Akira Andoh, Toshifumi AshidaKatsuya Endo, Yutaka Endo, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Sakiko Hiraoka, Ichiro Hirata, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Syuji Inoue, Yo Ishiguro, Shunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Hiroshi Kashida, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Keiichi Mitsuyama, Yuji Mizokami, Shiro Nakamura, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Syojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida

Department of Internal Medicine (Gastroenterology and Hepatology)

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

Original language	English
Pages (from-to)	1097-1104
Number of pages	8
Journal	Journal of Crohn's and Colitis
Volume	13
Issue number	9
DOIs	https://doi.org/10.1093/ecco-jcc/jjz030
Publication status	Published - 2019 Sept 1

Keywords

Adalimumab
Crohn's disease
anti-TNF-alpha antibody
thiopurine

ASJC Scopus subject areas

Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hisamatsu, T., Matsumoto, T., Watanabe, K., Nakase, H., Motoya, S., Yoshimura, N., Ishida, T., Kato, S., Nakagawa, T., Esaki, M., Nagahori, M., Matsui, T., Naito, Y., Kanai, T., Suzuki, Y., Nojima, M., Watanabe, M., Hibi, T., Andoh, A., ... Yoshida, A. (2019). Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]. Journal of Crohn's and Colitis, 13(9), 1097-1104. https://doi.org/10.1093/ecco-jcc/jjz030

Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease : A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]. / Hisamatsu, Tadakazu; Matsumoto, Takayuki; Watanabe, Kenji et al.

In: Journal of Crohn's and Colitis, Vol. 13, No. 9, 01.09.2019, p. 1097-1104.

Research output: Contribution to journal › Article › peer-review

Hisamatsu, T, Matsumoto, T, Watanabe, K, Nakase, H, Motoya, S, Yoshimura, N, Ishida, T, Kato, S, Nakagawa, T, Esaki, M, Nagahori, M, Matsui, T, Naito, Y, Kanai, T, Suzuki, Y, Nojima, M, Watanabe, M, Hibi, T, Andoh, A, Ashida, T, Endo, K, Endo, Y, Fujita, H, Fujiya, M, Haruma, K, Hiraoka, S, Hirata, I, Honda, Y, Iijima, H, Iizuka, B, Ikeya, K, Inoue, T, Inoue, S, Ishiguro, Y, Ishihara, S, Ito, H, Iwakiri, R, Kagaya, T, Kashida, H, Kato, J, Katsurada, T, Kinjyo, F, Kobayashi, K, Kodama, M, Kunisaki, R, Kurahara, K, Kurokami, T, Kyouwon, L, Matsuda, K, Matsueda, K, Mitsuyama, K, Mizokami, Y, Nakamura, S, Nomura, M, Ogawa, A, Okazaki, K, Otsuka, K, Sakuraba, H, Saruta, M, Sasaki, M, Shirai, T, Suga, T, Sugimura, K, Sugiyama, T, Takeshima, F, Tamaki, H, Tanaka, S, Tanida, S, Tominaga, K, Tomizawa, T, Yamamoto, S, Yamashita, M & Yoshida, A 2019, 'Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]', Journal of Crohn's and Colitis, vol. 13, no. 9, pp. 1097-1104. https://doi.org/10.1093/ecco-jcc/jjz030

Hisamatsu T, Matsumoto T, Watanabe K, Nakase H, Motoya S, Yoshimura N et al. Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]. Journal of Crohn's and Colitis. 2019 Sept 1;13(9):1097-1104. doi: 10.1093/ecco-jcc/jjz030

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title = "Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]",

