Tadakazu Hisamatsu1, Takayuki Matsumoto2, Kenji Watanabe3, Hiroshi Nakase4, Satoshi Motoya5, Naoki Yoshimura6, Tetsuya Ishida7, Shingo Kato8, Tomoo Nakagawa9, Motohiro Esaki10, Masakazu Nagahori11, Toshiyuki Matsui12, Yuji Naito13, Takanori Kanai14, Yasuo Suzuki15, Masanori Nojima16, Mamoru Watanabe11, Toshifumi Hibi17. 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
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.
RCT Entities:
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.