Vermeire, Severine and Ghosh, Subrata and Panes, Julian and Dahlerup, Jens F. and Luegering, Andreas and Sirotiakova, Jana and Strauch, Ulrike and Burgess, Gary and Spanton, Jacqueline and Martin, Steven W. and Niezychowski, Wojciech (2011) The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study. GUT, 60 (8). pp. 1068-1075. ISSN 0017-5749, 1468-3288
Full text not available from this repository. (Request a copy)Abstract
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 alpha(4)beta(+)(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 alpha(4)beta(+)(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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE CROHNS-DISEASE; HUMANIZED MONOCLONAL-ANTIBODY; MULTIPLE-SCLEROSIS; MAINTENANCE THERAPY; FECAL CALPROTECTIN; ALPHA-4 INTEGRIN; IN-VIVO; NATALIZUMAB; MADCAM-1; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jun 2020 04:54 |
| Last Modified: | 08 Jun 2020 04:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20515 |
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