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]
Authors: Hisamatsu Tadakazu , Matsumoto Takayuki , Watanabe Kenji , Nakase Hiroshi , Motoya Satoshi , Yoshimura Naoki , Ishida Tetsuya , Kato Shingo , Nakagawa Tomoo , Esaki Motohiro , Nagahori Masakazu , Matsui Toshiyuki , Naito Yuji , Kanai Takanori , Suzuki Yasuo , Nojima Masanori , Watanabe Mamoru , Hibi Toshifumi ,   DIAMOND study group, Andoh Akira , Ashida Toshifumi , Endo Katsuya , Endo Yutaka , Esaki Motohiro , Fujita Hiroshi , Fujiya Mikihiro , Haruma Ken , Hibi Toshifumi , Hiraoka Sakiko , Hirata Ichiro , Hisamatsu Tadakazu , Honda Yutaka , Iijima Hideki , Iizuka Bunei , Ikeya Kentaro , Inoue Takuya , Inoue Syuji , Ishida Tetsuya , Ishiguro Yo , Ishihara Shunji , Ito Hiroaki , Iwakiri Ryuichi , Kagaya Takashi , Kanai Takanori , Kashida Hiroshi , Kato Shingo , Kato Jun , Katsurada Takehiko , Kinjyo Fukunori , Kobayashi Kiyonori , Kodama Mayumi , Kunisaki Reiko , Kurahara Koichi , Kurokami Takafumi , Kyouwon Lee , Matsuda Koichiro , Matsueda Kazuhiro , Matsui Toshiyuki , Matsumoto Takayuki , Mitsuyama Keiichi , Mizokami Yuji , Motoya Satoshi , Naito Yuji , Nakagawa Tomoo , Nakamura Shiro , Nakase Hiroshi , Nojima Masanori , Nomura Masafumi , Ogawa Atsuhiro , Okazaki Kazuichi , Otsuka Kazuaki , Sakuraba Hirotake , Saruta Masayuki , Sasaki Makoto , Shirai Takayuki , Suga Tomoaki , Sugimura Kazuhito , Sugiyama Toshiro , Suzuki Yasuo , Takeshima Fuminao , Tamaki Hiroyuki , Tanaka Shinji , Tanida Satoshi , Tominaga Keiichi , Tomizawa Taku , Watanabe Kenji , Watanabe Mamoru , Watanabe Kenji , Yamamoto Syojiro , Yamashita Masaki , Yoshida Atsushi , Yoshimura Naoki 
Published: January 2019

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.