Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study
| العنوان: | Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study |
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| المؤلفون: | Toshifumi Hibi, Tatsuro Katsuno, Clare Robert A, J.P. Im, Kenneth J. Gorelick, Dong Il Park, Masayuki Saruta, Suk-Kyun Yang, Byung Ik Jang, Anindita Banerjee, Mina Hassan-Zahraee, Yinhua Li, Alaa Ahmad, Makoto Nagaoka, Takanori Kanai, Mamoru Watanabe, Fabio Cataldi, Jae Hee Cheon, Naoki Isogawa, Young-Ho Kim, Yoh Ishiguro |
| المصدر: | Intestinal Research, Vol 18, Iss 1, Pp 45-55 (2020) Intestinal Research |
| بيانات النشر: | Korean Association for the Study of Intestinal Diseases, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.medical_specialty, Population, lcsh:Medicine, Placebo, Gastroenterology, Pharmacokinetics, madcam, Internal medicine, Addressin, Clinical endpoint, Medicine, lcsh:RC799-869, education, Crohn's disease, Gastrointestinal tract, education.field_of_study, biology, business.industry, lcsh:R, japanese, pf-00547659, crohn disease, Inflammatory Bowel Diseases, medicine.disease, korean, biology.protein, Original Article, lcsh:Diseases of the digestive system. Gastroenterology, Antibody, business |
| الوصف: | Background/Aims: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAd CAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high af finity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). Methods: OPERA is a randomized, mul ticenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 fol lowing subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein >3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) de fined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509) (Intest Res 2020;18:45-55) |
| تدمد: | 2288-1956 1598-9100 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd2065c04e0f48b7ae4a06851da37adb https://doi.org/10.5217/ir.2019.00039 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bd2065c04e0f48b7ae4a06851da37adb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22881956 15989100 |
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