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]
Author:
Hisamatsu Tadakazu1, Matsumoto Takayuki2, Watanabe Kenji3, Nakase Hiroshi4, Motoya Satoshi5, Yoshimura Naoki6, Ishida Tetsuya7, Kato Shingo8, Nakagawa Tomoo9, Esaki Motohiro10, Nagahori Masakazu11, Matsui Toshiyuki12, Naito Yuji13, Kanai Takanori14, Suzuki Yasuo15, Nojima Masanori16, Watanabe Mamoru11, Hibi Toshifumi17, 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,
Affiliation:
1. The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan 2. Division of Gastroenterology, Department of Medicine, Iwate Medical University, Morioka, Japan 3. Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan 4. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan 5. Inflammatory Bowel Disease Center, Sapporo Kosei General Hospital, Sapporo, Japan 6. Department of Medicine, Division of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan 7. Ishida Clinic of IBD and Gastroenterology, Oita, Japan 8. Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan 9. Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan 10. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 11. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan 12. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan 13. Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan 14. Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan 15. Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan 16. Center for Translational Research, Institute of Medical Science Hospital, University of Tokyo, Tokyo, Japan 17. Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
Abstract
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.
Funder
Ministry of Health, Labour and Welfare of Japan
Publisher
Oxford University Press (OUP)
Subject
Gastroenterology,General Medicine
Cited by
17 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|