Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459

Dave Singh, Paul Cadden, Michael Hunter, Lisa Pearce Collins, Mike Perkins, Roy Pettipher, Elizabeth Townsend, Shân Vinall, Brian O'Connor

    Research output: Contribution to journalArticlepeer-review

    Abstract

    CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D2-driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients. A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days' treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study. There was a 25.4% (95% CI 5.1-45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p=0.002). PGD2-induced blood eosinophil shape change ex vivo was assessed at day 7 (n=7). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8- -0.4%; p=0.048). OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma. Copyright©ERS 2013.
    Original languageEnglish
    Pages (from-to)46-52
    Number of pages6
    JournalEuropean Respiratory Journal
    Volume41
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2013

    Keywords

    • Asthma
    • Chemokine
    • Eosinophil
    • Late allergic response

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