TY - JOUR T1 - Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial JF - Thorax JO - Thorax DO - 10.1136/thoraxjnl-2021-217429 SP - thoraxjnl-2021-217429 AU - Hugo Farne AU - Nicholas Glanville AU - Nicholas Johnson AU - Tata Kebadze AU - Julia Aniscenko AU - Eteri Regis AU - Jie Zhu AU - Maria-Belen Trujillo-Torralbo AU - Onn Min Kon AU - Patrick Mallia AU - A Toby Prevost AU - Michael R Edwards AU - Sebastian L Johnston AU - Aran Singanayagam AU - David J Jackson Y1 - 2021/10/29 UR - http://thorax.bmj.com/content/early/2021/12/06/thoraxjnl-2021-217429.abstract N2 - Background and aims The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.Methods Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.Results Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0–14 (difference 3.0 (95% CI −29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.Conclusion Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.Data are available upon reasonable request. Anonymised data are available on reasonable request from the corresponding author, Professor Sebastian Johnston. ER -