Satoshi Tanida1, Nagamu Inoue2, Kiyonori Kobayashi3, Makoto Naganuma2, Fumihito Hirai4, Bunei Iizuka5, Kenji Watanabe6, Keiichi Mitsuyama7, Takuya Inoue8, Yoshiaki Ishigatsubo9, Yasuo Suzuki10, Masakazu Nagahori11, Satoshi Motoya12, Shiro Nakamura13, Vipin Arora14, Anne M Robinson14, Roopal B Thakkar14, Toshifumi Hibi15. 1. Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. 2. Keio University School of Medicine, Tokyo, Japan. 3. Kitasato University East Hospital, Kanagawa, Japan. 4. Fukuoka University Chikushi Hospital, Fukuoka, Japan. 5. Tokyo Women's Medical University, Tokyo, Japan. 6. Osaka City University Hospital, Osaka, Japan. 7. Kurume University School of Medicine, Kurume, Japan. 8. Osaka Medical College, Osaka, Japan. 9. Yokohama City University Graduate School of Medicine, Yokohama, Japan. 10. Toho University Medical Center Sakura Hospital, Chiba, Japan. 11. Tokyo Medical and Dental University, Tokyo, Japan. 12. IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan. 13. Hyogo College of Medicine, Hyogo, Japan. 14. AbbVie, North Chicago, Illinois. 15. Kitasato University Kitasato Institute Hospital, Tokyo, Japan. Electronic address: thibi@insti.kitasato-u.ac.jp.
Abstract
BACKGROUND & AIMS: Behçet's disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet's disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçet's disease who were refractory to corticosteroid and/or immunomodulator therapies. METHODS: The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçet's-related symptoms. RESULTS: Nine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed. CONCLUSIONS: Adalimumab is a potentially effective treatment for intestinal Behçet's disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.
BACKGROUND & AIMS: Behçet's disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet's disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçet's disease who were refractory to corticosteroid and/or immunomodulator therapies. METHODS: The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçet's-related symptoms. RESULTS: Nine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed. CONCLUSIONS:Adalimumab is a potentially effective treatment for intestinal Behçet's disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.
Authors: Stephan R Vavricka; Alain Schoepfer; Michael Scharl; Peter L Lakatos; Alexander Navarini; Gerhard Rogler Journal: Inflamm Bowel Dis Date: 2015-08 Impact factor: 5.325