PT  - JOURNAL ARTICLE
AU  - Vermeire, Séverine
AU  - Ghosh, Subrata
AU  - Panes, Julian
AU  - Dahlerup, Jens F
AU  - Luegering, Andreas
AU  - Sirotiakova, Jana
AU  - Strauch, Ulrike
AU  - Burgess, Gary
AU  - Spanton, Jacqueline
AU  - Martin, Steven W
AU  - Niezychowski, Wojciech
TI  - The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study
AID  - 10.1136/gut.2010.226548
DP  - 2011 Aug 01
TA  - Gut
PG  - 1068--1075
VI  - 60
IP  - 8
4099  - http://gut.bmj.com/content/60/8/1068.short
4100  - http://gut.bmj.com/content/60/8/1068.full
SO  - Gut2011 Aug 01; 60
AB  - 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 α4β7+ 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 α4β7+ 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.