The University of Southampton
University of Southampton Institutional Repository

Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma

Norris, Virginia, Choong, Lee, Tran, Duyen, Corden, Zoe, Boyce, Malcom, Arshad, Hasan, Holgate, S., O'Connor, Brian, Millet, Sylvaine, Miller, Barry, Rohatagi, Shashank and Kirkesseli, Stephane (2005) Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma Journal of Allergy and Clinical Immunology, 116, (4), pp. 761-767. (doi:10.1016/j.jaci.2005.04.045).

Record type: Article

Abstract

Background: Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease.
Objective: We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation.
Methods: The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting ?2-agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting ?2-agonists, and asthma symptoms were recorded daily throughout the study.
Results: There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV1 from the prechallenge baseline (mean [SEM], ?81.99 [18.80] after IVL745 and ?72.58 [21.29] after placebo; 95% CI of difference, ?36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], ?23.44 [4.73] after IVL745 and ?21.30 [5.17] after placebo; 95% CI of difference, ?11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, ?13 to ?1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled ?2-agonist use, or PEF.
Conclusion: In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils.

Full text not available from this repository.

More information

Published date: 2005
Keywords: very late antigen (vla-4, ?4?1) antagonist, inhaled allergen challenge, late asthmatic response, eosinophil

Identifiers

Local EPrints ID: 27292
URI: http://eprints.soton.ac.uk/id/eprint/27292
ISSN: 0091-6749
PURE UUID: 4cea3359-e130-4645-aa4a-587e2bd1bc63

Catalogue record

Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:05

Export record

Altmetrics

Contributors

Author: Virginia Norris
Author: Lee Choong
Author: Duyen Tran
Author: Zoe Corden
Author: Malcom Boyce
Author: Hasan Arshad
Author: S. Holgate
Author: Brian O'Connor
Author: Sylvaine Millet
Author: Barry Miller
Author: Shashank Rohatagi
Author: Stephane Kirkesseli

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×