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The Effect of Inhaled Interferon-beta on Worsening of Asthma Symptoms Caused by Viral Infections: a Randomised Trial.
Am J Respir Crit Care Med. 2014 Jun 17;
Authors: Djukanović R, Harrison T, Johnston SL, Gabbay F, Wark P, Thomson NC, Niven R, Singh D, Reddel HK, Davies DE, Marsden R, Boxall C, Dudley S, Plagnol V, Holgate ST, Monk P
Abstract
Rationale Ex vivo asthmatic bronchial epithelial cells are more susceptible to rhinovirus infection due to deficient induction of the anti-viral protein, interferon-beta. Exogenous interferon-beta restores anti-viral activity. Objectives To compare the efficacy and safety of inhaled interferon-beta to placebo administered to asthmatic patients after onset of cold symptoms for the prevention or attenuation of asthma symptoms caused by respiratory viruses. Methods 147 asthmatics on inhaled corticosteroids (British Thoracic Society Steps 2-5), with a history of virus-associated exacerbations, underwent 14-day treatment with inhaled interferon-beta (n=72) or placebo (n=75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and anti-viral responses. Patients were randomised according to a pre-specified computer-generated schedule, stratified by site. Results 91% of randomised patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in 6-item Asthma Control Questionnaire <0.5) and interferon-beta treatment had no significant effect. However, in a subset of more difficult-to-treat, Step 4/5 asthmatics (n=27 interferon-beta; n=31 Placebo) Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by interferon-beta (p=0.004). Additionally, in the whole modified intention-to-treat population, interferon-beta enhanced morning peak expiratory flow recovery (p=0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarker responses. Interferon-beta was well tolerated. Conclusions This trial suggests that inhaled interferon-beta is a potential treatment for virus-induced exacerbations in difficult-to-treat asthmatics and justifies further, adequately powered, trials in this patient population. Trial registration ClinicalTrials.gov: NCT01126177 Funding Synairgen Research Limited, U.K.
PMID: 24937476 [PubMed - as supplied by publisher]