The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study
| Autor: | Severine Vermeire, Julián Panés, Steven W. Martin, Ulrike Strauch, Gary Craig Burgess, Subrata Ghosh, Jana Sirotiakova, Jens Frederik Dahlerup, Wojciech Niezychowski, Jacqueline Spanton, Andreas Luegering |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty 610 Medizin Immunoglobulins Placebo Gastroenterology Inflammatory bowel disease Mucoproteins Double-Blind Method Internal medicine Cell Adhesion medicine Addressin Humans Lymphocytes Colitis Infusions Intravenous Retrospective Studies Integrin binding ddc:610 Immunity Cellular Dose-Response Relationship Drug biology business.industry Remission Induction Antibodies Monoclonal Colonoscopy Middle Aged Flow Cytometry medicine.disease Ulcerative colitis Faecal calprotectin Treatment Outcome Etrolizumab Immunology biology.protein Colitis Ulcerative Female business Cell Adhesion Molecules Follow-Up Studies |
| Zdroj: | Vermeire, S, Ghosh, S, Panes, J, Dahlerup, J F, Luegering, A, Sirotiakova, J, Strauch, U, Burgess, G, Spanton, J, Martin, S W & Niezychowski, W 2011, ' The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis : a randomised study ' Gut, vol. 60, no. 8, pp. 1068-75 . https://doi.org/10.1136/gut.2010.226548 |
| ISSN: | 0017-5749 |
| DOI: | 10.1136/gut.2010.226548 |
| Popis: | Background and aims Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis. Methods In this randomised, double-blind placebo-controlled study, 80 patients with active ulcerative colitis received single or multiple (three doses, 4-week intervals) doses of PF-00547,659 0.03–10 mg/kg IV / SC, or placebo. Safety was assessed by adverse events, laboratory tests, and immunogenicity. Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12. Faecal calprotectin was quantified as a measure of disease activity, and the number of α 4 β 7 + lymphocytes was measured to demonstrate drug activity. Results No obvious drug-related side effects were observed in the PF-00547,659 group, while patient numbers, especially those fully exposed, were small. Overall responder/remission rates at 4 and 12 weeks were 52%/13% and 42%/22%, respectively with combined PF-00547,659 doses compared with 32%/11% and 21%/0%, respectively with placebo. Equivalent endoscopic responder rates were 50% and 42% versus 26% and 29%, respectively. Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo (week 4: 63% vs 18%). Despite variability, there was a trend for an increase in α 4 β 7 + lymphocytes in patients receiving PF-00547,659. Conclusions The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials, to establish the role of PF-00547,659 in ulcerative colitis treatment. Trial Register No: NCT00928681. |
| Databáze: | OpenAIRE |
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