Adrenomedullin for biologic‐resistant Crohn's disease: A randomized, double‐blind, placebo‐controlled phase 2a clinical trial
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- Toshihiro Kita
- Department of Projects Research, Frontier Science Research Center University of Miyazaki Miyazaki Japan
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- Shinya Ashizuka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine University of Miyazaki Miyazaki Japan
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- Teruyuki Takeda
- Department of Gastroenterology Fukuoka University Chikushi Hospital Fukuoka Japan
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- Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine Iwate Medical University Morioka Japan
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- Naoki Ohmiya
- Department of Gastroenterology Fujita Health University School of Medicine Toyoake Japan
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- Hiroshi Nakase
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
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- Satoshi Motoya
- IBD Center Sapporo Kosei General Hospital Hokkaido Japan
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- Hidehisa Ohi
- Department of Gastroenterology Idzuro Imamura Hospital Kagoshima Japan
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- Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine Kurume University School of Medicine Kurume Japan
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- Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology Kyorin University School of Medicine Mitaka Japan
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- Shuji Kanmura
- Digestive and Lifestyle Diseases Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
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- Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine Chiba University Chiba Japan
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- Shunji Ishihara
- Department of Gastroenterology Shimane University Hospital Izumo Japan
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- Masanao Nakamura
- Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine Nagoya Japan
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- Tomohiko Moriyama
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences Kyushu University Fukuoka Japan
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- Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
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- Ryoichi Nozaki
- Coloproctology Center Takano Hospital Kumamoto Japan
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- Shojiro Yamamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine University of Miyazaki Miyazaki Japan
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- Haruhiko Inatsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine University of Miyazaki Miyazaki Japan
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- Koji Watanabe
- Department of Projects Research, Frontier Science Research Center University of Miyazaki Miyazaki Japan
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- Kazuo Kitamura
- Department of Projects Research, Frontier Science Research Center University of Miyazaki Miyazaki Japan
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This was a multicenter, double‐blind, placebo‐controlled phase 2a trial that evaluated 24 patients with biologic‐resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin‐treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin‐treated groups at 24 weeks (<jats:italic>P</jats:italic> = 0.043) in the mixed‐effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In this trial, we observed a long‐lasting (24 weeks) decrease in CDAI in the adrenomedullin‐treated groups. Adrenomedullin might be beneficial for biologic‐resistant CD, but further research is needed.</jats:p></jats:sec>
収録刊行物
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- Journal of Gastroenterology and Hepatology
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Journal of Gastroenterology and Hepatology 37 (11), 2051-2059, 2022-07-25
Wiley