Kenji Watanabe1, Takayuki Matsumoto2, Tadakazu Hisamatsu3, 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. Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address: ke-watanabe@hyo-med.ac.jp. 2. Division of Gastroenterology, Department of Medicine, Iwate Medical University, Morioka, Japan. 3. The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, 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, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan. 17. Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.
Abstract
BACKGROUND & AIMS: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. METHODS: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. RESULTS: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04-4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77-2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72-0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84-0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14-1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). CONCLUSIONS: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.
RCT Entities:
BACKGROUND & AIMS: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. METHODS: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. RESULTS: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04-4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77-2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72-0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84-0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14-1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). CONCLUSIONS: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.
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Authors: Philipp Schreiner; Markus F Neurath; Siew C Ng; Emad M El-Omar; Ala I Sharara; Taku Kobayashi; Tadakazu Hisamatsu; Toshifumi Hibi; Gerhard Rogler Journal: Inflamm Intest Dis Date: 2019-07-09