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Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study

BACKGROUND/AIMS: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7(+) lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treat...

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Detalles Bibliográficos
Autores principales: Saruta, Masayuki, Park, Dong Il, Kim, Young-Ho, Yang, Suk-Kyun, Jang, Byung-Ik, Cheon, Jae Hee, Im, Jong Pil, Kanai, Takanori, Katsuno, Tatsuro, Ishiguro, Yoh, Nagaoka, Makoto, Isogawa, Naoki, Li, Yinhua, Banerjee, Anindita, Ahmad, Alaa, Hassan-Zahraee, Mina, Clare, Robert, Gorelick, Kenneth J., Cataldi, Fabio, Watanabe, Mamoru, Hibi, Toshifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Association for the Study of Intestinal Diseases 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000638/
https://www.ncbi.nlm.nih.gov/pubmed/32013314
http://dx.doi.org/10.5217/ir.2019.00039
Descripción
Sumario:BACKGROUND/AIMS: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7(+) lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). METHODS: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following 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) defined 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)