The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study.
Gut
; 60(8): 1068-75, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21317177
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 α4ß7⺠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 α4ß7⺠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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inmunoglobulinas
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Colitis Ulcerosa
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Anticuerpos Monoclonales
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Mucoproteínas
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Gut
Año:
2011
Tipo del documento:
Article
País de afiliación:
Bélgica