abstract = "Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.",

keywords = "Adalimumab, Crohn's disease, anti-TNF-alpha antibody, thiopurine",

author = "Tadakazu Hisamatsu and Takayuki Matsumoto and Kenji Watanabe and Hiroshi Nakase and Satoshi Motoya and Naoki Yoshimura and Tetsuya Ishida and Shingo Kato and Tomoo Nakagawa and Motohiro Esaki and Masakazu Nagahori and Toshiyuki Matsui and Yuji Naito and Takanori Kanai and Yasuo Suzuki and Masanori Nojima and Mamoru Watanabe and Toshifumi Hibi and Akira Andoh and Toshifumi Ashida and Katsuya Endo and Yutaka Endo and Hiroshi Fujita and Mikihiro Fujiya and Ken Haruma and Sakiko Hiraoka and Ichiro Hirata and Yutaka Honda and Hideki Iijima and Bunei Iizuka and Kentaro Ikeya and Takuya Inoue and Syuji Inoue and Yo Ishiguro and Shunji Ishihara and Hiroaki Ito and Ryuichi Iwakiri and Takashi Kagaya and Hiroshi Kashida and Jun Kato and Takehiko Katsurada and Fukunori Kinjyo and Kiyonori Kobayashi and Mayumi Kodama and Reiko Kunisaki and Koichi Kurahara and Takafumi Kurokami and Lee Kyouwon and Koichiro Matsuda and Kazuhiro Matsueda and Keiichi Mitsuyama and Yuji Mizokami and Shiro Nakamura and Masafumi Nomura and Atsuhiro Ogawa and Kazuichi Okazaki and Kazuaki Otsuka and Hirotake Sakuraba and Masayuki Saruta and Makoto Sasaki and Takayuki Shirai and Tomoaki Suga and Kazuhito Sugimura and Toshiro Sugiyama and Fuminao Takeshima and Hiroyuki Tamaki and Shinji Tanaka and Satoshi Tanida and Keiichi Tominaga and Taku Tomizawa and Syojiro Yamamoto and Masaki Yamashita and Atsushi Yoshida",

year = "2019",

month = sep,

day = "1",

doi = "10.1093/ecco-jcc/jjz030",

language = "English",

volume = "13",

pages = "1097--1104",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Elsevier",

number = "9",

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TY - JOUR

T1 - Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease

T2 - A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

AU - Hisamatsu, Tadakazu

AU - Matsumoto, Takayuki

AU - Watanabe, Kenji

AU - Nakase, Hiroshi

AU - Motoya, Satoshi

AU - Yoshimura, Naoki

AU - Ishida, Tetsuya

AU - Kato, Shingo

AU - Nakagawa, Tomoo

AU - Esaki, Motohiro

AU - Nagahori, Masakazu

AU - Matsui, Toshiyuki

AU - Naito, Yuji

AU - Kanai, Takanori

AU - Suzuki, Yasuo

AU - Nojima, Masanori

AU - Watanabe, Mamoru

AU - Hibi, Toshifumi

AU - Andoh, Akira

AU - Ashida, Toshifumi

AU - Endo, Katsuya

AU - Endo, Yutaka

AU - Fujita, Hiroshi

AU - Fujiya, Mikihiro

AU - Haruma, Ken

AU - Hiraoka, Sakiko

AU - Hirata, Ichiro

AU - Honda, Yutaka

AU - Iijima, Hideki

AU - Iizuka, Bunei

AU - Ikeya, Kentaro

AU - Inoue, Takuya

AU - Inoue, Syuji

AU - Ishiguro, Yo

AU - Ishihara, Shunji

AU - Ito, Hiroaki

AU - Iwakiri, Ryuichi

AU - Kagaya, Takashi

AU - Kashida, Hiroshi

AU - Kato, Jun

AU - Katsurada, Takehiko

AU - Kinjyo, Fukunori

AU - Kobayashi, Kiyonori

AU - Kodama, Mayumi

AU - Kunisaki, Reiko

AU - Kurahara, Koichi

AU - Kurokami, Takafumi

AU - Kyouwon, Lee

AU - Matsuda, Koichiro

AU - Matsueda, Kazuhiro

AU - Mitsuyama, Keiichi

AU - Mizokami, Yuji

AU - Nakamura, Shiro

AU - Nomura, Masafumi

AU - Ogawa, Atsuhiro

AU - Okazaki, Kazuichi

AU - Otsuka, Kazuaki

AU - Sakuraba, Hirotake

AU - Saruta, Masayuki

AU - Sasaki, Makoto

AU - Shirai, Takayuki

AU - Suga, Tomoaki

AU - Sugimura, Kazuhito

AU - Sugiyama, Toshiro

AU - Takeshima, Fuminao

AU - Tamaki, Hiroyuki

AU - Tanaka, Shinji

AU - Tanida, Satoshi

AU - Tominaga, Keiichi

AU - Tomizawa, Taku

AU - Yamamoto, Syojiro

AU - Yamashita, Masaki

AU - Yoshida, Atsushi

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

AB - Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

KW - Adalimumab

KW - Crohn's disease

KW - anti-TNF-alpha antibody

KW - thiopurine

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U2 - 10.1093/ecco-jcc/jjz030

DO - 10.1093/ecco-jcc/jjz030

M3 - Article

C2 - 30753377

AN - SCOPUS:85063364840

SN - 1873-9946

VL - 13

SP - 1097

EP - 1104

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 9

ER -

Concerns and Side Effects of Azathioprine during Adalimumab Induction and Maintenance Therapy for Japanese Patients with Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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